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Endocrine
Block 4
238
Medical
Graduate
03/03/2009

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Term
integument
Definition
largest and most visble organ of the body; consists of the skin and epidermal derivatives such as hair, nails, and glands
Term
functions of the skin
Definition
1. protection to microorganisms, temperatures and UV radiation; 2. water barrier-prevents drying and loss of H2O through evaporation; 3. regulation of body temp conservation and dissipation of heat; 4. excretion of salts; 5. synthesis of vitamin D; 6. sensory organ that identifies pain, texture, shape, and temp
Term
components of the skin
Definition
surface epithelium (epidermis) and underlying bed of CT called the dermis; epidermis is keratinized stratified squamous epithelium and dermis is dense irregular CT
Term
epidermis
Definition
outermost layer of the skin, avascular and prominent cell is keratinocyte and it is multiplayered
Term
stratum basale
Definition
deepest layer of epidermis conisists of a single layer of cuboidal cells which are held together by desmosomes and attached to basal lamina by hemi-desmosomes; cells are dividing and are responsible for regeneration of cells of epidermis
Term
melanocytes
Definition
non-epidermal cells derived from neural crest origin; lack desmosomes; have melanosomes that contain melanin and these granules are distributed along cytoplasmic processes to surrounding keratinocytes
Term
formation of melanin
Definition
formed by complex set of steps where tyrosine is converted to DOPA by the enzyme tyrosinase which DOPA is then converted to melanin-most abundant in st. basale b/c cells are dividing continuously and needed to protect nucleus; pigmentation due to # and size of melanosome
Term
stratum spinosum
Definition
several layers thick and keratinocytes are large and polygonal and have increased numbers of desmosomes and tonofilaments; cells produce membrane-coating granules with single membrane and have lamellate appearance and contatin lipid-rich material
Term
Langerhans cells
Definition
star shaped cells found in st. spinosum do not associate with keratinocytes not identifible with H&E staining; closely resemble macrophages in antigen presenting-once come into contact with antigen they migrate to regional lymph nodes
Term
stratum granulosum
Definition
consists of 1-5 layers of flattened polygonal cells; have two types of granules keratohyalin granules and membrane coating granule; vitamin D production occurs in this layer and loss of cellular organelles occurs
Term
keratohyalin granules
Definition
not located in membrane bound organelles but forms free accumulations in cytoplasm of cells giving rise to amorphous matrix fills spaces between them and binds together the tonofilaments in the cells of st. corneum
Term
membrane-coating granule
Definition
fuses with plasma membrane and releases lipid rich content and filling interstitial space and making it impermeable to water
Term
stratum lucidum
Definition
present only in thick skin consists of several layers of flattened dead cells; lack of complements of organelles and usually translucent
Term
stratum corneum
Definition
cells completely filled with keratin filaments embedded in a dense matrix of proteins; nuclei are no longer indentifiable, cells are very flat and space between the cells have been filled with lipids and cell envelope becomes thick making the cell resistant to water
Term
differences between thick and thin skin
Definition
thick skin has st. lucidum and a larger st spinosum and much thicker st. corneum
Term
dermis characteristics
Definition
assumes functions of thermoregulation and supports vascular netword to supply avascular epidermis with nutrients; consists mostly of fibroblasts responsible for secreting collagen, elastin, and ground substance and immune cells are present
Term
junction between epidermis and dermis
Definition
not straight but undulates; epidermal rete ridge is epidermis projecting into dermis and dermal papilla is dermis projecting into the epidermis; increase area of contact between the layers of skin
Term
papillary layer
Definition
part of dermis forming dermal papilla; have thinner LCT, collagenous fibers and contains capillaries and nerves
Term
reticular layer
Definition
much thicker contain DCT bundles of collagen, larger BV Av anastomoses; more thick collagen and more elastic fibers; mechanical strength, sensory perception and elasticity
Term
Meissner's corpuscles
Definition
found in papillary layer are tactile receptors for texture and shape found in dermal papilla-wrapped in Schwann cells and upcapsulated in CT and unmylinated nerve ending
Term
merkel disc
Definition
st. basale layer loses myelin sheath and goes through basal lamina and acts as tactile receptor
Term
Pacinian corpuscles
Definition
encapsulated nerve ending found in dermis and hypodermis senses pressure and vibration; the inner lamellae are schwann cells and outer lamellae are from fibroblast cells and collagen fibrils
Term
subcutaneous layer
Definition
contains LICT and fat in which ducts and secretory portions of the swear glands, nerve, mammary glands, and roots of hair are found
Term
hair characteristics
Definition
elongated keratinized structures derived from invaginations of epidermal epithelium has a shaft which projects above the surface of the skin and root which lies beneath the surface of the skin and enclosed by a hair follicle
Term
hair follicle
Definition
expanded at its base and this expansion is called hair bulb; epithelial root sheath is a derivative of epidermis and has outer root sheath-continuation of skin st basale and st spinosum; inner root sheath is keratinized sheath that arises from the cell of the hair matrix; connective tissue sheath arises from the dermis contains sensory nerves that wraps aroundepithelial root sheath
Term
hair bulb
Definition
new hair cells are produced by the cells of the hair bulb that sits on the dermis and hair aquires melanin and become keratinized; hair papilla highly cellular CT filling indentation of the hair bulb and it is rich in cell, capillaires, and nerve fibers and contains melanocytes influences hair growth
Term
sebaceous glands
Definition
typically associated with hair follicles, has short, wide, unbranched excretory duct lined with stratified squamous epithelium; secretory portion is solid mass of cells and basal cells undergo mitosis and daughter cells become filled with lipid and new cells push older cells towards center; cells produce oily sebum consisting of lipids, TGs and cell debris and secrete by holocrine (entire cell is lost)-lubricates the skin and inflammation results in acne
Term
eccine sweat gland
Definition
portion of duct lying in the dermis and in the subcutaneous layer is lined by stratified cubodial; secretory portion is lined by simple cubodial to simple columnar epithelium containing two types of cells; 1. clear cells involved in ion and water transport and dark cellscontains organelles including secretory granules associated with protein synthesis; contractile myoepithelial cells lie between the bottoms of the secretory cells and basal lamina helps expel the excretory product
Term
sweat
Definition
made by the eccine sweat gland contains electrolyte, urea and released by merocrine mode of secretion; plays importatn role in temp regulation and minor excretory organ
Term
nails
Definition
includes nail plate and nail bed; nail plate has body and root of the nail and is compact layer of keratinized cells modified st cornuem filled with keratin; nail bed made up of epidermis and dermis lies beneath the nail plate-involved in nail growth undergo mitosis adding new cells to the nail plate which undergo keratinination
Term
vitamin A active substances
Definition
compounds other than carotenoids which exhibit biochemical activities of retinol include retinol, retinal, and retinoic acid
Term
retinoid
Definition
generic term includes both naturally occurring vitamin A active substances and compounds that synthetic analogues of retinol, retinal, or retinoic acid
Term
absorption of vitamin A
Definition
absorbed by the small intestine in form of retinol and converted into retinyl esters with palmitic acid within the intestinal mucosa-the REs are packaged into chylomicrons the chylomicron remnants then go to the liver for processing
Term
dietary souces of vitamin
Definition
