Endocrinology week 1

Start Studying!

Terms

undefined, object

copy deck

endocrine gland: a ductless gland whose secretions (hormones) are released into the vascular system for an action on distant cells (target cells)
neurohormone: a hormone secreted by a nerve cell, released from nerve endings into the blood stream, and carried to another area where it exerts specific effects on target cells
what are the three major categories of hormones?: (1) peptide

(2) biogenic amines

(3) steroid hormones
peptide hormone examples: hypothalamic, anterior pituitary, posterior pituitary and pancreatic hormones
biogenic amines: amino acid derivatives

e.g. thyroid hormones and catecholamines
steroid hormones: based on the 17 carbon aromatic cyclopentanoperhydrophenanthrene nucleus, among which relatively minor chemical differences are associated with marked differences in biological activity

e.g. adrenal cortex, reproductive gland hormones and the active metabolites of vit D
biosynth of peptide hormones: synth by rough ER as pre-pro-hormone
biosynth of amine hormones: synth from tyrosine through a series of enzymatic rxns by smooth ER and mitochondria
biosynth of steroid hormones: synth from cholesterol through a series of enzymatic rxns by smooth ER and mitochondria
transport of hormones in blood: - steroid and thyroid hormones circulate bound to specific globulins

- with few exceptions (IGF-1) peptides and protein hormones circulate unbound (also catecholamines)
in what two ways are hormones measured?: (1) radioimmunoassay

(2) immunocytochemistry -- localization of hormones in tissues of origin and action
what are the four major functions of hormones:: (1) endocrine system helps initiate, mediate, and regulate the processes of growth, differentiation, development, maturation, and senescence

(2) maintenance of homeostasis, fluid and electrolyte balance

(3) regulation of cellular metabolism (fats, carbs, proteins)

(4) sexual development and function, lactation, behavior
name two similarities between the nervous and endocrine systems: (1) each synthesizes and releases specific chemical agents which are capable of influencing other cells by interacting with specific receptors

(2) both neurons and endocrine cells generate electrical potentials and can be depolarized
waddya think?: get it?
name six hormones that originate in the hypothalamus: (1) TRH

(2) CRH

(3) LHRH

(4) GHRH

(5) somatostatin

(6) dopamine
name seven hormones that originate in the anterior pituitary: (1) GH

(2) prolactin

(3) TSH

(4) ACTH

(5) LH

(6) FSH

(7) MSH
name two hormones that originate in the posterior pituitary: (1) ADH or vasopressin

(2) oxytocin
name one hormone that is released from the parathyroid gland: PTH
name one hormone that originates in the parafollicular cells of the thyroid gland: calcitonin
name one hormone that originates in the parathyroid gland: PTH
name two hormones that originate in the adrenal cortex: glucocorticoids, aldosterone
name two hormones that originate in the adrenal medulla: Epi, NE
name three hormones that originate in the pancreas: (1) insulin

(2) glucagon

(3) somatostatin
name one hormone that originates in the skin, liver, kidney: vit D
name two hormones that originate in the placenta: Human Chorionic Gonadotropin (hCG)

Human Placental Lactogen (hPL)
mechanism of steroid hormone action: (1) endocrine gland + stimulus --> inc steroid release

(2) steroid diffuses through the cell membrane into the cytoplasm of target cell

(3) steroid binds to cytoplasmic and/or nuclear receptors forming a steroid-receptor complex

(4) dimerization of the liganded receptor enables the activated steroid-receptor complex dimer to bind tightly to specific DNA sequences, called Steroid Responsive Elements (SRE), and interact with coregulator proteins thus activating or suppressing transcription (mRNA) of genes under the control of steroid hormones

(5) mRNA is translated into specific proteins

(6) inc specific proteins --> inc physiological responses
steps in cAMP dependent mechanism of peptide hormone action: (1) endocrine gland + stimulus --> inc release of hormone (1st messenger)

