Hormones

Fox Chapter 11, part of chapters 2, 9, 19, 20

Introduction

Metazoans (animals with more cells than protozoans) require systems of integration
INTEGRATION: Hormones, paracrine (local) & nervous system
"endocrine" - ductless, into blood stream
vs. exocrine (like digestive - saliva etc.)

Three steps:
cells with blood vessels for release
hormone transported in the circulation
target cell with receptor

Two mechanisms
(1) receptor molecule on membrane
(2) enter cell and bind receptor

Overview

TRANSPARENCY (From intro bio)

Fig. 11.1
I. Traditionally, this material starts with a picture of the major glands

II. Then it covers Pituitary three ways
(1) posterior pituitary
(2) anterior pituitary as "master gland" (and the other glands it controls)
(3) anterior pituitary (affects not mediated through other glands)

III. Then it covers other glands (not controlled by the pituitary)

Based on feedback from the 2011 assessment, IV and V are covered in separate lecture outlines

IV. I will then give you a dose of "signal transduction" concentrating on steroids, thyroid and retinoic acid.

V. I will cover sex hormones in detail last (after glossing over them under II.(3) [above])

A later lecture outline, Reproduction, will take off beyond III. and V.

Posterior pituitary

TRANSPARENCY

Fig. 11.13
(related to kidney coverage)
neurosecretion from hypothalamus (peptides)
"suprachiasmatic" means over the optic chiasm
"paraventricular" means near the (third) ventricle
oxytocin (milk, delivery)
(synthetic to induce labor)
Covered in Excretion lecture: ADH action on kidney
vasopressin (ADH), H2O and blood pressure
alcohol, caffein inhibit anti [diuresis] hormone

Anterior pituitary

TRANSPARENCY

Fig. 11.15
Median eminence from hypothalamus to pituitary
Secretion of releasing (and inhibiting) hormones (peptides) at pituitary stalk
Portal system
Anterior pituitary and its hormones (peptides)

Fig. 11.14
(on right of figure) Master gland to show glands controlled by pituitary (thyroid, adrenals, ovary, testes) Trophic (tropins like "gonadotropins")
(on left of figure) not using other endocrine glands (Growth hormone and Prolactin)

Non-trophic hormones
(not where pituitary acts as master gland to control other glands)

GH - 200 a.a. -bone, muscle, not fat, -> liver to make somatomedins
GH - gigantism (bones grow long if too much GH when young), dwarfism (if too little GH when young), acromegaly (bones grow too thick if too much GH when already grown up, danger of GH abuse), abuse by body builders, dangers of extracts,, now available through recombinant DNA research

Prolactin - milk production, like GH (same ancestral gene)

Trophic hormones
(like gonadotropins) "Master Gland"
sex hormones from pituitary (more details later):
LH (female) = ICSH (male); (luteinizing) (interstitial cell)
FSH (follicle)
non-sex trophic hormones from pituitary:
TSH (thyroid)
ACTH (adrenal cortex)

TRANSPARENCY (again or still)
Review - same material, intro course

Thyroid hormones

(recall that thyroid was used as hormone example in first lecture outline)
Influence on metabolism, but not as obviously as epinephrine, insulin, glucagon or even glucocorticoids.

Fig. 11.25
Negative feedback with pituitary
Hypothalamus -TRF-> + Ant. Pituit. -TSH->+ Thyroid -> thyroxine-
- neck thyroxin (T4), triiodothyroxine (T3) iodine, sea food (and iodized salt)

Fig. 11.3 (also shown in an earlier lecture)
T3 and T4

Figs 11.24, 11.26
Goiter (thyroid overgrows if too little iodine in diet)
Cretinism if too little in infant, hypothyroid, hyperthyroid
Change in salmon during salt to fresh water change, metamorphosis in frog
Problem of radioactive iodine (like from reactor leaks) - helps to take large doses of non-radioactive iodine to compete

Adrenal gland

Fig. 11.20
Adrenal cortex - Glucocorticoids stimulate metabolism, inhibits inflamation.
JFKennedy had too little glucocorticoids (needed replacement therapy) which would create a situation of no feedback - too much ACTH (darkens skin like MSH).
pro-opiomelanocortin - big peptide cleaved to ACTH, MSH, endorphins, enkephalins
Emphasize regulation, negative feedback