major one is beta-carotene present in many vegetables and egg yolks and it is cleaved into two molecule of retinal and these are reduced to retinol; second source is retinyl esters found in animal products including milk and meat these are hydrolyzed in intestinal lumen to retinol and absorbed in jejunem
Term
retinol metabolism in the liver
Definition
retinyl esters are hydrolyzed to retinol and it can either be reesterfied and stored in the liver or transported to target cells in body bound to retinol binding protein (RBP); storage of retnyl ester occurs in stellate cells
Term
RBP
Definition
synthesized and secreted with a molecule of retinol bound by the hepatocytes and it binds to another plasma protein tranthyretin (TTR) binds one molecule of RBP also plays a role in binding T4 molecule; binding to TTR prevent glomerular filtration and prevents loss of retinol
Term
uptake of retinol by target cells
Definition
RBP and TTR are not taken up by the cell and the retinol binds to a cellular retinol binding protein where it can be oxidized to retinal and then retinoic acid (retinal to retinoic acid is not reversible) retinoic acid binds to CRABP which enters the nucleus and has role in regulation of gene expression; the retinoic acid can be oxidized to inactivate it so it can be excreted
Term
effects of only ingesting retinoic acid
Definition
causes night blindness due to lack of 9-cis retinal and male animals will be sterile because retinoic acid cannot be transported across the blood-testes barrier
Term
visual cycle and role of retinol
Definition
all trans retinol enters the retinal pigment epithelial cells where it is isomerized and can be stored as retnyl ester or oxidized to 11-cis retinal and then it is transported into neural retina where it combines with opsin to form rhodopsin which combines with light to generate the nerve impulse and form alltrans retinal which is reduced to retinol
Term
differentiation and maintainance of epithelial cells
Definition
functions in all epithelial tissues of the body defiency of vit A results in transformation of simple columnar into pseudostratified and stratified epithelium and eventually to keratinizing stratified squamous epithelium-without vit A the cornea has lesions that cause its destruction and cause permanent blindness (xerophthalmia)
Term
mechanism of action of retinoic acid
Definition
there are two types of receptors RAR (retinoic acid receptors) binds both all trans and 9-cis retinoic acid and RXR which binds only 9-cis retinoic acid when liganded these receptors bind as heterodimers to regulatory sequences called retinoic response elements
Term
vitamin A deficiency and toxicity
Definition
nightblindness is first sign followed by xerophyhalmia and diminished ability to fight infection; toxicity includes nausea, vomiting, headache, blurred vision, dizziness, loss of muscular coordination and death
Term
DiGeorge syndrome
Definition
constellation of congenital defects consisiting of facial defects, heart defects, hypoparathyroidism, cognitive, behavioral, and emotional problems; absence of thymus and parathyroid on chromosome CATCH-22
Term
development of pharyngeal arches
Definition
occurs at 5 weeks
Term
ectodermal derivatives of pituitary gland
Definition
1. diverticulum from stomadeum that move upward toward the forebrain (Rathke's pouch) moved dorsally and superiorly from extoderm of oral cavity; 2. at 5 weeks of development down growth from the developing diencephalon (caudal region of the forebrain) known as infundibulum and grows towards Rathke's pouch
Term
development of Rathke's pouch
Definition
gives rise to the anterior pituitary (pars distalis) and pars tuberalis which will eventually surround the infundibulum
Term
development infundibulum
Definition
gives rise to the pars intermedia and posterior pituitary (pars nervosa)
Term
pituitary development
Definition
develops through the 2nd and 3rd month of gestation; ACTH hormone is detected at 8 weeks; LH/FSH at 10 weeks as is GH; hypothamico-hypophyseal portal system not established until week 12
Term
parathyroid development
Definition
involves pharyngeal arches develop from endoderm of 3rd and 4th arches; inferior parathyroids arise from divertulosis of third pouch at around 5 weeks and detach and descend to inferior pole of thyroid gland around 5 weeks of gestation; superior parathyroids develop from fourth pouch a week after inferior parathyroids and detach and descend to superior pole of the thyroid gland position by week 7 of gestation
Term
thyroid development
Definition
diverticulum from the foramen cecum (midline structure from development of tongue) located between tuberculum impar and the hypobranchial eminence and the cells descend in front of the pharynx and remains in contact with the pharynx by narrow duct called thyroglossal duct and it descend to region of junction of trachea and larynx
Term
parafollicular cells
Definition
aka C cells arise from 4th pouch and produce calcitonin and migrate to the thyroid
Term
adrenal glands development
Definition
interaction of coelomic epithelial cells (arising from anterior to metanephric duct) migrating to above the developing kidney and neural crest cells from region of sympathetic ganglia; starting 6 weeks; epithelial cells become cortex and neural crest cells become medulla (2nd month of gestation
Term
neural crest cells in region of sympathetic chain
Definition
under FGF2 and neural growth factor will become sympathetic neurons but under the effect of glucocorticoids become chromaffin cells of adrenal medulla
Term
inner adrenal cortex
Definition
80% of fetal adrenal makes dehydroepiandrosterone which is converted to estrogen in fetal liver and placenta
Term
endocrine tissues
Definition
may occur as discrete organs or scattered masses of cells like islets of Langerhans; or individual cells diffusely distributed throughout organs in GI tract
Term
organization of endocrine glands
Definition
have simple microscopic structure mostly cells with little stroma and cells are often large and polyhedral and arranged in cords or plates with delicate CT investment; have extensive blood supply and products secreted directly into circulation by fenestrated capillaries
Term
hormonal functions
Definition
integrate many functions of the body maintain homeostasis as well as complex body processes such as ovarian/uterine cycles and they influence behavior
Term
clearance of hormones
Definition
excreted, degraded or rendered biologically inactive by liver or kidney
Term
components from the oral ectoderm in hypophysis
Definition
called adenohypophysis include pars tuberalis, pars distalis, and pars intermedia
Term
neural ectoderm of hypophysis
Definition
neurohypophysis include pars nervosa, infundibular stalk and medium eminence of tuber cinereum
Term
pars distalis
Definition
major division of adenohypophysis and produces several hormones and most cells produce a cell specific hormone sotred in secretory granule
Term
chromophiles
Definition
stain well and there are two kinds one contains granules that stain blue and are called basophils; the other has granules that stain red and are called acidophils; have abundant RER, well-developed golgi and immature and mature secretory granules and produce protein hormones
Term
types of acidophils
Definition
one makes growth hormone and the other makes prolactin
Term
types of basophils
Definition
thyroid stimulating hormone (TSH); adrenocorticotropic hormone (ACTH); follicle stimulating hormone (FSH); and luteinizing hormone (LH)
Term
chromophobes
Definition
contain few secretory granules and thought to respresent degranulated chromophils
Term
pars intermedia
Definition
located between the pars distalis and the pars nervosa consists mainly of basophils; and colloid cysts are sometimes present; cells that produce melanocyte-stimulating hormone (MSH) ACTH and beta-endorphin and beta lipotropin (LPH)
Term
pars tuberalis
Definition
wraps around the infundibular stalk has mostly basophils which in some species contain LH
Term
regulation of release of pars distalis
Definition
occurs when substances are received from the median eminance/hypothalamus and are called releasing or releasing-inhibiting hormones
Term
releasing hormones
Definition
include tyrotropin-releasing hormone (TRH); GnRH- stimulates release of LH and FSH; and ACTH releasing hormone
Term
release-inhibiting hormones
Definition
there are active on prolactin and GH cells and these cells also have releasing hormone
Term
location of hypothalamus
