secrete molecules into the blood,  are ductless

carry hormones to target cells that have specific receptor proteins for that hormone

Target cells respond in a specific way they affect the metabolism of the target organs and help regulat total body metabolism, growth and reporduction.

neorohormones specilized neurons that secrete chemical into the blood rather than synaptic clift  the chemical secreted is a neurohormone

Amines:  hormones derived from tyrosine and tryptophan

and these are norepinephrine, epinephrine, T4

Polypetpides and proteins  polypeptides are chains of less than 100 amino acids long =  ADH

Protein hormones polypeptide chains with more than 100 amino acids = growth hormone

Lipids derived from cholesterol and they are testosterone, estradiol, cortisol, progesterone

Glycoproteins:  long polypeptides (>100) bound to one or more carbohydrates groups = FSH and LH

Polar hormones that are water soluable

Nonpolar (lipophilic)  love fat  are not soluble in water.

can gaine entry into target cells

they are steroid hormones and T4

Pineal gland secetes melatonin and has properties of both water soluble and lipophilic hormones

Neural and endocrine regulation

chemical events produce by diffusion of ions through neuron plasma membrane

how to send message down neuron to muscle

target cell must ahve receptor

necessary for

a neurotransmitter or hormone

to function in

physiological regulation

target cell must have specific receptor proteins

combination of regulatory molecule with its receptor

proteins must cause a specific sequence of changes

MUST be a way to quickly turn off the action of a regulator

synergistic  = 2 hormones work together to produce a result by

(a) additive where each hormone separately produces respons, together at same concentrations stimulate even greater effect like norepinepherine and epinephrine

(b) Complementary = each hormone stimulates different step in the process like FSH and testosterone.

(c) Permissive effects where the hormone enhances the responsiveness of a target organ to secnd hormone.  Increases the activity of a second hormone.  like prior exposure of uterus to estrogen induces formation of receptor for progesterone.

(d) antagonistic effect where the action of one hormone antagonizes the effects of another such as insulin and glucagon

(e) desensitization (downregulation)  prolonged exposure to same hormone produces less response can be from decrease in number of receptor ontarget cells like insulin in adipose cells in type II DM.   pulsatile secretion may prevent downregulation.  Spurts work best.

Hormones of the same chemical class have similar ways or action

similarities  include

(a) location of cellular receptor proteins depend on the chemical nature of the hormone

(b) Events that occur in the target cells

target cell must have specific treceptors for that hormone

specificity

Hormones exhibit affinity (bind to receptors with high bond strength)

Saturation (low capacity of receptors)

type 2 diabetes ..saturation receptor

Lipophilic steroid and thyroid hormones are attached to plasma carrier proteins in the blood.

Hormones dissociate from carrier proteins to pass through the lipid component of the target plasma membrane

Receptors for the lipophilic hormones are know as

nuclear hormone receptors

steroid are fat soluable.  travel in blood attached to protein carrier

At arrival to target sells they separate from their carriers and pass through the plasma membrane. 
Some steroid hormones bnd to specific receptor proteins in the cytoplasm and then move as a hormone-receptor complex into the nucleus.

Other steroids travel directly into the nucleus before encuntering their receptor proteins.  The hormone receptor protein, activated by binding to the hormone, is now able to bind to a specific region of DNA.  These DNA regions are know as the hormone response elements (HRE). 

The binding of the hormone response complx has a direct effect on the level of transcription at that site.  Messenger RNA is produced, which then codes for the synthesis of specific proteins.

homodimerization

aldosterone is a lipid-soluble hormone that diffuses through the membrane.

Inside the cell it binds with an aldosterone receptor protein in the cytoplasm.  the aldosterone-receptor complex moves into the nucleus and binds to DNA.  The binding stimulates the synthesis of mRNA which codes for specific proteins (translation).  These proteins produce the response of the cell to aldosterone.

I think it uses heterodimerization

Steroid receptors are located in the cytoplasm and in the nucleus.

