1. Amino acid based hormones.

    *Amines, Thyroxine, Peptides, and Proteins.

2. Steroids

    *Snythesized from cholesterol.

    *Gonadal and Adrenocortical hormones.

They can:

1. Alter plasma membrane permeability of membrane potential by opening or closing ion channels

2. Stimulate synthesis of proteins or regulatory molecules

3. Activate or deactivate enzyme systems

4. Induce secretory activity

5. Stimulate mitosis

• Cannot enter the target cells

• Act on plasma membrane receptors

• Coupled by G proteins to intracellular second messengers that mediate the target cell’s response

1. Hormone (first messenger) binds to receptor

2. Receptor activates G protein

3. G protein activates adenylate cyclase

4. Adenylate cyclase converts ATP to cAMP (second messenger)

5. cAMP activates protein kinases 

6. Activated kinases phosphorylate various proteins, activating some and inactivating others 

7. cAMP is rapidly degraded by the enzyme phosphodiesterase 8.Intracellular enzymatic cascades have a huge amplification effect

Steroid hormones and thyroid hormone

1. Diffuse into their target cells and bind with intracellular receptors

2. Receptor-hormone complex enters the nucleus

3. Receptor-hormone complex binds to a specific region of DNA

4. This prompts DNA transcription to produce mRNA

5. The mRNA directs protein synthesis

• Target cells must have specific receptors to which the hormone binds

• ACTH receptors are only found on certain cells of the adrenal cortex

• Thyroxin receptors are found on nearly all cells of the body

1. Blood levels of the hormone

2. Relative number of receptors on or in the target cell

3. Affinity of binding between receptor and hormone

Yes.

• Up-regulation—target cells form more receptors in response to the hormone

• Down-regulation—target cells lose receptors in response to the hormone

Both.

• Steroids and thyroid hormone are attached to plasma proteins

• All others circulate without carriers

• Degrading enzymes

• Kidneys

• Liver

• Half-life—the time required for a hormone’s blood level to decrease by half

• Rate of release

• Speed of inactivation and removal from the body

1. Permissiveness: one hormone cannot exert its effects without another hormone being present

2. Synergism: more than one hormone produces the same effects on a target cell

3. Antagonism: one or more hormones opposes the action of another hormone

• By negative feedback systems

• Vary only within a narrow desirable range

1. Humoral stimuli

2. Neural stimuli

3. Hormonal stimuli

1. Changing blood levels of ions and nutrients directly stimulates secretion of hormones

• Example: Ca2+ in the blood

 Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone).  PTH causes Ca2+ concentrations to rise and the stimulus is removed

• Nerve fibers stimulate hormone release

• Sympathetic nervous system fibers stimulate the adrenal medulla to secrete catecholamines

• Hormones stimulate other endocrine organs to release their hormones

• Hypothalamic hormones stimulate the release of most anterior pituitary hormones • Anterior pituitary hormones stimulate targets to secrete still more hormones

• Hypothalamic-pituitary-target endocrine organ feedback loop: hormones from the final target organs inhibit the release of the anterior pituitary hormones

 The nervous system modifies the stimulation of endocrine glands and their negative feedback mechanisms

• Example: under severe stress, the hypothalamus and the sympathetic nervous system are activated.  As a result, body glucose levels rise

1. Posterior pituitary (lobe):

• Pituicytes (glial-like supporting cells) and nerve fibers

2. Anterior pituitary (lobe) (adenohypophysis)

• Glandular tissue

• A downgrowth of hypothalamic neural tissue

• Neural connection to the hypothalamus (hypothalamic-hypophyseal tract)

• Nuclei of the hypothalamus synthesize the neurohormones oxytocin and antidiuretic hormone (ADH)

• Neurohormones are transported to the posterior pituitary

• Originates as an out-pocketing of the oral mucosa

• Hypophyseal portal system

• Primary capillary plexus

• Hypophyseal portal veins

• Secondary capillary plexus

• Carries releasing and inhibiting hormones to the anterior pituitary to regulate hormone secretion

• Growth hormone (GH)

• Thyroid-stimulating hormone (TSH) or thyrotropin

• Adrenocorticotropic hormone (ACTH)

• Follicle-stimulating hormone (FSH)

• Luteinizing hormone (LH)

• Prolactin (PRL)

• All are proteins

• All except GH activate cyclic AMP second-messenger systems at their targets

• TSH, ACTH, FSH, and LH are all tropic hormones (regulate the secretory action of other endocrine glands)

• Produced by somatotrophs

• Stimulates most cells, but targets bone and skeletal muscle

• Promotes protein synthesis and encourages use of fats for fuel

• Most effects are mediated indirectly by insulin-like growth factors (IGFs)