Definition
found surrounding 3rd ventricle and its medial surfaces are adjacent to 3rd ventricle
Term
hypophyseal portal system
Definition
releasing hormones are synthesized in cell bodies of neurosecretory neurons in the hypothalamus and packaged in neurosecretory granules and these move down the axon to terminal which lie near fenestrated capillaries of primary capillary plexus travel in the hypophyseal portal cessels to reach the secondary capillary plexus in par distalis and reacts with cells of hormone and causes their release
Term
neurohypophysis
Definition
median eminence, infundibular stalk and par nervosa (release oxytocin and ADH)
Term
oxytocin
Definition
main effect is to cause smooth muscle and myoepithelial cells to contract; it is involved in milk let down reflex
Term
antidiuretic hormone
Definition
effect on tubules in kidney causing them to become permeable to water and water reabsorbed in the body or can cause raise in blood pressure
Term
pars nervosa
Definition
consists of unmyelinated nerve fibers and pituicytes (glial cells) axons of neurosecretory neurons located in the hypothalamus specifically in supraoptic nucleus and paraventricular nucleus axons pass through infundibular stalk to pars nervosa where they end on or near fenestrated capillaries form hypothalamo-hypophyseal tract
Term
herring bodies
Definition
enlargements of axon terminals because of storage of secretory granules
Term
four basic mechanisms for intercellular communication
Definition
1. endocrine-hormone is secreted into blood; 2. paracrine-hormone has effect locally on adjacent target cells; 3. autocrine-hormone has effect on target sites on the same cell; 4. contact-dependent-have a signaling cell and target cell and a membrane bound signal elicits the effect
Term
structural classses of hormones
Definition
1. peptides/proteins-3 to 100s of amino acids and may have sugar moeities; 2. steroid related-small and hydrophilic; 3. amines-all derivatives from tyrosine and includes thyroid hormones T3 and T4
Term
peptide hormone synthesis
Definition
precursor hormones are not active are pre-prohormone with signal sequence which is cleaved in ER and forms prohormone-packages into secretory granules and stored until the cell receives a signal to release it
Term
steroid hormone biosynthesis
Definition
derived from cholesterol (27C) and ratelimiting step is P450scc that converts it to pregnenolone (21C) by side chain cleavage; forms progesterone (21) to form androgens (19) by P450c17 which is converted to testosterone which is further cleaved by aromatase-CYP19 to make estrogen (18); progesterone converted to mineral corticoids and glucocorticoids; not easily stored and so release regulated by enzymes in pathway (phosphorylation and expression regulation)
Term
way hormones exert their biological effects
Definition
interact with receptors on target cells and this interaction is highly specific and has high affinity; small amounts have biological effect because of the highly affinity and another similar hormone can cause effect if in high enough concentration because of specificity but takes a lot
Term
classes of receptors
Definition
1. steroid-related receptors-lipid soluble, has carrier protein, has a longer half life, is intracellular and the cellular mediator is the receptor-hormone complex; 2. peptide,catecholamines-water soluble, no carrier protein, half life only minutes, receptor is on the cell surface and effects mediated by a 2nd messenger
Term
peptide hormone signaling
Definition
hormone binds on cell surface receptor as first messagener; and second message is from conformational changes in receptor causes changes within the cell
Term
G protein coupled signalling
Definition
there are three subunits and the trimer is inactive and the alpha subunit has a GTPase which is inactive with GDP and active with GTP and it dissociates from beta and gamma subunits and alters activities of enzymes and ion channels; beta/gamma subunit can also have cellular/protein activity effects
Term
cAMP second messenger
Definition
the G protein activates adenylate cyclase which takes ATP to form cAMP (like in glucagon) and then activatice PKA which activates many proteins; other receptors can activative cAMP to increase effects; theres rapid signal termination by degrading cAMP and changing to GDP to turn off adenylate cyclase activity and phosphatases removes the phosphate groups from the proteins
Term
IP3/Ca/DAG second messenger system
Definition
g protein activates phospholipase C which cleaves PIP to IP3 and DAG; the IP3 causes Ca release from the SR/ER and the DAG activates PKC to cause cellular response
Term
ion channels in signalling release
Definition
Ca channels directly regulate cytosolic Ca levels and K channels indirectly regulate Ca levels by hyperpolarizing membrane and inactivating Ca channels; in beta cells ATP in activates K channel which hyperpolarize membrane but when ATP levels increase the K channel inhibited and Vm depolarizes and Ca channels open and cytosolic Ca high and stimulates insulin release
Term
steroid hormone action
Definition
nuclear receptors inside the cell bind to DNA regulate transcription of genes by stimulating or inhibiting and only free hormone can enter the cell but carrier proteins can regulate the steroid hormone potency
Term
steroid hormone nuclear receptors
Definition
common features include DNA binding domain zinc fingers, hormone binding domain, transactivating domain, receptor dimers
Term
hormone levels
Definition
they fluctuate can be episodic-includes suckling, food intake, or exercise; circadian-24 hour cycle; pulsatile-periodicity less than 24 hrs
Term
degradation of peptide hormones
Definition
due to proteases in blood, proteases in the cell surface, and receptor mediated endocytosis-where clathrin coated pits formed and peptide hormones degraded in lysosomes receptors recycled to cell surface
Term
permphigus foliaceus
Definition
bullous rash on skin risk factors include pesticides, malignancy (cancer), pharmaceuticals, hormones, infectious agents, gastronomy, UV light, and stress autoimmune disease where desmoglein 1 is attacked by antibodies and causes sloughing of the skin; much worse with vulgaris which is 1 and 3; treatment includes topical steroids or oral; immunosuppresent; antiTNFalpha agents and CD20 against B cells
Term
desmoglein family
Definition
intracellular proteins involved in desmosomes and interaction with tonofilaments; mouth expresses more 3 and skin expresses more 1 and 1 is expressed closer to the surface in st. corneum and 3 is expressed closer to st. spinosum
Term
TRH
Definition
first hypothalamic hormone is a three amino acid hormone made of glutamate, histidine, and prolinamide
Term
hypothalamic hormones
Definition
peptide hormones that are produced and released from neurons usually modified at the C and N terminus; the modifications used are required for biological activity and also protect against proteolysis
Term
lactotropes
Definition
there is no stimulating hormone from the hypothalamus and is under tonic inhbition from PIH (DOPA) from the hypothalamus
Term
biological roles of hypothalamic/anterior pitiutary axis
Definition
can either have direct biological effects as with GH and prolactin or cause other endocrine organs to release a hormone
Term
glycoprotein family of anterior pituitary hormones
Definition
includes TSH, LH, and FSH contain different sugar moieties to confer specificity; has two subunits alpha and beta and both are required for activity but the beta subunit confers specificity and alpha subunits are similar so adding B subunit to another alpha subunit (TSH+LH) will be active for LH
Term
POMC family of anterior pitiutary hormones
Definition
POMC is cleaved to ATCH and B-LPH; the ACTH can be cleave to alpha-MSH and CLIP and the B-LPH can be cleaved to B-endorphins
Term
increased ACTH
Definition
believed that people with excess ACTH people can get hyperpigmentation because of it being cleaved to form alpha-MSH (melanocyte stimulating hormone)
Term
structure of prolactin and growth hormone
Definition
have similar structure but at physiological levels do not bind to the others receptors
Term
factors that effect GH secretion
Definition
1. neurogenic-occurs during stages III and IV of sleep, stress and dopamine agonists; 2.hormonal-GHRH stimulates (somatocrinin) and GHRIH inhibits (somatostaitin), IGF-1 level, estrogen/testosterone and T3/T4 required; 3.metabolic-amino acids-stimulate, decreasing FAs stimulates; hypoglycemia stimulates and hyperglycemia inhibits to maintain sugar protein levels so cells can grow
