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Kaplan - Endocrinology - Part I


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What are the lipid soluble hormones?
Steriod hormones and thyroid hormones.
What are the water soluble hormones?
peptide hormones and biogenic amines
Describe the receptor location, mechanism of intracellular action, storage, plasma transport, and half-life of Lipid soluble and water soluble hormones.
Lipid soluble hormones:
receptors on inside the cell, usually in the nucleus
intracellular action is by production of new proteins, there is no storage of steroids, but there is storage of THYROID HORMONES (not in vesicles but covalently bound to proteins)
They are transported in the plasma attached to proteins that serve as carriers. The exception to this rule is the ADRENAL ANDROGENS.
The half life of lipid soluble hormones is very long (hours, days) due to their binding to the protein carrier.

Water soluble hormones:
Receptors are on outside surface of cell
Intracellular action is thru 2nd messengers...mainly cAMP...except insulin which uses membrane bound tyrosine kinase. Second messengers then modigy protein which already exist in the cells.
Peptide PROhormones are stored in vesicles WITH AN ENZYME. It is not until release that he enzyme splits the PROhormone to create the active hormone and an inactive hormone.
Peptide are transported in the plasma freely dissolved and not attached to anything.
The half life of water soluble hormones in very short.
Although adrenal androgens are steriods, why are they water soluble?
Before they are secreted they are conjugated with sulfate and they makes them water soluble
Which hormone has the longest circulating half life and why does it?
T4 because it is very strongly bound to protein in circulation
Which water soluble hormone does not travel freely dissolved in plasma and what does htis give it
(Insulin-like growth factor - 1) IGF-1 is strongly attached to protein and thus has a long half life
What determines the half life of water soluble hormones?
The molecular weight. the larger the size, the longer the half life.
What is the largest circulating water soluble hormone?
Human chorionic gonadotropin (hCG)
The liver produces proteins that bind lipid soluble hormones for transport in the plasma. What are four main examples?
Mainly Albumin, but also
1. Cortisol binding globulin
2. Thyroid binding globulin
3. Estrogen/testosterone binding globulin
Does the total amount of hormone in the blood or the active/free hormone control negative feedback?
Free hormone only controls neg. feedback and thus is the only one precisely regulated.
What is one common hormone that stimulates the liver to produce more globulin?
Where does ACTH have it's effect? what is effect

adrenocorticotropic hormone
adrenal cortex

it increases production of steriod hormones
Where does LH have it's effect? what is effect

luteinizing hormone
gonadal tissue

it increases production of steriod hormones
What is the definition of permissive action?
A phenomenon in which one type of hormone must be present before another hormone can act; for example, to prevent hypoglycemia, cortisol must be present for glucagon to carry out glycogenolysis.
What is the relationship between cortizol and glucagon and why?
cortizol must pbe present for glucagon to carry out glycogenolysis. this is to prevent hypoglycemia.
What is characteristic of the hormones produced in the hypothalamic-anterior pituitary system?
where synthesized?
where stored?
where released?
-all water soluble
-synthesized in the neuron cell body
-stored and released from the nerve terminals
What hormones are released from the hypothalamus?
thyrompin-releasing hormone (TRH),
corticouopin-releasing hormone (CRH), growth hormone releasing hormone
(GHRH), somatostatin, and prolactin-inhibiting factor (PIF) are
synthesized in neuron4 cell bodies in the ventmmedial, arcuate, and paraventricular
nuclei; ganadotropin-releasing hormone (GnRH) is synthesized
in the preoptic nucleus
What does each of the following addreviations stand for?
TRH (2)
CRH (2)
Thyrotropin-releasing hormone
corticotropin-releasing hormone
growth hormone-releasing hormone
prolactin-inhibiting factor
gonadotropin-releasing hormone
thyroid-stimulating hormone or thyrotropin
corticotropin or adrenocorticotropic hormone
luteininzing hormone
follicle-stinulating hormone
growth hormone
LH and FSH are both stimulated to be relased by GnRH from the hypothalamus. Are they individually controlled somehow?
yes, although they are stimulated by the same hormone, LH and FSH are individually controlled somehow.
Which nuclei of the hypothalamus produce TRH, CRH, GHRH, somatostatin, and PIF
neuronal cell bodies in the arcuate and paraventricular nuclei.
Which hypothalmic nuclei producesGnRH
preoptic nucleus
nerve endings come together in which area of the hypothalamus?
median eminence
Hormones from the hypothalamus are secreted into what on their way to the anterior pituitary?
hypophyseal portal system
Hypothalamic hormones bind to receptors on cells in the anterior pituitary and cause secretion of what hormones?
and prolactin
What effect does each hypothalamic hormone have o nthe anterior pituitary?