Fig. 11.18
Zona glomerulosa - mineralocorticoids
Zona fasciculata and reticularis - glucocorticoids and androgens
Mineralocorticoids, the best known being Aldosterone helps kidney retain salt
Adrenalectomy causes salt loss and salt appetite.
Sweat glands are not as efficient at retaining salt as kidney.
That is why "Gatorade" (electrolyte) is used by athletes.
Salt is also lost in cystic fibrosis (mutation of CFTR (cystic fibrosis transmembrane conductance regulator)

Female reproductive cycle

good example of Regulation, Negative feedback
CHAULKBOARD DIAGRAM
Hypothalamus - RF's (peptides)
(chaulkboard diagram is also here, peptides in black, steroids in red)
Pituitary makes peptide hormones "gonado-trophic hormones" (gonadotropins, FSH and LH)
gonads (ovaries) make steroid hormones (estrogen and progesterone)
Feedback system plus effects on endometrium (lining of uterus)

FSH (follicle stimulating hormone) stimulates estrogen release from follicle
estrogen inhibits FSH
estrogen turns on LH (lutenizing hormone) release
estrogen begins buildup of endometrium
surge of LH causes ovulation
then follicle becomes corpus luteum that puts out progesterone
progesterone inhibits LH and FSH
progesterone also stimulates buildup of endometrium
to finish cycle, low FSH & LH which lets estrogen and progesterone go down
(corpus luteum starts to go away)
with low estrogen and progesterone, endometrium breaks down (menstruation)
with low estrogen and progesterone, pituitary is not inhibited so FSH starts
(if pregnant, HCG [human corionic gonadotropin] maintains corpus luteum
progesterone (from maintained corpus luteum) maintains endometrium
Here is a primary follicle, a growing follicle, the mature follicle, and the corpus luteum from our histology course.

Human corionic gonadotropin
Menstruation in primates
Estrus cycle - dogs heat 2x/yr, cats 3x/yr
Rabbits reflex ovulators
Pill Progesterone and Estrogen inhibit ovulation
28 day pill 7 duds: 1st 4 days, last 3
"combination pill"
Weight gain, circulation problems
lower proportion of estrogen
Rhythm - sperm viable 48 hr, ovum 15 hr: 3-4 day abstinance

The male pattern
FSH for spermatogenesis
LH (ICSH) to stimulate interstitial cells to release testosterone

Glands not controlled by pituitary

Adrenal medulla


Fig. 9.8
while on the topic of the adrenal gland,
Adrenal medulla (vs cortex under pituitary control)- Epinephrine, (alias adrenalin) - activates body
Autonomic (vs voluntary) motor control: sympathetic (vs parasympathetic)
Sympathetic nervous system uses norepinephrine at postganglionic synapses.
Sympathetic - "fight or flight"
Helps in metabolism to release glucose to blood stream
Muscles activity up, peripheral circulation and digestion inhibited
Heart rate goes up

Glucose (insulin and Glucagon) and diabetes
was moved from here to earlier

Calcium homeostasis

TRANSPARENCY (From introductory book)
Thyroid 2 glands (pituit - thyroxine TSH) vs:
Thyroid - thyrocalcitonin - blood Ca2+ down
Parathyroid - parathormone - blood Ca2+ up (from bones)
near thyroid gland in neck
Vitamin D sunlight, rickets, fish oil, hormone, absorption from gut
Osteoporosis - bone deterioration with age especially in women
Ca2+ very important, muscle (later), nerve (later)

Fig. 11.28
review, parathyroid hormone

Fig. 19.18b
PTH increases blood Ca2+
Osteoclast uses enzymes and acid to dissolve bone CaPO4

When calcium is needed a lot, bone depleted.
Osteoporosis, more common in women because of Ca2+ use in lactation.