Term
measurement of abnormal GH
Definition
so in excess GH want to give glucose and see the effect of GH release if have elevated GH will not decrease levels with hyperglycemia; if child is not growing can check by having the child fast, exercise or use amino acids and see if GH increases
Term
effects of GH
Definition
stimulates liver to release IGF1 and gluconeogenesis and glycogen synthesis; growth plate for growth; adipose tissue-lipolysis; muscle-decreases glucose uptake and increases protein synthesis
Term
production and actions of IGF1
Definition
GH binds to liver receptors which stimulates IGF synthesis which IGF causes other tissues to grow
Term
effect of growth hormone on bone
Definition
GH binds to receptors on prechondrocyte causing differentiation and proliferation and near the diaphysis it becomes calcified and it eventually catches up with epiphysis and fuses causing cessation of growth
Term
regulation of GH secretion
Definition
factors cause hypothalamus to secrete GHRH to stimulate ant pitiutary to release GH which binds to liver and causes synthesis of IGF and IGF has feedback inhibition to decrease GHRH and increase somatostatin release to inhibit GH release
Term
synthesis of post pituitary hormones
Definition
synthesized in hypothalamus and OT is synthesized primarily in paraventricular nucleus and VP primarily produced in the supraoptic nucleus and neurons are specific for a given hormone
Term
mechanism for VP release from a neuron
Definition
vasopressonergic neuron gets signal action potential travels to nerve terminus and depolarization opens Ca channels which causes vesicles of VP to be exocytosed and the membrane recaptures the vesicle and the granules enter the blood stream
Term
structure of OT and VP
Definition
both are cyclic nonapeptides and both amidated at the C terminus, differ only by two amino acids and these differences confer specificity and VP contains Arg at position 8 and only active VP in human
Term
vasopressin receptors
Definition
V2 receptor is in kidney principal cell where its cAMP mediated effect is water reabsorption; V1 receptors have a IP3/DAG effect in ant pituitary and vascualr smooth muscle to produce ACTH and vasoconstriction
Term
oxytocin V1 receptor
Definition
effect in mammary myoeptithelium to contract myoepithelia; uterine myometrium-uterine contraction; corpus luteum-inhibit progesterone production; all mediated by IP3/DAG secondary messenger
Term
synthesis of VP and OT
Definition
both synthesized as pre-prohormones and both have neurophysin that is needed for correct processing and folding I (OT) and II (VP)
Term
vasopressin release
Definition
regulated by signals related to osmolality of ECF and it functions to decrease osmolality and a 2% increase in osmolality will stimulate osmoreceptors and 10-15% decrease in BP will stimulate release from low blood pressure receptors in atrium and pulmonary vessels
Term
action of VP on kidney collecting duct
Definition
binds to V2 receptor and stimulates cAMP which causes insertion of AQP2 vesicles into luminal membrane and increases H2O permeability across the membrane
Term
regulation of oxytocin release
Definition
suckling stimulates OT release to contract myoepithelia and milk ejection; stimulates uterine contractions and progesterone inhibits OT and estrogen stimulates and cervical distension stimulates OT and estrogen also increase receptors in myometrium for OT; concentration of receptors change during pregnancy and they peak at the time of labor and mammmary gland OT receptors peak during lactation; but hypophysectimized females have normal delivery because uterine might produce OT
Term
clinical importance of ocytocin
Definition
administered to induce labor and after birth OT maintains uterine contraction which prevents excessive bleeding from the uterus and saves the mother; OT antagonists are being used to prevent pre-term labor
Term
clinical importance of vasopressin
Definition
diabetes insipidus causes excessive thirst and urination due to inadequeate secretion or utilization of vasopressin; due to physical damage to pituitary stalk or brain tumors; or neurogenic DI caused by vasopressin deficiency (mutations in neurophysin II) or nephrogenic DI-kidneys are resitant to VP mutations to V2 receptors or mutations in APQ2 channel
Term
radio immunoassay
Definition
use non covalent long lived interaction (Kd=equilibrium constant=affinity small Kd=high affinity) competitive inhibition assay a radiolabeled hormone binds to antibody and measure the amount of hormone bound vs standard to determine concentration of serum hormone; the unlabeled OT displaces the radioactive OT and use linear portion of standard curve to determine serum concentration; hormone must be less that antibodies and takes a lot of time
Term
immunometric assay
Definition
increases hormone sensitivity and two Abs for the hormone are used and the first is unlabeled and should be in excess and coupled to solid support; and second Ab linked to a probe (fluorescent, enxyme, or radiolabeled) and this must be much greated than the concentration of the hormone; greater the color the greater amount of hormone and enables us to measure intact active hormones
Term
functions of ion channels
Definition
functions in selective, rapid ion diffusion and allows for gating between permeant and impermeant states (from voltage/ligand binding)
Term
selected ion flux
Definition
determines the Eion and hence Em and as Ca moves into cell it leave negative charge outside the cell so the membrane depolarizes; reverse happens with K channels and usually sets the resting membrane potential of most cells
Term
mechanisms for rapid Ca diffusion into the cytosol
Definition
Ca channels in the ER/SR by IP3 gated channels and RYR channels in SR; Ca permenant channels in plasma membranes (voltage gated Ca channels)
Term
Ca release through IP3 gated Ca channels in the ER
Definition
binds to receptor causes PLC to cleave to IP3 and DAG and IP3 binds to gated channels on ER and releases Ca in cytosol
Term
Ca release through voltage gated channels
Definition
signal arises from AP and causes membrane to depolarize and opens the Ca channel and causes the Ca to go inside from outside
Term
cytosolic Ca effectors
Definition
regulates enzymes, ion channels, and excytotic proteins; TnC and calmodulin (present in all eukaroyic cells) has 4 high affinity subunits that have cooperativity in binding of Ca; synaptoagmin is Ca effector that mediates exocytosis
Term
potassium channels regulating cytosolic Ca levels
Definition
hyperpolarize membrane and inactivate voltage gated ca channels and when inhibited the membrane depolarizes and Ca channels are activated; there is much diversity of K channels
Term
regulation of PRL release
Definition
dopamine and GPCR is inhibitory and Gia activated and GB/gamma and Kir channel interact and Ca channel inactivated by hyperpolarization and cytosolic Ca decreases and decrease in PRL exocytosis and Gialpha inhibit AC decreasing cAMP and PRL mRNA; estrogen uncouples Gialpha and Kir channels less active and membrane depolarized
Term
roles of Ca in mediating cell functions
Definition
contraction of muscle, neurotransmitter release and nerve transmission, secretion of peptides from cells, mediating actions of many hormones, regulation of enzyme activity, and structural role in bone
Term
regulation of PTH
Definition
keeps ECF levels of Ca high acts directly on kidney and bone and indirectly on gut-stimulates Ca reabsorption, inhibits Pi resorption in kidney and stimulates Ca resorption in bone and stimulates formation of active vit D
Term
biosynthesis and secretion of PTH
Definition
high Ca inhibits PTH release; binds receptor and G protein inhibits cAMP and inhibits PTH release and Galphaq stimulates cytosolic Ca; acute low Ca no cAMP inhibition and increase PTH release and chronic low Ca stimulates transcription; no Ca to inhibit release of vesicles
Term
relationship between plasma Ca and PTH secretion
Definition
max PTH at low Ca but there is a limit and but there is still a finite amount of PTH released that Ca cannot completely inhibit
Term
effects of PTH on kidney
Definition