They function in the cell to activate genetic transcription

Each nuclear hormone receptor has 2 regions

1. a ligand (hormone)-binding domain

2. DNA - binding  domain                   

the receptor must be activated by binding to hormone before binding to specific regions of DNA called HRE (hormone response element)  located adjacent to gene that will be transcribed.

T4 passes into cytoplasm and is converted to T3

receptor proteins located in nucleus--

T3 binds to ligand-binding domain

The other half-site is a vitamin A derivative (9-cis-retinoic) acid   (heterodimerization)

Two parteners can bind to the DNA to activate HRE..so simutaneous transcription of genes

Again:

Thyroxine is a fat soluble hormone that is brought to the target cell via a protein carrier (throid binding globulin - TBG).

It is lipophilic and so can easily pass through the cell membrane.

T3 enters the nucleus and binds to nuclear receptor proteins. 

The hormone-receptor complex binds to the hormone response elements HRE on DNA.  The binding of the hormone-receptor complex influence the level of transcription at the site where it binds.  mRNA is produced and codes for specific proteins.

Thyroid uses a heterodimerization to RNA

Hormones that cannot pass through the membrane use 2nd messengers.

Catecholamine, polypeptide, and glycoprotein

hormones beind to receptor proteins on the target membrane

Actions are mediated by 2nd messengers (signall-transduction mechanisms).

Extracellular hormones are transducted into intracellular 2nd messengers

Cyclic AMP (cAMP)

Phospholipase  C - Ca++

Tyrosine Kinase

The second messenger

Adenylate Cyclase-Cyclic AMP  (cAMP)

Polypeptide or glycoprotein hormone

binds to receptor protein causing dissociation of a subunit of G Protein

G protein subunit binds to and activates adenylate cyclase

ATP   >  cAMP  +  P

cAMP attaches to inhibitory subunits of protein kinase

Inhibitory subunit dissociates and activates protein kinase

Phosphorylates enzymes in the cell to produce hormone's effects.

Modulates activity of enzymes present in the cell

Alters metabolism of the cell

cAMP inactivated by phosphodiesterase

Hydorlyzes cAMP to inactive fragments.

The second messenger

Phospholipase - C - Ca++

Binding of epinephrine to a-adrenergic receptor in membrane    activates a   G protein intermediate, phospholipase C

Phospholipase C splits phospholi[id into IP3 and DAG

and both derivatives serve as 2nd messengers

IP3 diffuses through the cytoplasm to endoplasmic reticulum (ER)

Binding I IP3 to receptor protein in ER causes Ca++ channels to open  (needed for muscle contraction)

Ca++ binds to calmodulin

Calmodulin activates specific protein kinase enzymes

aslters the metabolism of the cell producing the hormone"s effects

The second messenger

Tyrosine Kinase

and insulin

Insulin receptor consists of 2 units that dimrize when they bind with insulin

-----Insuline binds to ligand-binding site on membrane, activating enszymatic site in the cytoplasm

Autophosphorylation occurs, increasing tyrosine kinase activity

Activates signaling molecules

-----stimulate glycogen, fat and protein synthesis

-----stimulate insertion of GLUT - 4 carrier proteins

in the vesicle membrane  this causes the intracellular vesicles to translocate and fuse with the plasma membrane so it becomes part of the membrane

GLUT 4 permits the facillitated diffusion of glucose from the extracellular fluid into the cell

The beta chain spans the membrane and the alpha unit has the insulin binding site

called the master gland but is controlled by the hypothalmus

It is a reddish color

Will not do anything unless hypothalmus tells it to

pituitary gland = adenohypophysis

TSH   and   ATCH

derived from a pouch of epithelial tissure that migrates upward from the mouth

Consists of 2 parts 

pars distalis:  anterior pituitary

pars tuberalis:  thin extension in contact with the infundibulum

secretes tropic hormones

Does not make anything

It is white...like from nerve fiber

Stores and releases 2 hormones that are produce in the hypothalamus:

Antidiuretic hormone (ADH)  that promotes the retention of H2O by the kidney..less water is excreted in the urine

the only receptor for ADH is in the kidney

Oxytocin:  Stimulates contracions of the uterus during parturition

Stimulates contractions of mammary gland alveoli = milk - ejection reflex = feed back mechanism

Hormonal control rather than neural

hypothalamus neurons synthesize   releasing and inhibiting hormones

Hormones are transported to axon end of median eminence

Hormones secreted into the

hypothalamo-hypophyseal portal system

regulate the secretions of anterior pituituary

hormones from the hypothalmus

will have and   RH at the end

stands for releasing hormone

GnRH has to do with reproduction

Corticotoropin-releasing hormone CHR  stimulates secretion of adrenocortocotropic hormone (ATCH)

Gonadotropin-releasing hormone GnRH  stimulates secretion of FHS and Lh

Prolactin-inhibiting hormon PIH  inhibits prolactin secretion

Somatostatin Inhibits secretion of growth hormone

thyrotropin=releasing hormon TRH  stimujlates secretion of TSH

Growth hormoone-releasing hormone  GHRH

stimulates growth hormone secretion

anterior pituitary and hypothalmic secretion are controlled by the target organs they regulate

secretions are controlled by negative feedback inhibition by target gland hormones

negative feedback at 2 levels

1. the target gland hormone can act on the hypothalamus and inhibit secretion of releasing hormones

2. the target gland hormone can act on the anterior pituitary and inhibit response to the releasing hormone

there is a short feedback that sends blood fromthe anterior pituitary to the hypothalamus..hormone released by anterior pituitary inhibits secretion of RH

Positive feedback:

During mense cycle, estrogen stimulates LH surge to ovulate  thus you can test when fertile

hypothalamus > TRH

anterior pituitary > TSH

thyroid that produces T4

and TSH causes growth of thyroid

follow the hypothalmus-pituitary-gonad axis

(control system)

hypothalmus  GnRH

anterior pituitary  gonadotropins (FSH and LH)

gonads  sex steroid hormones estrogens and androgens

Higher brain function and pituary secretion

Axis

Axis -- relationship between anterior pituitary and a particular target gland

such as pituitary-gonad axix

in this the negative feed back goes to the hypothalmus and skips the pituitary

The hypothalmus receives input from higher brain centers so psychological stress affect:

circadian rhythms

menstrual cycle

zona glomerulosa

-----mineralcorticoids (aldosterone) that stimulate the kidneys to reabsorb Na+ and secrete K+

zona fasciculata

-----glucocorticoids (cortisol) that inhibits glucose utilization and stimulate gluconeogenesis

stress influences

zona reticularis (DHEA) dehydroepiandrosterone (androgens):  sex steroids =supplemental sex steroids

Paired organs that cap the kidneys..look like fat

outer cortex (controlled by anterior pituitary)

and inner medulla = derived from same tissue that produces sympathetic ganglia.  It synthesizes and secretes Catecholamines, mainly epinephrine and some norepinephrine

Three zones of the adrenal cortex

and a little about it

zona glomerulosa = aldosterone

Zona fasciculate = cortison

Zona reticularis  (deepest) = DHEA

it does not receive nural innervation

must be stimulated hormonally by ATCH from the anterior pituitary

releasing hormone is CRH

innervated by prganglionic sympatheitc axons

increases respiratory rate

Increases HR and cardiac output

vasoconstrictin to blood vessels of the gut thus incresing venous return

stimulates glycogenolysis

stimulates lipolysis

epinephrine and norepinephrine

fight or flight

part of the sympathetic nervous system

nerve origin

Non-specific response to stress produces

general adaption syndrome (GAS)

Alarm phase:  adrenal glands activated

Stage of resistance: stage of readjustment

Stage of exhaustion: sickness and/or death if readjustment is not complete

the thyroid gland is located just below the larynx and just above the thoracic notch

