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48 Cards in this Set

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Hormone (definition)

chemical messenger released by one tissue into the bloodstream to have its effects at other tissues (one or more) that may be far away

What can hormones do/need?

-target tissue needs appropriate hormonal receptors to initiate effects


-may stimulate protein synthesis by activating genes in the cell nucleus


-alter synthesis of enzymes or proteins by changing the rate of transcription or translation

Modes of Intercellular communication:


Direct Communication

via "gap junctions" for transfer of ions or other chemicals, and electrical signals; physically connected cells of the same type

Modes of intercellular communication:


Paracrine

-between neighboring cells in a single tissue;


-via release of chemical messenger that affects neighbors;


-local signaling


-chemicals can be called cytokines or paracrines or local hormones

Modes of intercellular communication:


Endocrine

-uses hormones that circulate in the blood stream to communicate with cells in other tissues that posses specific receptors for the hormones

Modes of intercellular communication:


Synaptic

-limited means of communication restricted to specialized cells


-uses neurotransmitters to communicate with cells possessing neurotransmitter receptors

Similarities between endocrine vs. neural

-release chemical signals


-some hormones are neurotransmitters (NE)


-both chemicals bind to specific receptors to initiate actions


-both regulated primarily by negative feedback


-both work to preserve homeostasis by coordinating physiological functions

Differences between endocrine vs. neural

-hormones deliver via bloodstream and neurotransmitters via action potentials/synapses


-hormones are slower onset; useless if immediate effects required


-hormonal effects are long-lasting


-hormones are further-reaching; can affect many cells/tissues

Endocrine vs. Exocrine


ENDOCRINE

ductless, release secretion (hormones) into bloodstream

Endocrine vs. Exocrine


EXOCRINE

has ducts, releases various secretions onto epithelial surface (ex skin)

Classes of hormones:


Lipid Derivatives

-hydrophobic (lipid soluble)


-steroids: derived from cholesterol


i. from gonads (estrogen, androgens, progestins)


ii. adrenal cortex (mineralocorticoids, glucocorticoids, androgens)


iii. kidney (calcitriol)



Classes of hormones:


Peptide/Protein

-hydrophilic (can't cross plasma membrane)


-glycoproteins: TSH, LH, FSH, EPO, inhibin


-small proteins: ADH, oxytocin, ACTH, GH, MSH, PRL, insulin, glucagon, PTH, CT, ANP (from hypothalamus, pituitary gland, pancreas, parathyroid gland, gut)

Classes of hormones:


Amino acid derivatives

-derived from tyrosine or tryptophan


-hydrophilic


-catecholamines: E, NE, dopamine


-melatonin


-thyroid hormones *behaves like steroid hormone (binds intracellular receptors

Hormone Release

-hormone released by endocrine cells near capillaries


-enters capillaries to travel to target organs, where receptors specific for hormone are found

Hormone transport through bloodstream

-hrydophilic hormones can travel unbound in blood but short half life


-hydrophobic hormones typically use transport protein


i. albumins and globulins (plasma proteins)


i. thyroid hormone also transported bound to transport protein


i. increases hormone half life by protecting from kidneys


i. must dissociate from transport protein to enter target cells

Hormone clearance - limited life span of hormones

- degraded after binding receptor


- degraded by kidney or liver - excreted in bile or urine


- inactivated by circulating enzymes

Synergistic effects

-same time


-multiple hormones act together for greater effect


i. synergism between FSH and testosterone on sperm production

Permissive effects

- sequential


- one hormone enhances targets response to a second later hormone


i. estrogen prepares uterus for action of progesterone

Antagonistic effects

-one hormone opposes action of another


i. insulin lowers blood glucose and glucagon raises it


i. calcitonin lowers blood calcium and parathyroid hormone raises it

Hormone receptors

act like switches to turn on or off cellular activity



Specificity

hormones bind to receptors that are specific for that hormone

Saturation

there is a finite number of receptors to bind hormone

Receptors may be located:

-on cell surface: facing outside of cell; membrane bound, cell surface receptor


-inside cells: intracellular, may be in cytoplasm or nucleus

Mechanisms of hormone action:


Intracellular receptors to alter gene activity

-used by steroid receptors which can easily cross membrane and enter cell


1. binds to receptors in the cytoplasm (which then moves to nucleus) or nucleus


2. hormone-receptor complex can activate or deactivate different ones (so can change the rate of DNA transcription, change protein synthesis, etc)


3. also mechanic used by thyroid hormones which probably uses a carrier protein to get across membrane into the cells- bind to receptors in the nucleus or mitochondria to change metabolic activities of cells (eg: may increase synthesis of Na-K ATPase or myosin) or the rate of ATP production (if mitochondria)

Mechanisms of hormone action:


Cell membrane receptors

1. for catecholamines, peptides - not lipid-soluble, so can't cross the membrane


2. cell surface membrane receptors - no direct effect of hormones! hormones are the first messengers, result in production of second messengers, which effect change in the cell


3. link between the first and second messenger involves G protein (enzyme complex, binding GTP, coupled to the membrane receptor, so these receptors are G-protein linked membrane receptors)


4. binding of hormone to receptor causes cascades of reactions, (intracellular cascade), resulting in more than on active second messenger


5. involves amplification of the original signal, one hormone molecule can produce lots of second messenger molecules

Most important second messengers:

cAMP - cyclic AMP


cGMP - cyclic GMP


calcium


DAG - diacylglycerol


IP3 - inositol triphosphate



Examples of metabolic reactions triggered by second messengers:

-activation of kinases, which phosphorylate to cause changes in:


i. synthesis of proteins


ii. secretion


iii. change membrane potentials by opening or closing ion channels

3 common intracellular cascades triggered by hydrophilic hormones:


Stimulation of cAMP cascade

1. hormone binds to receptor and activates adenylate cyclase, the enzyme catalyzing the conversion of ATP to cAMP


2. cAMP acts as 2nd messenger to activate kinases, enzymes that phosphorylate - target of kinases can be ion channel, activating other enzymes


3. actions of cAMP terminated by phosphodiesterase, enzyme that activates cAMP by converting it to AMP


4. mechanism for E and NE (on beta receptors), calcitonin, PTH, ADH, ACTH, FSH, LH, TSH, glucagon

3 common intracellular cascades triggered by hydrophilic hormones:


Inhibition of cAMP cascade

1. hormone binds receptor, which is linked via G protein to phosphodiesterase (PDE), enzyme that inactivates cAMP by converting it to AMP


2. cause cAMP levels in cell to decline, and whatever other reactions would be activated by cAMP can no longer occur, so inhibitory effect in the cell


3. mechanism for E and NE on alpha 2 receptors

3 common intracellular cascades triggered by hydrophilic hormones:


Calcium- related second messenger pathways

1. activated G protein can trigger opening of Ca2+ channels and/or release of Ca from intracellular stores


2. hormone binds receptors, activated G protein, which activates phospholipase C:


- activates diacylglycerol (DAG) with Ca activates PKC which phosphorylates lots of things, Ca channels (opens them), positive feedback to increase Ca, especially along with IP3 activation


-activates inositol triphosphate (IP3) which causes the release of Ca from intracellular stores


- calcium can then bind to calmodulin and act as 3rd messenger causing other effects in cell mechanism for E and NE on alpha 1 receptors, oxytocin, hypothalamic regulatory hormones

Hypothalamus

-highest level of endocrine control


-coordinates actions of endocrine and nervous systems


-secretes regulatory hormones that control release of other hormones from the anterior lobe of the pituitary gland (which in turn control thyroid, adrenal cortex, and gonads)


-produces hormones ADH and oxytocin, transports them down axons to the posterior pituitary gland, where it can be released into the bloodstream


-has autonomic centers to control the sympathetic output of the adrenal medulla (E, NE)

Pituitary Gland:


Hypophysis

-connected to the hypothalamus by the infundibulum


-7 peptide hormones release by ant pit


-2 peptide hormones released by post pit


-all bind to membrane rec and all use cAMP as their 2nd messenger



Posterior Pituitary


Neurohypophysis

-contains axons of hypothalamic neurons


-supraoptic and paraventricular nuclei of hypothalamus produce ADH and oxytocin, respectively, and transport it down their axons to the post pit