increase Ca reabsorption in distal tubule by stimulating GPCR and cAMP/PKA and stimulates luminal insertion of Ca channels and in BL membranes stimulates NXC and CaATPase (net flux from lumen to blood); proximal tubule cell inhibits phosphate reabsorption by stimulating Na/Pi contransporter endocytosis also stimulates 1a-hyrdoxylase (rate limiting step in vit D synthesis)
Term
bone remodeling
Definition
PTH/vitD stimulates osteoblasts which secrete paracrines and cytokines to stimulate osteoclast differentiation to resorb bone
Term
differentiation and activation of osteoclasts
Definition
requires contact between osteoclasts and osteoblasts; osteoclasts express M-CSF and RANK receptors and osteoblasts secrete M-CSF and express RANKL (membrane bound cytokine); OPG inhibits osteoclast activation and neutralizes RANKL
Term
effects of PTH and Vit D on bone resorption
Definition
stimulate osteoblasts to release cytokines that stimulate recruitment of osteoclast precursors and the osteoclasts secrete acid and endopeptidases in ruffled border; calcitonin causes osteoclasts to dedifferentiate
Term
effects of sex steroids on bone resorption
Definition
estrogens inhibit cytokine release from osteoblasts and stimulate OPG release after menopause ovaries dont produce estrogen and increased cytokine release and higher osteoclast activity and osteoporosis
Term
ruffled border of osteoclasts
Definition
erode bone matrix by release of H+ by generation from carbonic anhydrase and it is pumped out and integrins keep H high y sealing ruffled border (bisphosphanates disrupt integrin interaction)
Term
biosynthesis of vit D
Definition
requires UV light; 7DHcholesterol has ring opened by the light and is hydroxylated to form 25-OH-D3 which has high affinity for carrier protein and is reacted to form 1,25-OH2-D3 by 1a-hydroxylase in proximal tubule of kidney and has low affinity for carrier protein and eventually inactivated to calcitroic acid
Term
actions of vitamin D
Definition
calcitrol-VDR receptor stimulates gene expression increasing number of proteins-Ca channels in intestinal cells increasing epithelial Ca channel and CaT1 transporter and Na/PO4 transporter to bring Ca and binds to calbindin which keeps Ca low in the cell to shuttle Ca to blood side to keep Ca low and increase absrorption
Term
thyroid general characteristics
Definition
hormones regulate the rate of metabolism of the body and control calcium levels in the blood; arise from the floor of the mouth (endoderm) and produces-T4 (thyroxine) and triiodothyronine (T3) which regulate and calcitonin involved in regulating calcium in the blood; thyroid sequesters iodine from the blood for use with T3 and T4
Term
principle thyroid cells
Definition
follicular epithelial cells arranged in a single layer around a central cavity that contatin colloid, gel-like storage material; these together consistitute a thyroid follicle; the height of these cells depends on the functional state of the cell with them being taller when they are more active
Term
thyroid follicle
Definition
building block of the organ consists of follicular epithelial cells and colloid and each is surrounded by a basal lamina and is supported by a CT stroma and fenestrated capillaries are located between the follicles where the hormones are secereted
Term
organelles of the follicular epithelial cells
Definition
has a polarization of organelles with basolaterally localized RER a supranuclear golgi complex, small apical secretory granules with the main product being thyroglobulin which is secreted into the lumen (colloid); basolateral plasma membrane of the cells has abundance of receptors for TSH and the Na/I symporter
Term
thyroglobulin
Definition
main component of colloid which is the storage form of thyroid hormones T3/T4 and these are iodinated derivative of tyrosine and part of the primary structure of thyroglobulin; thyroid produces more T4 but T3 is more potent in elicitating biological responses
Term
function of T3 and T4
Definition
stimulate a number of processes including mitochondrial respiration and oxidative phosphorylation are also essential to proper development during embryogenesis
Term
synthesis, storage and secretion of thyroid hormone
Definition
1. formation of thyroglobulin-assembly of aa in RER and addition of sugars in both RER and Golgi, iodination of tyrosyl residues and pacakaging into secretory vesicles; 2. thyrogolbulin is exocytosed from secretory vesciles into follicle where iodide is converted to iodine and iodination of tyrosine residues occurs; 3. endoxytosis of bits of colloid into follicular cell forming colloid droplets; 4. colloid droplets fuse with lysosome and thyroglobulin is hydrolyzed by lysosomal proteases yeilding T3 and T4 and diffuse out of the lysosome and enter fenestrated capillaries and lymphatics
Term
thyroid stimulating hormone regulation
Definition
produced by basophils in the anterior pituitary stimulates both the synthetic steps of thyroblobulin and degradative steps leading to the release of T3 and T4; release is regulated by the TRH and long term stimulation of the thyroid gland leads to an icnrease in the number and size of the follicular epithelial cells
Term
secretion of calcitonin
Definition
parafollicular cells of thyroid gland which the hormones function is decrease the level of Ca in the blood; the cells are larger and pale-staining; often lie in between the basal lamina and the follicular cells or occurs between clusters follicles; difficult to identify without special staining but show morphology characteristic of cells that secrete protein
Term
regulation of calcium levels by calcitonin
Definition
released from the parafollicular cells by exocytosis when the concentration of blood is high and calcitonin lowers blood calcium levels by supressing the release of calcium from bone (resorption from osteoclasts)
Term
general information of parathyroid gland
Definition
typically 3 or 4 which are small and oval structures located in the back of the thyroid arising from pharyngeal pouches and produce PTH which is antagonist to calcitonin and raises blood Ca levels
Term
structure of parathyroid glands
Definition
very cellular and arranged in irregular cords supported by delicated CT or stroma and fenestrated capillaries lie close to the cells; fat cells occur in the gland and increase in number as an individual ages
Term
chief (principal) cells
Definition
most numerous (small, 7-10um in diameter) have small, round, centrally placed and typically dark nucleus there are light and dark chief cells relating to functional state of the cell; responsible for the synthesis and secretion of PTH which is secreted in secretory vesicles
Term
oxyphil cells
Definition
less numerous in the parathyroid glands than the cheif cells; appear during childhood and increase in number with age; larger than chief cells and have abundant acidophilic cytoplasm; filled with lots of mitochondria
Term
parathyroid hormone effect on blood Ca
Definition
brings about a liberation of Ca from bone by stimulating the formation and activity of osteoclasts, stimulating kidney tubules to resorb Ca from the forming urine into blood vessels leading to an increase in Ca in the blood; promoting the synthesis of vit D by the kidney and vit D in turn promotes the absorption of Ca from the digestive tract
Term
PTH effect on phosphate
Definition
inhibits the uptake of phosphate by kidney tubules increasing the amount of phosphate excreted into forming urine;
Term
regulation of PTH release
Definition
stimulated by decline in the amount of Ca in the blood
Term
stimulation of osteoclasts
Definition
PTH binds to osteoblasts which causes an increase in osteoclast by RANK/RANKL and allows the ruffled border to develop from lysosomes to secrete acid and enzymes into the ruffled border these are secreted in Howships lacunae where it causes the resorption of bone increasing the blood Ca level
Term
general information about adrenal glands
Definition
have a cortex and medulla with cortex derived from mesoderm whereas the medulla takes origin from neural crest cells; structure and fucntion are much different
Term
structure of the adrenal cortex
Definition
lies beneath CT capsule and has three zones the cells are arranged in cords and cells rest on a basal lamina and cords wrapped in a delicate ctroma and fenestrated capillaries lie in between the cords of cells and there a no veins in the cortex
Term
cortical cells
Definition
cells of adrenal cortex and synthesize and secrete steroid hormones characterized by SER, mitochondria and lipid droplets
Term
zona glomerosa
Definition