(2) hormone + target cell membrane receptor --> inc hormone-receptor complex

- peptide hormone receptors are membrane-bound, mobile, glycosylated, large peptides

(3) inc hormone-receptor complex --> inc activation of G-protein --> inc adenylyl cyclase activity

- hormone binding --> GDP-GTP exchange --> binding of GTP to alpha subunit resuls in dissociation of G-alpha from Beta-gamma --> G-alpha interacts with adenylyl cyclase

(4) ATP + adenylyl cyclase --> inc cAMP + Pi

(5) specific protein kinase(s) are activated by cAMP

(6) the activated protein kinases catalyze phosphorylation of enzymes by ATP resulting in physiological responses
cAMP is inactivated by what enzyme?: phosphodiesterase
steps in calcium-phospholipid mechanism: (1) hormone + membrane receptor --> inc hormone-receptor complex

- formation of high-affinity hormone-receptor complex results in transmission of the signal through a G-protein (Gq) to the enzyme phospholipase c

(2) activation of the cell membrane enzyme phospholipase c

(3) conversion of PIP2 --> IP3 and 1,2 diacylglycerol

- IP3 enhances intracellular calcium and calcium-calmodulin processes

- 1,2 diacylglycerol activates the enzyme PKC which catalyzes the phosphorylation of proteins by ATP
steps in internalization of peptide hormones: (1) endocrine gland + stimulus --> inc hormone

(2) hormone binds to cell membrane receptor

(3) hormone-receptor complexes are clustered on the membrane

(4) membrane containing aggregated hormone-receptor complexes begin to fold inward forming a coated pit

(5) coated pits are internalized into the cell forming endocytic vesicles called endosomes

(6) endosomes (by a ATP-dependent process) may facilitate the release of ligand from receptor. Ligand and receptor are sorted, and the ligand is degraded by lysosomal enzymes (hydrolases). The internalized receptor may be recycled to the cell surface or degraded by lysosomal enzymes
what are the four main steps in the biosynthesis of thyroid hormones?: (1) iodine accumulation

(2) coversion of I- (iodide) to I2 (iodine)

(3) organification

(4) coupling rxns
what drugs inhibit the coversion of iodide to iodine?: PTU and methimazole
coupling rxns -- how are T3 & T4 formed?: T3 is formed by the coupling of one MIT & one DIT

T4 is formed by the coupling of two DITs
steps in the hydrolysis of thyroglobulin: droplets of colloid are taken back into the follicular cells by pinocytosis and coalesce with lysosomes. Lysosomal enzymes release the iodinated constituent from peptide bonds by proteolysis

(1) inc proteolysis (stim by TSH)

(2) inc liberation of T3 & T4

(3) inc liberation of inactive I- compounds MIT & DIT

(4) MIT & DIT --> deiodinase --> I- --> reuptake by the thyroid gland
what are the T3/T4 binding proteins (plasma): TBG
TBPA
Albumin
large dose of T4: inc BMR seen after 2-3 days and reaches a max in 10-12 days
large dose of T3: inc BMR seen after 6-12 hours and reaches a max in 2-3 days
what are the four specific actions of TH?: (1) normal bone, skeletal, and mental development

(2) metabolism effects: calorigenic, thermogenic, carb/protein/lipid metabolism

(3) promotes normal neuronal development

(4) cardiovascular effects -- inc rate and strength of heartbeat, ventilation, and CO
TSH fxns: stimulates growth and metabolism of the thyroid gland including biosynth of T3, T4, and TG
inc TRH --> ? TSH: inc TRH --> inc TSH
inc somatostatin --> ? TSH: inc somatostatin --> dec TSH
what does prolonged and excessive TSH stimulation of thyroid gland result in?: goiter
list the three ways you can have a hypothyroid goiter: (1) administration of CNS- or HCLO4-

- T/S ratio 1:1 (preventing iodide access to thyroid gland by blocking iodide pump)