• Stimulates liver, skeletal muscle, bone, and cartilage to produce insulin-like growth factors

• Mobilizes fats, elevates blood glucose by decreasing glucose uptake and encouraging glycogen breakdown (anti-insulin effect of GH)

GH release is regulated by:

1.Growth hormone–releasing hormone (GHRH)

2.Growth hormone–inhibiting hormone (GHIH) (somatostatin)

• Hypersecretion

1.In children results in Gigantism 

2.In adults results in Acromegaly

• Hyposecretion

1.In children results in Pituitary Dwarfism

• Produced by thyrotrophs of the anterior pituitary

• Stimulates the normal development and secretory activity of the thyroid

• Regulation of TSH release

• Stimulated by thyrotropin-releasing hormone (TRH)

• Inhibited by rising blood levels of thyroid hormones that act on the pituitary and hypothalamus

A. Secreted by corticotrophs of the anterior pituitary

  • Stimulates the adrenal cortex to release corticosteroids

B. Regulation of ACTH release

  1. Triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythm

  2. Internal and external factors such as fever, hypoglycemia, and stressors can alter the release of CRH

• Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

• Secreted by gonadotrophs of the anterior pituitary

• FSH stimulates gamete (egg or sperm) production

• LH promotes production of gonadal hormones

• Absent from the blood in prepubertal boys and girls

*** Regulation of gonadotropin release***

1.Triggered by the gonadotropin-releasing hormone (GnRH) during and after puberty

2.Suppressed by gonadal hormones (negative feedback)

• Secreted by lactotrophs of the anterior pituitary

• Stimulates milk production

• Regulation of PRL release

• Primarily controlled by prolactin-inhibiting hormone (PIH) (dopamine)

• Blood levels rise toward the end of pregnancy

• Suckling stimulates PRH release and promotes continued milk production

• Contains axons of hypothalamic neurons

• Stores antidiuretic hormone (ADH) and oxytocin

• ADH and oxytocin are released in response to nerve impulses

• Both use PIP-calcium second-messenger mechanism at their targets

• Stimulates uterine contractions during childbirth by mobilizing Ca2+ through a PIP2-Ca2+ second-messenger system

• Also triggers milk ejection (“letdown” reflex) in women producing milk

• Plays a role in sexual arousal and orgasm in males and females

A. Hypothalamic osmoreceptors respond to changes in the solute concentration of the blood

B. If solute concentration is high 

   1. Osmoreceptors depolarize and transmit impulses to hypothalamic neurons

   2.ADH is synthesized and released, inhibiting urine formation

C. If solute concentration is low

   1.ADH is not released, allowing water loss

D. Alcohol inhibits ADH release and causes copious urine output

1. ADH deficiency—diabetes insipidus; huge output of urine and intense thirst

2.ADH hypersecretion (after neurosurgery, trauma, or secreted by cancer cells)—syndrome of inappropriate ADH secretion (SIADH)

• Consists of two lateral lobes connected by a median mass called the isthmus

• Composed of follicles that produce the glycoprotein thyroglobulin

 • Colloid (thyroglobulin + iodine) fills the lumen of the follicles and is the precursor of thyroid hormone

• Parafollicular cells produce the hormone calcitonin

Actually two related compounds:

 • T4 (thyroxine) has 2 tyrosine molecules + 4 bound iodine atoms

• T3 (triiodothyronine) has 2 tyrosines + 3 bound iodine atoms

• Is a Major metabolic hormone

• Increases metabolic rate and heat production (calorigenic effect)

• Plays a role in:

  1. Maintenance of blood pressure

  2.Regulation of tissue growth

  3.Development of skeletal and nervous systems

  4.Reproductive capabilities

• Thyroglobulin is synthesized and discharged into the follicle lumen

• Iodides (I–) are actively taken into the cell, oxidized to iodine (I2), and released into the lumen

• Iodine attaches to tyrosine, mediated by peroxidase enzymes

• Iodinated tyrosines link together to form T3 and T4

• Colloid is endocytosed and combined with a lysosome

• T3 and T4 are cleaved and diffuse into the bloodstream

• T4 and T3 are transported by thyroxine-binding globulins (TBGs)

• Both bind to target receptors, but T3 is ten times more active than T4

1. Peripheral tissues convert T4 to T3

2. Negative feedback regulation of TH release

    A. Rising TH levels provide negative feedback inhibition on release of TSH (Thyroid Stimulating Hormone)

    B. Hypothalamic thyrotropin-releasing hormone (TRH) can overcome the negative feedback during pregnancy or exposure to cold