Fig. 19.22
PTH effect on bone shown again here plus:
In kidneys, Ca2+ reabsorption is increased
and
In kidneys, 1,25-Dihydroxyvitamin D3 is made
(and that, in turn, increases intestinal absorption)

Working the vitamin D topic backward:

Fig 19.19

Fig. 19.21
kidney enzyme (1-alpha-hydroxylase) acts on 25-hyrdoxyvitamin D (from liver)

and

Fig. 19.21
Vitamin D from sunlight in skin
(plus liver and kidney shown in this figure)

Fig. 19.23
Calcitonin from the thyroid does the opposite


Exam questions from 2004 - 2011 relevant to this outline

Why would we refer to oxytocin as a "neurosecretion" but not ACTH?

oxytocin comes from nerve cells of the hypothalamus, ACTH from endocrine cells of the anterior pituitary

Answer one of the following: Releasing hormones are produced by (what structure?) and have their effect on (what structure?) after being carried by (what conduit?).

hypothalamus, anterior pituitary, portal vessel

Under the influence of growth hormone, bones get longer while you are growing. How does growth hormone affect bones after you are full grown?

acromegaly, they get thicker

Glucocorticoids - answer either - (1) are produced where? (be specific) or (2) feed back to the anterior pituitary to inhibit the release of (what hormone?).

adrenal cortex (ok if you wrote zona fasciculata and reticularis), ACTH

Steroids of the ovary are secreted by what specific portion(s) of the ovary?

follicle, corpus luteum

Fertility is blocked by the pill...answer one of these: (1) How is fertility blocked? or (2) Why would there still be menstruation every month?

no ovulation (b/c no LH or FSH [b/c of steroids in the pill]), steroids build up endometrium, then lack of steroids let it break down

Why would a couple only need to abstain from intercourse for a few days per month to avoid pregnancy?

egg only present and viability are limited as is the viability of sperm delivered near the time when the egg is present up in the uterine tube

Something the size of the fertilized egg, but further developed, implants into the receptive endometrium. A portion develops into an endocrine-secreting tissue. Answer either (1) What is the function of the hormone it produces? or (2) What is the chemical nature of the hormone it produces?

maintain the corpus luteum, peptide

Vitamin D has effects more similar to (which?) calcitonin or parathormone. Explain (justify).

increase blood calcium like parathormone

An osteoclast contributes to the regulation of blood calcium ... Answer either (1) under the influence of what hormone? (2) how?

parathormone, secrete HCl to break down calcium phosphate and enzyme to break down collagen

The synthesis of 1,25-Dihydroxyvitamin D3 from 7-Dehydrocholesterol involves kidney, liver, and (what other organ?).

skin

With respect to its effects in the breast and in the uterus, what type of cell is affected by oxytocin?

smooth muscle

If iodine is adequate, thyroid hormones (T3 and T4) feed back to the anterior pituitary to inhibit the release of (what hormone?).

TSH

A surge of LH leads to what changes in the ovary? (There are two answers but you need provide only one.)

ovulation, conversion of the follicle to the corpus luteum

There is a new hormone after implantation, and it is a good one to assay to test for pregnancy. What is that hormone?

HCG

Calcium-regulating hormones regulate blood levels of calcium ions at three sites, bone, intestine, and (where else?).

kidney

The kidney and the liver are two of the three organs used to make 1,25-Dihydrovitamin D3. What is the third organ?
 
skin
 
A gland in the neck puts out a hormone that inhibits the dissolution of CaPO4 from bone. Name EITHER (1) the gland or (2) the hormone.
 
Thyroid, calcitonin
 
What are the gonadotropins for spermatogenesis and testosterone secretion?
 
FSH and LH (ICSH)
 
Why is an enzyme (as well as acid) a useful secretion of an osteoclast?
 
Digest the collagen that the calcium phosphate was embedded in
 
In its effects in the mammary gland and uterus, what kind of cell is affected by oxytocin?

smooth muscle

If a body builder abuses growth hormone, what is likely to happen to his or her bones?

they will grow in thickness

What is a general term that takes into account the trophic influence for both males and females of FSH, LH, ICSH and HCG?

gonadotropin

What happens if there is too little thyroid hormone during an infant's development?

brain development is compromised (cretinism)

"The follicle includes a 'rind' of cells and the egg enclosed in this rind." What does this rind do?

secretes estrogen

"There is a surge of LH." Answer one (1) Where did this LH come from? (2) What kind of molecule is that LH? Or (3) Name one of the effects that has on the ovary.

pituitary, peptide, convert flooicle to corpus luteum, cause ovulation

Would the endometrium build up and break down in women who are taking the pill? (Include in your answer why or why not.)

yes, steroids would cause build up and duds (without steroids) would allow break down

What happens to the corpus luteum after implantation?