look at image
In addition to PIF, what is another hormone that inhibits the release of prolactin.
What adrenal hormone is released by the zona glomerulosa and what is it's release controlled by?
aldosterone and it is mainly controlled by angiotensin II, but is also partly controlled by [K+]. When K+ conc. goes up the secretion of aldosterone goes up.
what are the four regions of the adrenal gland, from outermost to innermost?
zona glomerulosa, zona fasciculata, zona reticularis, medulla
What hormone does the Zona fasciculata secrete and what is it controlled by?
cortisol and it's secretion is controlled by ACTH
What hormone does the Zona Reticularis secrete and what is it controlled by?
The Zona reticularis secretes androgens and it's secretion is controlled by ACTH
What hormone does the medulla secrete and what is it controlled by?
Epinephrine which is controlled by the autonomic nervous system.
Which hormone regulates the release of testosterone and where is the testosterone produced and released from?
LH stimulates the testes to realease testosterone, but LH has no effect on the adrenal androgens.
What is primary adrenal insufficiency also known as?
Addison's Disease
What happens if you lose secretion from the zona glomerulosa?
you lose production of aldosterone, the meneralocorticoid, and thus you do not retain sodium anymore. As you lose sodium, water follows sodium and you become dehydrated.
What happens if you lose secretion from the zona fasiculata, zona reticularis?
you lose you secretion of cortisol, the glucocorticoid, and thus you have circulatory failure do to catacholamines not able to exert their normal vasoconstrictive action. you also are not able to mobilized energy sources...remember the permissive action of cortisol and glucagon, however the cortisol release is not essential for life unless you are fasting and have fatal hypoglycemia.
What happens if you lose secretion from the medulla?
you lose secretion of epinephrine, the catacholamine, and thus you cannot mobilize glycogen or fat during exercise or cold exposure, however it is not essential for life.
what is the starting point for all steroid hormone production?
What is the first step in the synthesis of steroid hormones?
the what is this step catalyzed by?
why is this step inportant
The conversion of cholesterol into pregnenolone.
catalyzed by desmolase
the step is important because it is a rate limiting step in most tissues
Draw the biosynthetic pathway for the production of aldosterone in the zona glomerulosa.

look at pic
Draw the biosynthetic pathway for the production of cortisol and adrenal androgens in the zona fasiculata and the zona reticularis.

look at pic
If a tissue has what enzyme it will convert progesterone to 11-Deoxycorticosterone?
21 Beta-Hydroxylase
Why is 11-Deoxycorticosterone important
it is important because it is a weak mineralocorticoid, circulating hormone and it is the intermediate between progesterone and corticosterone in the production of aldosterone
What enzyme converts weak mineralocorticoid into corticosterone, a weak glucocorticoid?
11 Beta-Hydroxylase
What enzyme works on both pregnenolone and progesterion and puts a hydroxyl at position 17. This action produces what type of molecule
17 Alpha-Hydroxylase