layer lies directly beneath thick CT capsule; arranged in arches resembling balls of cells; secrete aldosterone, mineralcorticoid
Term
zona fasciculata
Definition
widest zone; cells are arranged in long parallel rows that are 1-2 thick many fenestrated capillaries lie between cell columns; contain many lipid droplets which are extracted during tissue preparation; under pituitary control by ACTH and produces glucocorticoids (cortisol) to regulate carbs, protein and fat metabolism
Term
cortisol
Definition
regulates carbohydrate, protein, and fat metabolism and in liver promotes uptake of carbohydrates, fat, and amino acids and stimulates glucose formation; also key in response to stress and suppressing inflammatory and immune responses
Term
zona reticularis
Definition
closest to medulla and cells arranged in irregular cords and have fewer lipid droplets and contatin yellow-brown lipofuscin granules (residual bodies) under ACTH control and produces mainly sex hormones-dehydroepiandrosterone
Term
adrenal medulla
Definition
produces catecholamines and medulla stores its products and releases them in large amounts in response to flight or fight situations
Term
chromaffin cell
Definition
main cell type but have seom autonomic ganglion present as well; derived from neural crest cells are polyhedral and have lightly basophilic cytoplasm and contain numerous membrane-bound secretory vesicles; one type makes epinephrine and another makes norepinephrine arranged in irregular cords
Term
development of chromaffin cells
Definition
no longer have axons or dendrites and each cell is innervated by a preganglionic sympathetic nerve fiber and are modified postganglionic sympathetic nerve cells
Term
function of adrenal medulla
Definition
80% of output is epinephrine causing vasoconstriction, increase HR, and increase in the amount of glucose in the blood, increases O2 consumption and alertness and re-routes blood flow to skeletal muscle, increases rate and depth of breathing, etc.---under control of nervous system
Term
blood supply of adrenal gland
Definition
capsule contains mainy arteries (arterioles) and some enter the cortex where they break up to fenestrated capillaries surrounding all three cortical zones; other branches go directly into the medulla and break up into bed of fenestrated capillaries that are in close contact with chromaffin cells; both capillaires drain into venules located in the medulla with no veins in the medulla and these drain into larger veins that eventually drain adrenal vein
Term
biological effects of thyroid hormone
Definition
acts as an attenuator; 1. regulates BMR, VO2, and body temp by increase ATP usage by increasing Na/K ATPase activity and increasing mitochondrial oxidatitive metabolism; 2. regulates metabolism of carbohydrates, fats, and proteins-increases glycolysis and gluconeogenesis in the liver and sensitizes hepatocytes and adipocytes to epinephrine, increases activity of hormone sensitive lipase, increases glucose uptake and protein synthesis in muscle and lipoprotein metabolism; 3. nervous system and well-being-can result in MR and neurological deficiencies, low levels may cause depression and impaired memory, and hyperthyroidism is associated with irritability, restlessness, and hyperexcitability; 4. bone development and growth-important for GH activity, linear growth and bone mass, hypothyrod children have cretinism features and hyperthyroid children have increased ossification; 5. cardiovascular effects-influences HR and BP by increasing levels of b-adrenergic receptors, relaxes smooth muscle decreasing BP and increasing CO, regulates expression of cardiac genes including PLB, myosin, SERCA2
Term
non-genomic effects of thyroid hormone
Definition
independent of gene expression and include increased glucose and ion transport and actiation of kinase signalling pathways
Term
thyroid hormone structure
Definition
amino acid derivatives of tyrosine that require iodine for biological activity
Term
thyroperoxidase
Definition
enzyme responsible for oxidation of iodide as well as coupling iodine to thyroglobulin occurs in presence of H2O2; incorporation of iodine into tyrosine residues produces mono and di-iodotyrosines
Term
transport of thyroid hormone in the blood
Definition
half life of T4 is 4 days and T3 is 1 day and 99% of hormone is bound and the major carrier protein is thyroxine-binding protein (70%) also carried by transthyretin (TTR) and albumin both (10-15%); there is small fraction that is the biologically active form and is in equilibrium and enters the cells
Term
enzymatic activation and inactivation of thyroid hormones
Definition
majority is released as T4 considered biologically inactive and can be converted to T3 or to inactive rT3 by extrathyroidal deiodination and this is dependent on diodinases containing selenium; these also may be conjugated to glucuronic acid and then exrected in the bile
Term
DIO1
Definition
expressed mainly in adult liver and kidney and localized in plasma membrane with T4 and rT3 preferred substrates and inhibited by PTU and the promoter contains sequences that are responsive to T3 and expression is increased by hyperthyroidism and decreased by hypothyroidism (t1/2=10-30 hrs); may serve as a protective role in normal physiology
Term
DIO2
Definition
expressed in non-neuronal cells in nervous system, skin, brown adipocytes, hearts, skeletal muscle, thyroid gland, and placenta, retained in ER and T4 and rT3 are main substrates and not inhibited by PTU; important role in production of intracellular T3 and contains a cAMP response element for TSH-mediated increases expression in the thyroid gland and has a short half life
Term
DIO3
Definition
expressed in placenta and adult brain and skin localized in plasma membrane and diodinates both T4 and T3 and it transcription is induced by T3 and thought to protect the brain and fetus from excess T3
Term
mechanism of thyroid hormone action
Definition
enters into cells by MCT8 transporter and biologicaly activity mediated by T3 binding to the thyroid hormone nuclear receptor
Term
family of nuclear receptors
Definition
have six domains 1. N-terminus modulator region; 2. xinc fingers for DNA binding; 3. a flexible hinge domain; 4. ligand binding domain that participates in dimerization; 5. variable C-terminal domain; transcription factors whose activity is modulated by ligand binding and receptors bind to DNA sequences (HRE) and regulate gene expression by binding multi-protein regulatory complexes some are nuclear while others are cytoplasmic and translocate to nucleus
Term
thyroid nuclear receptors
Definition
encoded by 2 genes TRa and TRb and expression exhibits tissue specificity; are exclusively nuclear and bind to T3 response elements may bind as monomer, hererodimer, or homodimer; DNA bound TR in absence of T3 represses gene expression and TR-T3 complex induces transcription due to conformational changes that favors binding to either corepressor or coactivator complexes; T3 binding stimulates ubiquination and increases receptor degradation
Term
regulation of thyroid hormone levels
Definition
regulated by negative feedback system where intracellular levels of T3 in thyrotropes and causing respression of TSH and TRH
Term
hyperthyroidism symptoms
Definition
rapid heart rate, warm moist skin, heat intolerance, nervousness, irrtability, insomnia, increased bowel movements, weight loss and fatigue, bulging eyes, and enlarged goiter
Term
causes of hyperthyroidism
Definition
graves disease-antibody induced stimulation of TSH receptor thereby increasing thyroid hormone synthesis and secretion (80% of cases)-hyperactive thyrod, inflammation of tissues surrounding the ye, and localized dermopathy; hot or toxic nodular goiter disease or toxic thyroid adenoma; over-dosing with thyroid replacement hormone; secretion of TSH by pituitary tumor
Term
diagnosis and treatment of hyperthyroidism
Definition
determine serum T3/T4 levels and TSH levels ; with Graves patient-elevated T4/T3, reduced TSH; pituitary adenoma-elevated T4/T3, elevated TSH; toxic nodular disease-thyroid scan, uptake of radioactive I; to treat use radioactive iodine to destroy overactive cells in thyroid; anti-thyroid homrone medication (PTU and metimazole); surgical removal of goiter or entire gland
Term
hypothyroidism symptoms
Definition
fatigue and weakness, weight gain or difficulty losing weight, cold intolerance, dry skin, periorbital edema, brittle hair and alopecia and eybrow thinning, constipation, depression, forgetfulness