ADH - Antidiuretic hormone

-release in response to increased electrolytes in blood or decreases in blood pressure or volume


i. increased electrolytes directly stimulate hypothalamic neurons (osmoreceptors) to release ADH


ii. acts to decrease H2O loss at kidneys


iii. at high concentrations, causes vasoconstriction to increase blood pressure


iiii. diabetes incipitus - not enough ADH released, so lots of dilute urine, and thirst

Oxytocin - OT

-stimulates uterine smooth muscle contraction for labor and delivery

-acts on mammary glands following delivery fro milk (ejection)


-in males and females, OT may also have a role in sexual arousal and orgasm



Anterior Pituitary


Adenohypophysis + Intermediate lobe

Hypophyseal portal system: direct circulatory communication between hypothalamus and ant pit


- hypothalamic neurons secrete regulatory hormones (TRH, CRH, GnRH) into interstitial fluid near median eminence (base of hypothalamus, at the top of the infundibulum)


- hormones enter capillary network in this region because they are fenestrated capillaries, then travel down into ant pit and enter another capillary network (so these cap bed form a portal system)


- ensures that hormones from hypothalamus aren't diluted or "lost" on the way to the ant pit *one way communication*

Hormones of Ant Pit

-releasing and inhibiting hormones


-controlled with negative feedback

TSH - Thyrotropin

-stimulated by TRH from hypothalamus


-stimulates release of thyroid hormones and prolactin



ACTH - Adrenocorticotropin

-stimulated by CRH from hypothalamus


-stimulates release of steroid hormones of the adrenal cortex (ex glucocorticoids)

FSH - Follicle stimulating hormone

-gonodotropin


-stimulated by GnRH from hypothalamus


-promotes follicle development in females, secretion of estrogens


-stimulates sustentacular cells in tests to mature sperm


-inhibited by inhibin, a hormone produced by ovaries and testes

LH - Lutenizing hormone

- gonadatropin


-stimulated by GnRH from hypothalamus


-induces ovulation and promotes secretion of progestins


-it stimulates the production of androgens in males

PRL - Prolactin

-works to stimulate development of mammary glands and milk production following delivery


-may help regulate androgen production in males

GH - Growth Hormone

-somatotropin


-stimulates growth by increasing protein synthesis


-especially sensitive are skeletal muscles and bones/cartilages

Regulation of hormone release:


Negative feedback

-can get decrease of at levels of:


i. hypothalamus (decreasing releasing hormones)


ii. anterior pituitary (decrease stimulating hormones


Examples:


- CRH - ACTH - cortisol


TRH - TSH - T3/T4


- GnRH - FSH or LH - sex hormones

Thyroid Gland

-composed of thyroid follicles, spheres of simple cuboidal epithelium, surrounding a cavity containing a viscous fluid called colloid

Thyroid gland (continued)

- follicular cells produce a precursor protein, thyroglobulin, secrete into colloid


-iodide ions taken in from diet, transported to thyroid, carrier proteins move it into the colloid


-iodide converted to iodine and attached to thyroglobulin


-grouped together to have T4 - thyroxine or T3 - triiodothyronine


-released in response to TSH, which stimulates I- uptake into the cells

To release thyroid hormones:

-thyroglobulin endocytosed into follicle cells


-lysosomal enzymes break down the thyroglobulin to release T3 and T4


-T3 and T4 diffuse across basement membrane and into circulation (90% T4, 10% T3)


- ~70% T3 and T4 attach to thyroid binding globulins (TBGs)

Functions of thyroid hormones:

-cross cell membranes, binds to cytoplasmic receptors, mitochondrial receptors, and nuclear receptors


-when bound to cytoplasmic receptors, are in storage


-when bound to mitochondrial receptors, increase rate of ATP production


-when bound the nuclear receptors, activate genes to increase metabolism (ex Na-K ATPase) enzymes involved in glycolysis and ATP production


-T3 is the more functional from, so use this first and then convert T4 to T3