it produces 17-hydroxy (OH) Steriods
What is the only 17-OH steriod that is a hormone?
What two enzymes are required for the production of both cortisol and aldosterone (and are therefore present in both the zona glomerulosa and zona fasciculata)?
21 Beta hydroxylase
11 Beta hydroxylase
What hormone is not required for the production of aldosterone, but is required for the production of cortisol and all of the androgens and estrogens?
17 alpha hyroxylase
What enzyme splits off two carbon atoma from the C21 steroids to produce the C19 steriods?
What type of steroids are the C19 steriods?
What type of chemical group does it place at position 17?
17, 20 lyase cleaves the two carbons and produces the C19 steriods which are the androgens.
It places a keto group at position 17.
What are the two 17 keto steriods produced by 17, 20 lyase?
What two androgens are secreted by the adrenal tissue, known as ADRENAL ANDROGENS?
What is the MAIN androgen secreted by the adrenal glands?
Before secretion adrenal androgens DHEA and A conjugated with what which makes them what?
the are conjugated with sulfate which makes them water soluble
What tissue has the enzymes which are able to convery DHEA and A in to testosterone?
Leydig cells of the testes.
What androgens will the Leydig cells release into circulation.
the DHEA and A is made in the Leydig cells but is not released into the circulation.
If the leydig cells did not have the enzyme to convert the DHEA and A into testosterone what would they do?
the would release the DHEA and A into the circulation
How do the ovaries differ from the leydig cells of the testes?
The ovaries contain all of the enzymes as the testes, but it also contains an enzyme, aromatase, which converts the androgens to estrogen
Which enzyme in the ovaries converts the androgens in estrogens?
if the ovaries lack aromatase what will they do?
they would no longer secrete extrogen but would secrete testosterone.
The first step in all tissues secreting steroid hormones is the conversion of what to what and it involves what enzyme?
chomesterol is converted to pregnenolone by desmolase.
What substances does the zona glomerulosa release?
what about the zona fasiculata, reticularis?
zona glomerulosa:

zona fasiculata, reticularis:
11-deoxycorticosterone (weak mineralocorticoid)
corticosterone (weak glucocorticoid)
adrenal androgens (DHEA and A)
What is the hormone that produces the negative feedback on the production of ACTH from the anterior pituitary?
circulating glucocorticoids, mainly the cortisol, but the other circulating glucocorticoid is 11-Deoxycorticosterone
What is the most common adrenal enzyme deficiency?
21-Betahydroxylase deficiency
In what tissues is 21-Betahydroxylase found?
zona glomerulosa, fasiculata, and reticularis
What is the effect of a 21-Betahydrogenase deficiency?
Loss of mineralocorticoids, resulting hte Loss of sodium and thus fluids, and loss of the glucocorticoids, which results in loss of negative feedback to the ant. pit. and thus there is a significant increase in ACTH secretion from ant. pit.
What is the effect of increased ACTH from the anterior pituitary gland
causes adrenal hyperplasia and overproduction of all compounds produced before the 21-betahydrogenase blockage. This leads to an overproduction of the adrenal androgens.
What tissues are affected by 11-Betahydroxylase deficiency?
zona glomerulosa, fasiculata, and reticularis
11-Betahydrogenase has an effect on what hormones.
it does not stop the production of the weak mineralocorticoid (11-deoxycorticosterone)
has an effect on secretion of aldosterone, and the major and minor glucocorticoids, leading the to over production of ACTH. and thus overproduction of androgens.
Bodily effects of 11-Betahydrogenase bodily effects.
Increased secretion of the weak mineralocorticoid can lead to hypertension.
What is one adrenal related way the body combats the hypertension produced in 11-betahydrogenase deficiency?
The kidney will stop their secretion of renin and this will stop the production of angiotensin II, which stimulates the zona glomerulosa. This basically shuts down all processes in the zona glomerulosa.
What tissues are affected by a 17-alpha hydroxylase deficiency?
zona fasiculata, zona retularis, leydig cells of testes, and overies
What hormone deficiencies will you see in a 17-alphahydroxylase?
Cortisol and all androgens, and estrogens
Will there be any hormone increases do to a 17-alphahydroxylase deficiency?
increases in 11-deosycorticosterone (weak mineralocorticoid) and increase in corticoserone (weak glucocorticoid)
but clinically it is only an increasein the weak mineralocorticoid.
What are the bodily effects of 17-alphahydrogenase deficiency?
increased blood pressure do to the increased weak mineralocorticoid.
Why does the secretion of aldosterone change in the 17-alpha hydroxylase deficiency/
the increased hypertension will shut down renin from kidney which will shut down angiotensin II which will shut down the zona glomerulosa.
How will the 17- alphahydrogenase deficiency affect the testes and ovaries?
It will shut down both testosterone and estrogen production.
What are the four stress hormones?
Growth hormone, glucagon, cortisol, and epinephrine
What is the function of growth hormone?
mobilizes fatty acids by invreasing lipolysis in adipose tissue
What is the function of glucagon
mobilizes glucose by increasing liver glycogenolysis
What is the function of cortisol
mobilizes fat, protein and carbohydrate
What is the function of epinephrine
mobilizes glucose via glycogenolysis and fat via lipolysis
which stress hormones are released in all types of stress?
growth homone and glucagon
when is cortisol not released?
when is epinephrine increased?
What is a hormone that decreases during stress and what is the function of that hormone?
Insulin tends to decrease in stress because it mainly promotes the storage of the products of digestion.
Cortisol promotes the mobilization of what energy stores specifically.
proteins, lipids, and carbohydrates
how does cortisol raise blood glucose
inhibits the periferal uptake of glucose
and not as importantly increases hepatic output of glucose via GLUCONEOGENESIS from amino acids in particular (NOT FROM LIVER GLYCOGENOLYSIS)
What are the permissive actions of cortisol?
It works with glucagon in the liver to promote glycogenolysis. with out cortisol, fasting hypoglycemia rapidly develops.