Term
hypothyroidsim causes
Definition
iodine deficiency; autoimmune thyroiditis-antibodies to thyroperoxidase, thyroglobulin TSH receptor and/or TSH blocking antibodies; also as a consequence of medical treatment-thyroidectomy, medical treatments-radioactive iodine treatment, over-dosage with anti-thyroid drugs; thyroid hormone resistance-leading to elevated TSH, T4/T3 levels; mutation in gene for protein involved in synthesis of DIO enzymes and T3 levels are low or mutation in MCT8 gene elevation in serum T3 low/normal free T4 and low/normal TSH; or can be secondary due to lack of TSH release from pituitary due to adenomas or tertiary--deficiency in TRH release from hypothalamus
Term
diagnosis and treatment of hypothyroidism
Definition
1. diagnosis-autoimmune thyroiditis elevated level of antibodies against various thyroid gland proteins, elevated levels of TSH and presence of goiter; medical treatment-case history and elevated levels of TSH; iodine deficiency-analysis of diet, elevated TSH, and goiter; thyroid hormone resistance-a defect or deficiency in TR or pathways, goiter, T4/T3 elevated, TSH normal
Term
euthyroid sick syndrome
Definition
low serum levels of thyroid hormone in euthyroid patients with nonthyroidal illnesses, most common is low T3 and elevated rT3; found in patients with acute and chronic illness including anorexia, CVD, renal failure, sepsis and burns; TSH levels low to normal
Term
synthesis of adrenal steroid hormones
Definition
conversion of cholesterol to common precursor pregnenelone is first step and StAR controls the transfer of cholesterol into the mitochondria where the P450scc cleaves cholesterol to 21-C prenenolone; StAR regulated by cAMP and PKC as well as extracellular K+
Term
glucocorticoid/mineralcorticoid acitivity
Definition
to posess this activity must consit of 21 carbons a CO-CH2OH side chain on C17 unsaturated bond between C4 and C5 and a ketone group at C3 and glucocorticoid activity is greatly increased by OH at C11 whereas C21 and -O at C18 enhance mineralcorticoid activity
Term
zona glomerulus enzymes
Definition
lacks CYP-17 and instead cells express CYP 11B2 that oxidizes both C11 and C18 and the C18 is oxidized to aldehyde to confer specificity
Term
zona reticularis development
Definition
matures around the onset of puberty increasing in both size and androgen synthesis and decline in production begins in the mid-20s and continues over the remaining life span
Term
regulation of adrenal steroid hormone release
Definition
steroid hormones not stored but diffuse into circulation as they are produced and circulating levels of cortisol follow a diurnal rhythm with a 10-fold difference between the highest (8AM) and lowest levels (12AM) closely resembles ACTH releases
Term
steroid bind proteins
Definition
cortisol binds with high affinity to corticosteroid-binding globulin (CBG) or transcortin while a smaller fraction is bound to albumin and the free cortisol is biologically acitve form and is about 10% of plasma level (half life is about 100 min); aldosterone does not have as great of affinity for CBG and much more free aldosterone and that bound to albumin and is cleared much faster from the blood
Term
regulation of cortisol synthesis
Definition
stresses result in release of corticotropin releasing hormone from the paraventricular nucleus released in hypothalamo-hypophyseal portal blood and causes a cAMP dependent release of ACTH product of POMC polypeptide and ACTH is released into the plasma and remain unbound and interacts with GPCR on all three zones of the cortex and increases the conversion of cholesterol to pregnenolone, cholesterol transport into mitochondria and incresaed blood flow stimulating cortisol synthesis and secretion; cortisol is negative regulator of CRH and ACTH synthesis and release
Term
synthesis of ACTH
Definition
processing of POMC precursor is tissue specific; excess ACTH resulting from either adrenal insufficiency or a tumor and often result in hyperpigmentation the increased levels of ACTH and processed a-MSH stimulate melanocytes
Term
steroid-binding nuclear receptors
Definition
GR and MR receptors are cytoplasmic in absence of bound ligand Hsp bind to cytoplasmic GR and MR monomers; ligand binding alters GR and MR conformation releasing Hsp and unmasking both NLS and dimerization domain and steroid bound homodimers translocate into nucleus and bind a consensus DNA HRE target gene expression can be either induced or repressed; GR ubiquitously expressed whereas MR is expressed in epithelial cells in kidney, sweat glands and GI tract, vascular endothelial cells, and cardiac and neural cells
Term
biological effect of glucocorticoids
Definition
1.effect on fuel metabolism-increase blood glucose levels-decreases uptake by GLUT4(decreases insulin sensitivity),increases lipolysis, increases proteolysis while decreasing protein synthesis and increases hepatic gluconeogenesis; 2. increases storage of glucose and glycogen synthesis and deposition is stimulated; important during the developmental maturation of organ, alveoli maturation and surfactant production, normal blood pressure and CO, mental well-being, induces lipocotin1 that inhibits phospholipaseA2 and inhibiting prostaglandin and leukotriene synthesis from arachidonic acid and blocking inflammation; inhibits inflammation process by interfering with NF-kB and elevated levels of glucocorticoids will lead to osteoporosis by decreased Ca absorption in GI, decreased Ca reabsorption by the kidney, decreased osteoblast function and increased osteoclast number and activity
Term
cortisol and metabolic syndrome
Definition
enzyme responsible for generating cortisol from biologically inactive cortisone is 11-Bhydroxysteroid dehydrogenase 1-localized enzyme indevelopment of metabolic syndrome and obesity; overexpression increases visceral fat and a metabolic like phenotype in animals have elevated levels in fat cells but maintain normal serum levels; whereas knockout mutations show they are resistant to effects of high fat diet on weight gain and glucose tolearance is maintained and shows HDL cholesterol elevation and reduced TGs
Term
adrenal androgens
Definition
two androgens are produced by zona reticularis, DHEA and androstenedione neither which bind to androgen receptor and these are precursors to peripheral conversion to more potent hormones and sulfated form of DHEA (DHEAS) is produced in highest concentration
Term
synthesis of DHEA
Definition
occurs in zona reticularis 19C is derived from 17ahydroxypregnenolone by cleavage between C17 and C20 and the enzyme CYP17 is responsible for both C17-OH of pregnenolone and cleavage; androstenedione can be synthesized from DHEA by oxidation of C3 or by cYP17 cleavage of 17a hydroxyprogesterone
Term
function of adrenal androgens
Definition
responsible for inducing pubic and axillary hair growth during adrenarch and increased synthesis of DHEA corresponds to an increase in the size of zona reticularis during puberty; in women undergo peripheral intracrinology and main source of estrogen for post-menopausal women
Term
synthesis of aldosterone
Definition
starts from pregnenolone lack CYP and instead the mitochondria contain CYP11B2 with 18ahydroxylase activity
Term
biological activity of aldosterone
Definition
enters cell binds MR therby altering receptor conformation releasing Hsp90, this receptor binds cortisol and aldosterone with similar high affinity
Term
11BHSD2
Definition
in aldosterone responsive tissues inactivates cortisol and acts as a prereceptor regulator; in these cells the MR bound receptor acts as TF and induces Sgk1, epithelial Na channel and Na/K ATPase
Term
binding of angiotensin II
Definition
binds to AT1 receptors while ACTH has a permissive effect and results in rise in Ca and in turn increases the levels of StAR and K affects the membrane potential of cells and opens Ca channels and increasing intracellular Ca
Term
Addisons disease
Definition
adrenal insufficiency from infiltrative causes or an autoimmune reaction and secondary causes include lack of ACTH or lack of CRH also may result from acute cessation of long-term glucocorticoid usage; includes chronic fatigue, weight loss, and muscle weakness, hypotension, nausea, vomiting, bronze appearance in skin and mucous membranes, salt craving, impotence or decrease in libido; low levels of cortisol and aldosterone and failure to rise after injection with ACTH detection of autoantibodies against 21-hydroxylase