- No TH formed (dec TH, inc TSH)

(2) administration of PTU

- inhibits coversion of iodide to iodine

- No TSH is formed (dec TH, inc TSH) and goiter results with the notable exception that T/S ratio becomes very high (100:1 or 200:1)

(3) I- deficiency

- little TH is made and a goiter results (dec TH, inc TSH)
hyperthyroid goiter: LATS is an antibody against the TSH receptor which binds to TSH receptor and mimics TSH actions on thyroid gland TH synthesis

inc LATS, inc T3/T4, dec TSH
euthyroid goiter: iodine deficiency, inc TSH to compensate for dec TH
hypothalamic nuclei - comprised of - two nuclei: are comprised of cell bodies of neurosecretory cells

(1) surpraoptic nucleus

(2) paraventricular nuclei
hypothalamo-neurohypophyseal tract - aka - comprised of / fxn: aka pituitary stalk

comprised of axons of neurosecretory cells

site of transport of prohormone by axoplasmic flow, and post ribosomal processing to actual hormone and its associated products; contains glycoprotein enriched material that is termed neurosecretory material (NSM)
posterior pituitary gland - aka - comprised of / fxn: aka pars nervosa

comprised of terminals of the neurosecretory cell and is the site of storage and release of hormones and associated products
what are the hormones of the posterior pituitary?: ADH and oxytocin
where does synth of vasopressin & oxytocin occur?: occurs in the hypothalamic nuclei (supraoptic & paraventricular)
pre-propressophysin: pre-prohormone, precursor to vasopressin

signal peptide + vasopressin + neurophysin II + glycoprotein
pre-prooxyphysin: pre-prohormone, precursor to oxytoxin

signal peptide + oxytocin + neurophysin I
what is involved in the initial processing of pre-prohormones?: removal of signal peptide --> prohormone
where does postribosomal proteolytic processing and axoplasmic flow of vasopressin and oxytocin occur?: in the hypothalamo-neurohypophyseal tract
what are the two physiologic actions of vasopressin and which is major?: (1) vasopressor action

- involves V1 receptor and a Ca2+ dependent form of signal transduction

(2) antidiuretic action (major)

- reabsorption of water in distal convoluted tubule and collecting duct
what is the mechanism of vasopressin action in kidney?: antidiuretic action of vasopressin is adenylate cyclase mediated and involves V2 receptors

(1) V2 receptors on blood surface of nephron target cells generate cAMP

(2) signal transduction leads to inc protein phosphorylation and water permeability at the luminal surface of the target cell

(3) permeability change is due to altered activity and/or number of water channels (aquaporin)
what are the two signals that stimulate vasopressin release? Compare the two in terms of sensitivity and potency.: Hypovolemia -- more potent / less sensitive

Hyperosmolarity -- more sensitive / less potent
what mediates the hypovolemic response (vasopressin release)?: left atrial stretch receptors and baroreceptors

- stretch receptors lead to inc firing of vagal inhibitory neurons leading to dec vasopressin release (opposite is true in hypovolemia)
what mediates the hyperosmolarity response (vasopressin release)?: hypothalamic osmoreceptors
what are the two separate endocrine organs that make up the adrenal gland and what are their embryological origins?: (1) adrenal cortex -- mesoderm

- lipid laden epitheloid cells interspersed with sinusoids

(2) adrenal medulla -- ectoderm

- hormone secreting cells are modified postganglionic sympathetic neurons (chromaffin cells)
adrenal cortex regions / percentages: (1) zona glomerulosa 15% outer

(2) zona fasciculata 80% middle

(3) zona reticularis 5% inner
glucocorticoids: e.g. cortisol

elevate BP among other effects
mineralcorticoids: e.g. aldosterone

fxn to conserve sodium
what does the adrenal medulla produce?: catecholamines, hormones derived from the AA tyrosine
what is the major catecholamine secreted by the adrenal medulla?: epinephrine
what are the two prominent corticosteroid binding proteins in plasma and what percentages of cortisol do they bind?: (1) albumin -- low affinity / high capacity -- 15%