Thyroid is the largest of the  pure endocrine glands

follicular cells secrete thyroxine

parafollicular cells secrete calcitonin

Iodide (I-)  actively transported into the folicle and secreted into the coloid

T3 and T4 are producedd

TSH stimulates  pinocytosis into the follicular cell

Attached to TBG (thyroid binding globulin) and released into the blood

Stimulates protein synthesis

promotes maturation of nervous system

stimulates rate of cellular respiration by:

-----production of uncoupling proteins

-----increase active transport by Na+/K+ pumps

-----Lower cellular ATP by using it up

increases metabolic heat

increases metabolic rate

-----stimulates increased consumption of glucose, fatty acids and other molecules

Iodine-deficiency (endemic) goiter

goiter is the abnormal growth of the thyroid gland in the absence of sufficient iodine...cannot produce adequate amounts of T4 and T3

this causes negative feedback inhibition

Stimulates more TSH which causes the abnormal growth

Adult myxedema = edema all over.  accumulationof mucoproteins and fluid in subcutaneous tissue

symptoms of low thyroid

decreased metabolic rate

weight gain

decreased ability to adapt to cold

lethargy

Graves disease:  exerts TSH-like effects on thyroid -------not affected by negative feedback...will have

low TSH levels

Cretinism = hypothyroid from end of 1st trimester to 6 months postnatally    severe mental retardation

it is NOT involved with the pituitary

enbedded in the lateral lobes of the thyroid gland

parathyroid hormone ( PTH);

this is the only hormone secreted by the parathyroid gland

PTH is the single most important hormoone in the control of blood Ca++

Stimulated by decreased blood Ca++

Promotes rise in blood Ca++ by actin on bones, kidnesy and intestines

muscles cannot work with out Ca++ (remember the downed cow)

twitchy unsteady on feet   tremor hypocalcemia

Most of the thyroid is exocrine = pancreatic juice

and then there is the Islets of Langerhans

that have alpha cells and beta cells

Alpha cells secrete glucagon for low BS

lipophobic..never enter the cell

 decrease in blood glucose causes release of glucagon

alpha cells stimulates glycogenolysis and lipolysis

Alpha cells stimulate conversin of fatty acids to ketones

elevates blood sugar

beta cells secrete insulin  

lipophobic  never enters the cell

increase in blood glucose causes release of insulin

promotes entry of glucose into the cells

converts glucose to glycogen and fat

aids entry of amino acids into cells

Secretes melatonin

production stimulated by hypothalamus

primary center for circadian rhythms

light / dark changes are required to syncronize

Melatonin secretion increases with darkness and peaks in middle of night

may inhibit GnRH 

may functin in the onset of puberty

thymus gland is in the chest just above the heart

It is the site of T cells (thymus-dependent cells), which are lymphocytes...involved in cell-mediated immunity

Secretes hormones believed to stimulate T cells after leae thymus...thymus is large in newborns and kids

Thymus regresses after puberty and becomes infiltrated with strands of fibrous tissue

Gonads =  testes  and  ovaries

secrete sex hormones  estradiol /  estrone > menopause

progesterone

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Placenta secretes large amounts of estrogen, progesterone,   placenta hCG, hCS

Autocrine = produced and act within the same tissue

of an organ

all autocrine regulators control gene expression in target cells

examples:  Cytokins (lymphokines) that regulate different cell (interleukins) of the immune system

growth factors:  promote growth and cell division in any organ

Neutrophins: guide regenerating peripheral neurons

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Paracrine = produced withone one tissue and regulate a different tissue of the same organ

the most diverse group of autocrine regulators

produced in almost every organ

wide variety of functions

different prostaglandins may exert antagonistic effects in some cells

--------

Inhibitors of prostaglandin synthesis

NSAID  

aspirin, etc   inhibit COX-1

celecoxib and rofecoxib  inhibit  COX-2