Term
Cushings syndrome
Definition
hypercortisolemia is ACTH dependent of ACTH independent and ACTH dependent includes ACTH secreting pituitary adenoma or non-pituitary tumor and ACTH independent include adrenal adenoma or prolonged parmacological use of glucocorticoids; weight gain with central obesity, moon-face, hypertension, impaired glucose tolerance, diabetes, hypogonadism, menstraul irregularity, libido loss, osteoporosis, muscle weakness, and loss of muscle mass, hyperpigmentation, hirsutism in women, bruising and purplish striae on abdomen; 24 hr urinary free cortisol determination and low dose dexmethasone suppression test overnight and serum cortisol measured in the morning and in normal individuals this suppresses both ACTH and cortisol
Term
Conns syndrome
Definition
primary hyperaldosteronism, increased secretion of aldosterone independent of renin levels; systemic hypertension, headaches, hypokalemai and mild hypernatremia, muscle weakness; diagnosis hypernatremia and hypokalemia plasma aldosterone will be elevated and renin levels will be decreased
Term
secondary hyperaldosteronism
Definition
activation of circulating RAS and further characterized by presence or absence of hypertension; systemic hypertension, headaches, hypokalemia and hypernatremia, muscle weakness; urinary 24 hr aldosterone levels, elevated AngII and renin levels
Term
congenital adrenal hyperplasia
Definition
enzyme deficiency blocking normal steroid hormone biosynthetic pathways and resultant buildup of intermediates and shunting of substrates to androgen synthesis cytochrome P450c21hydroxylase reducing both cortisol and aldosterone; virilization of female external genitalia; adrenal insufficiency or precocious puberty and short adult stature
Term
lipoid congenital adrenal hyperplasia
Definition
caused by mutation is StAR gene lead to a blockade in steroidgenesis by adrenal gland and the gonad results in buildup of intracellular cholesterol include female external genitalia, hyponatremia, hyperkalemia and dehydration, increased pigmentation, elevated ACTH and renin and decreased levels of cortisol and death can result
Term
definition of obesity
Definition
excess body fat in relation to lean body mass; underweight is less than 18.5, normal is 18.5-24.9, overweight is 25-29.9 and obese is greater than 30; waist circumference is also a high risk factor with men greater than 40 in and women greater than 35 inches (refers to visceral abdominal fat)
Term
etiology of obesity
Definition
arises from consuming more energy than one is expending; hunter-gathers selected for thrifty genes that allowed for weight gain and storage and decrease in weight loss; during times of famine there is increase in efficiency it helps limit weight loss and during times of feast maximum energy is stored and in our society is feast-feast situation with decreased energy expenditure
Term
hostile environment leading to obesity
Definition
includes high calorically dense foods, senedtary activities, work savers, television, stress, lack of sleep, unsafe neighborhoods, decreased physical activity
Term
gene and environement interaction
Definition
SNPS in genes showed correlation with obesity in different cohorts; other studies showed that increase in weight gain in one person associated with weight gain in his or her friends, siblings, spouse, or neighbors
Term
putative contributions to increased obesity
Definition
sleep debt-hrs of sleep inversely related to BMI; endocrine disruptors-environmental stable, industrial products (PBDE); reduced variability in ambient temperature (is AC); assortive mating
Term
health consequences of obesity
Definition
HTN, type 2 diabetes, CAD, gallbladder disease, dyslipidemia, stroke, osteoartritis, sleep apnea, cancers
Term
mechanisms of obesity for mortality and mobidity
Definition
stimulates inflammation response and increased PAI-1, IL-6, TNFa, angiotensinogen and increased vascular inflammation cause endothelial dysfunction and insulin resistance causing atherosclerosis and CVD; VAT is most strongly related to metabolic risk factors
Term
long acting adiposity hormones
Definition
act more slowly to maintain the stability of fat stores, act in several sites within the CNS and converge in the hypothalamus
Term
central-hypothalamic main orexigenic peptides
Definition
make you eat more include neuropeptide Y and Agouti-related protein
Term
central-hypothalamic main anorexigenic peptides
Definition
make one stop eating include melanocortins
Term
peripheral peptides
Definition
orexigenic includes ghrelin and anorexigenic includes peptide YY, CCK, leptin and insulin
Term
neuropeptide Y
Definition
one of the most abundent and potent peptide in the hypothalamus and is central orexigenic peptide and ARC is major site of expression and chronic administration results in hyperphagia, decreased thermogenesis, and obesity; a decrease in leptin and insulin causes an increase in synthesis and secretion
Term
AGRP
Definition
central orexigenic peptide and expressed in the ARC and neurons producing AGRP co-secrete NPY and these inhibit the melanocortin receptors; central and chronic administration shown to cause hyperphagia and lead to obesity and leptin inhibits release of AGRP
Term
ghrelin
Definition
peripheral orexigenic peptide produced in endocrine cells of gastric mucosa also has been found in prox small intestine, pituitary, hypothalamus, pancreas, lung, placenta, ovary, testis, kidney; these levels increase before a meal and decreased after feeding and stimulates production of NPY and AGRP in ARC and antagonizes leptin
Term
melanocortins
Definition
(aMSH) is central anorectic peptide derived from POMC act as agonists for melanocortin-4 receptor which is involved in appetite and energy homeostasis; POMC stimulated by leptin; inhibits feeding and reduces body weight and has been shown to inhibit AGRP; mutations in MC4 receptor result in obesity
Term
peptide YY
Definition
peripheral anorectic peptide produced in intestinal L cells in distal segments of GI tract; released following food intake causes delayed gastric emptying and delayed gastric secretions and pancreatic; act on receptors in the ARC and inhibitsNPY/AGRP neurons and possibly stimulates POMC neurons
Term
CCK
Definition
peripheral anorectic peptide produced in GI tract and in the brain; released in response to nutrients (fat and protein) reduces meal size only if administered 15-30 min before a meal
Term
Leptin
Definition
peripheral anorectic peptide synthesized in white adipose tissue and reflects total body adipose tissue mass during periods of weight maintainence; from ob gene and mutations decreases circulating leptin and hyperphagic obese phenotype; binding to receptor in ARC inhibits NPY,AGRP and stimulates anorectic peptides (aMSH); under conditions of food restriction leptin levels in repressed and in obese individuals it is increased
Term
treatment of obesity
Definition
dietary therapy, physical activity, behavioral therapy, combined therapy, pharmacotherapy, weight loss surgery
Term
health behavior theory
Definition
health belief model-perceptions of individual, intervention, and self efficacy; transtheoretical model-stages of change (precontemplation, contemplation, preparation, action, and maintainence) support progression to higher stages and tailor intervention and education to stage and reinforce self-efficacy; social cognitive theory-guide and modify perceptions and beliefs, structure environment to support behavior change, role-modeling, positive reinforcement of behavior change, self-efficacy
Term
pharmacotherapy for weight loss
Definition
orlistat 2.9kg weight loss reduced incidence of DM and increased rates of GI side effects; sibutarine-centrally acting monoamine reuptake inhibitor average 4.2 kg weight loss loweredd TG and raised HDL-C raised BP and HR
Term
rimonanbant
Definition
CB1 receptor antagonist/inverse agaonist; putative activity-mesolimbic and central melanocortin systems, potentiation of brainstem CCK and vagal satiety signals but has concerns for increasing depression
Term
long term maintainance of weight loss
Definition
backwards, flattened J; include behavioral aspects (burnout, lack of positive feedback, different theoretical structures needed); hostile environment; disconnect between patient expectations regarding weight and positive health benefits of weight loss
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