(2) CBG -- high affinity / limited capacity -- 75-80%
what are the fxns of corticosteroid plasma proteins?: (1) inc solubility of steroid in plasma

(2) controls the distribution of steroids to tissues
describe the circadian rhythm of ACTH/cortisol: highest in morning upon waking

lowest at the very end of the day (1 AM)
when can circadian rhythm of ACTH/cortisol be absent?: in adrenocortical hypersecretion disorders (e.g. Cushing's syndrome)
what are the four stimuli for aldosterone secretion, and which is major?: (1) dec BV (major)

(2) dec plasma Na+, inc plasma K+

(3) very high doses of ACTH

(4) stimulation of symp innerv of kidney
alternate renin-angiotensin pathway: (1) A-I converted to a nonapeptide (Des Asp1) A-I by an aminopeptidase in plasma and tissues

(2) (Des Asp1) A-I is converted to the heptapeptide A-III

- A-III as potent as A-II in stimulating aldo release but possesses only 50% of its pressor activity
21 carbon steroids: steroid nucleus, methyls 18 and 19, and a 2 carbon sidechain (carbons 20 and 21)

progestins (e.g. progesterone)

corticosteroids (e.g. cortisol, aldosterone)
19 carbon steroids: steroid nucleus, methyls 18 and 19

androgens (e.g. DHEA, testosterone)
18 carbon steroids: steroid nucleus, methyl 18

estrogens (e.g. estradiol-17Beta)
desmolase rxn: Cholesterol (27C) --> delta5 pregnenolone (21C) + isocaproic acid (6C)

- cholesterol side chain cleavage is the site of ACTH action
pathway from delta5 pregnenolone --> aldo: (1) delta5 pregnenolone --> progesterone

- 3 Beta-ol dehydrogenase:isomerase

(2) progesterone --> 11-deoxycorticosterone (DOC)

- 21-hydrolylase
- DOC is a potent mineralcorticoid

(3) DOC --> corticosterone

- 11Beta-hydroxylase
- corticosterone exhibits both glucocorticoid and mineralcorticoid activities

(4) corticosterone --> 18-hydroxycorticosterone

- 18-hydroxylase
- site of action of A-II and A-III

(5) 18-hydroxycorticosterone --> aldosterone

- 18-hydroxysteroid dehydrogenase
- aldosterone is the most potent naturally ocurring mineralcorticoid
17alpha-hydroxylase pathway - starts with? ends with?: delta5 pregnenolone --> cortisol
17alpha-hydroxylase pathway: (1) 17alpha-hydroxylase (unique to ZF & ZR)

delta5 pregnenolone --> 17alpha hydroxypregnenolone

progesterone --> 17alpha hydroxyprogesterone

(2) 3-Beta-ol dehydrogenase:isomerase

delta5 pregnenolone --> progesterone

17alpha hydroxypregnenolone --> 17alpha hydroxyprogesterone

(3) 21-hydroxylase

17alpha hydroxyprogesterone --> 11-deoxycortisol

(4) 11Beta-hydroxylase

11-deoxycortisol --> cortisol

- cortisol exhibits both glucocortisoild and mineralcortisoid activities

- cortisol is the principal glucocorticoid secreted by the adrenal cortex
adrenal androgen and estrogen production pathway: (1) 17alpha-hydroxylase

generating 17alpha-hydroxyprenenolone, and 17alpha-hydroxyprogesterone

(2) C-17, 20 lyase

17alpha-hydroxypregnenolone --> DHEA

17alpha-hydroxyprogesterone --> androstenedione

DHEA is a weak androgen, is a major source of androgen in the female

(3) 3Beta-ol dehydrogenase:isomerase

DHEA --> androstenedione

androstenedione is a weak androgen (immediate precursor to testosterone)