It also works with catacholamines to promote glycogenolysis and lipolysis in liver and muscle. It promotes vasoconstriction and bronchodilation. WITHOUT CORTISOL BLOOD PRESSURE DECREASES.
What controls the release of CRH from the hypothalamus and thus the release of cortisol.
Stress and Circadian Rhythm
When does the circadian rhythm input to release CRH peak and when is it lowest.
The circadian rhythm input for the release of CRH from the hypothalamus is highest in the morning and lowest in the evening.
What is the prohormone for ACTH?
What does the prohormone pro-opiomelanocortin break into and why is each of these parts important.
pro-opiomelanocortin breaks into ACTH and Beta-lipotropin which is important because this molecule is breaken down to form Beta-Melanocyte Stimulating Hormone and endorphins.
Why are Beta MSH and ACTH important?
Beta-MSH and ACTH are important because they can cause darkening of the skin.
What is one disorder where you will find darking of the skin due to ACTH and beta-MSH?
primary adrenal insufficiency.
What is usually the cause of primary hypercortisolism
tumor secreting excessive amount of cortisol
What is primary cause of secondary hypercortisolism
tumor in the pituitary gland increasing secretion of ACTH.
What is the primary cause of primary hypocortisolism and what is another name of this?
The primary cause the primary adrenal insufficiency and primary hypocortisolism is seen in Addison's disease.
What is the cause of secondary hypocortisolism?
Lack of secretion of ACTH from the pituitary gland.
What is another name for hypercortisolism?
cushing syndrome
What is the most important action of aldosterone?
most important action is to increase Na+ reabsorption by the collecting ducts
What does aldosterone do to the conc. of sodium in the ECF?
aldosterone does not change conc. it in creases the total amount.
what do the juxtaglomerular cells monitor and what are they innervated by?
they monitor the blood pressure in the kidney and are innervated by sympathetic neurons
What are the macula densa cells and that is their function.
These are cells that line the distal tubule and come into contact with the juxtaglomerular cells. They monitor the sodium chloride in the distal tubule.
What is your short term and long term control of blood pressure.
The short term regulation is the carotid sinus reflex and the long ter mregulation is the renin-angiotensin-aldosterone system.

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