• Hyposecretion in adults—Myxedema; endemic goiter is due to lack of iodine

• Hyposecretion in infants—Cretinism

• Hypersecretion—Graves’ disease

• Produced by parafollicular (C) cells

• Antagonist to parathyroid hormone (PTH)

• Inhibits osteoclast activity and release of Ca2+ from bone matrix

• Stimulates Ca2+ uptake and incorporation into bone matrix

 • Regulated by a humoral (Ca2+ concentration in the blood) negative feedback mechanism

• No important role in humans; removal of thyroid (and its C cells) does not affect Ca2+ homeostasis

• Stimulates osteoclasts to digest bone matrix

• Enhances reabsorption of Ca2+ and secretion of phosphate by the kidneys

• Promotes activation of vitamin D (by the kidneys); increases absorption of Ca2+ by intestinal mucosa

Negative feedback mechanism:

Rising Ca2+ in the blood inhibits PTH release

• Hyperparathyroidism due to tumor

• Bones soften and deform

• Elevated Ca2+ depresses the nervous system and contributes to formation of kidney stones

• Hypoparathyroidism following gland trauma or removal results in tetany, respiratory paralysis, and death

Structurally and functionally, they are two glands in one

1. Adrenal medulla—nervous tissue; part of the sympathetic nervous system

2. Adrenal cortex—three layers of glandular tissue that synthesize and secrete corticosteroids

1. Zona glomerulosa—mineralocorticoids

2. Zona fasciculata—glucocorticoids

3. Zona reticularis—sex hormones, or gonadocorticoids

A. Regulate electrolytes (primarily Na+ and K+) in ECF

   1.Importance of Na+: affects ECF volume, blood volume, blood pressure, levels of other ions

   2.Importance of K+: sets RMP of cells

B. Aldosterone is the most potent mineralocorticoid

   1. Stimulates Na+ reabsorption and water retention by the kidneys

1. Renin-angiotensin mechanism: decreased blood pressure stimulates kidneys to release renin, triggers formation of angiotensin II, a potent stimulator of aldosterone release

2. Plasma concentration of K+: Increased K+ directly influences the zona glomerulosa cells to release aldosterone

3. ACTH: causes small increases of aldosterone during stress

4. Atrial natriuretic peptide (ANP): blocks renin and aldosterone secretion, to decrease blood pressure

Aldosteronism—hypersecretion due to adrenal tumors *Hypertension and edema due to excessive Na+

* Excretion of K+ leading to abnormal function of neurons and muscle

• Keep blood sugar levels relatively constant

• Maintain blood pressure by increasing the action of vasoconstrictors

Cortisol is the most significant glucocorticoid

• Released in response to ACTH, patterns of eating and activity, and stress

• Prime metabolic effect is gluconeogenesis—formation of glucose from fats and proteins

• Promotes rises in blood glucose, fatty acids, and amino acids

Hypersecretion—Cushing’s syndrome

• Depresses cartilage and bone formation

• Inhibits inflammation

• Depresses the immune system

• Promotes changes in cardiovascular, neural, and gastrointestinal function

Hyposecretion—Addison’s disease

• Also involves deficits in mineralocorticoids

• Decrease in glucose and Na+ levels

• Weight loss, severe dehydration, and hypotension

May contribute to:

• The onset of puberty

• The appearance of secondary sex characteristics

• Sex drive

These hormones cause:

• Blood glucose levels to rise

• Blood vessels to constrict

• The heart to beat faster

• Blood to be diverted to the brain, heart, and skeletal muscle

• Epinephrine stimulates metabolic activities, bronchial dilation, and blood flow to skeletal muscles and the heart

• Norepinephrine influences peripheral vasoconstriction and blood pressure

Melatonin may affect:

• Timing of sexual maturation and puberty

• Day/night cycles

• Physiological processes that show rhythmic variations (body temperature, sleep, appetite)

Has both exocrine and endocrine cells:

• Acinar cells (exocrine) produce an enzyme-rich juice for digestion

• Pancreatic islets (islets of Langerhans) contain endocrine cells

   1.Alpha cells produce glucagon (a hyperglycemic hormone)

  2.Beta cells produce insulin (a hypoglycemic hormone)

Major target is the liver, where it promotes:

• Glycogenolysis—breakdown of glycogen to glucose

• Gluconeogenesis—synthesis of glucose from lactic acid and noncarbohydrates

• Release of glucose to the blood

Effects of insulin:

• Lowers blood glucose levels

• Enhances membrane transport of glucose into fat and muscle cells

• Participates in neuronal development and learning and memory

• Inhibits glycogenolysis and gluconeogenesis

True or False:

PTH levels remain fairly constant with age, but lack of estrogen in older women makes them more vulnerable to bone-demineralizing effects of PTH