(4) 17Beta-hydroxysteroid dehydrogenase

androstenedione --> testosterone

(5) Aromatase

testosterone --> 19 nortestosterone

19-nortestosterone --> estradiol 17Beta
waddya think?: get it?
what is the major rxn of the degradation of corticosteroids?: involves modification of corticosteroids by liver

major rxn is A-ring reduction:

conversion of delta4,3-ketone to a tetrahydroderivative of the compound
MSH fxn: darken skin by dispersion of melanosomes
Beta-LPH fxn: lipolytic
Beta-Endorphin: exhibit endogenous opiate activity and may play a role in mood states and analgesia

B-Endorphin release is stimulated by CRH and is inhibited by glucocorticoids, as is ACTH
mineralcorticoids exert their effect through Type I or Type II receptors?: Type I
glucocorticoids exert their effect through Type I or Type II receptors?: Type II
cushing's syndrome: characterized by elevated levels of cortisol and the absence of diurnal variation in plasma cortisol
cushing's syndrome three possible etiologies: (1) primary hypercortisolism

- cortisol secreted by adrenal tumor

(2) secondary hypercortisolism

- ACTH hypersecretion from the anterior pituitary (Cushing's disease)

(3) Iatrogenic Cushing's syndrome (physician-induced)

- results from exogenous ACTH or corticosteroids
possible etiologies of hypocortisolism: (1) primary hypocortisolism

- massive lesions in both adrenals (Addison's disease)

- deficiencies in steroidogenic enzymes (Congenital Adrenal Hyperplasia)

(2) secondary hypocortisolism

- panhypopituitarism

- isolated ACTH deficiency

- physician-induced (iatrogenic) after termination of long-term corticosteroid therapy
where is GH synth?: synth as a preprohormone by somatotrophs of the anterior pituitary
five physiological actions of GH: (1) promotes linear growth, maintains lean body mass

(2) inc protein, RNA and DNA synth in most tissues (anabolic)

(3) inc fat utilization (lipolytic) and dec carb utilization (hyperglycemia)

(4) inc calcium and phosphate retention

(5) stimulates release of somatomedin 'C' or insulin-like growth factor I (IGF-I) from the liver, fibroblasts, muscle, etc

- IGF-I with GH stimulates skeletal (cartilage) growth by stimulating chondrocyte mitosis, collagen synth, and matrix synth
- IGF-I production is dec with low insulin and low dietary intake
mechanism of GH action: binding of GH to extracell domain of its recept results in the dimerization of the receptor with rapid phophorylation and activation of Janus kinases on the cytoplasmic domain

These result in phosphorylation of STAT, IRS, GRB2, and PLC pathways and stimulation of gene expression
Kwashiorkor: disease associated with starvation (particularly protein deficiency) and is characterized by high GH levels (possibly due to hypoglycemia) and protein depletion
sources of somatostatin: hypothalamus, D cell of pancreatic islet, GI-tract
physiologic action of somatostatin: (1) inhibits release of GH, prolactin, TSH, insulin, glucagon, GI hormones

(2) dec GI blood flow and motility, and inhibits secretion of gastric acid and pepsin

(3) inc GI water and electrolyte absorption
mechanism of action of somatostatin: inc somatostatin --> dec intracell calcium --> dec cAMP and blockage of K channel
where is prolactin produced?: produced by mammotrophs of the anterior pituitary as a preprohormone
physiologic actions of prolactin: (1) initiates and maintains milk production, development of breasts

(2) influences immune responses and reproductive function
in what ways does the hypothalamus regulate prolactin synth and release: (1) dopamine and somatostatin supress synth and release of prolactin

(2) TRH promotes prolactin release
mechanism of prolactin action: prolactin binds to PM receptors and activates cytoplasmic Janus kinases. These phosphorylate STAT proteins that stimulate expression of genes such as milk proteins casein, lactoalbumin, etc

Start Studying!

Deck Info

Number of cards 100