It is maintained and continues to secrete progesterone under the influence of HCG

What kind of molecules, biochemically, are the hormones released by the posterior pituitary?
 
peptides
 
One capillary net is in the infundibulum and receives its hormones as neurosecretions from the paraventricular and preoptic areas of the hypothalamus. Obviously, I am describing a portal system. Where is the second capillary net?
 
Anterior pituitary
 
Why did former President Kennedy seem to have a nice sun tan?
 
With low cortisol from Addisons disease, little feedback resulted in too much ACTH which overlaps with MSH (melanocyte SH)
 
Would the corpus luteum build up and break down in women who are taking the pill? (Include in your answer why or why not.)
 
no b/c steroids of the pill inhibit FSH and LH which would build follicle into corpus luteum
 
A gland in the neck puts out a hormone that causes the dissolution of CaPO4 from bone to increase blood calcium. Name EITHER (1) the gland, (2) the hormone, or (3) the cell that mediates dissolution of the bone.
 
Parathyroid, parathyroid hormone, osteoclast
 
What is the hormone from the adrenal medulla?
 
Epinephrine (adrenalin)
 
What is the function of a signal known as "inhibin?"
 
feedback on FSHs effectiveness on seminiferous tubules
 
Loss of what hormone would cause an adrenalectomized animal to crave salt?

aldosterone

What is the name of the disorder of too much growth hormone as an adult?

acromegaly

Vitamin D helps to keep the blood levels of what substance correct?

Ca2+

Historically, shortage of what mineral caused some inland people to develop goiter?

iodine

Why are alcoholic beverages contraindicated to stay hydrated in times of heat stress? (Make sure your answer says what happens to the relevant hormone level.)

alcohol inhibits ADH, more water is lost through kidney

After ovulation, the estrogen secreting follicle turns into a tissue that secretes what hormone?

progesterone

In the process where epinephrine causes glucose release from liver, what enzyme does cAMP activate?

protein kinase A

What kind of chemical is a gonadotropin?

peptide

The birth control pill feeds back to inhibit what pituitary peptide (to prevent maturation of the follicle)?

FSH

What does the osteoclast do to assist in Ca2+ homeostasis?

cause bone to release Ca2+

What pituitary hormone maintains the cells that secrete testosterone?

LH

Within the ovary, what tissue produces estrogen?

follicle

Why is the term "anabolic" applied to some hormones?

growth (muscles, bone, hemoglobin)

Where are the cell bodies of the cells whose axon terminals release ADH and oxytocin?

hypothalamus

ACTH triggers the release of what hormone from its target gland?

cortisol

What is the tissue responsible for producing the gonadotropin that supports the corpus luteum early in pregnancy?

chorion

Why is such a small amount of thyrotropin-releasing hormone TRH needed?

because portal system delivers straight to anterior pituitary

Although dopamine is a transmitter itself, it can be converted into what other neurotransmitter by the enzyme dopamine beta-hydroxylase?

norepinephrine

What hormone would put calcium back into bones?

calcitonin

A surge of what peptide leads to ovulation?

LH

What second messenger activates protein kinase when the beta-adrenergic receptor of a liver cell binds epinephrine?

cAMP

What would happen to the TSH level if dietary iodine were deficient?

go up since negative feedback from thyroxine is decreased

What cleavage product of pro-opiomelanocortin would be high in Addison's disease?

ACTH

How would calcitonin regulate Ca2+ at the level of the kidney?

decrease resorption

In the term "gonadotropin," what does the suffix "tropin" refer to?

has trophic effect

What would happen instead of increase in bone length if growth hormone were too high in the adult?

bones would get thicker

In the old days, what would cod liver oil be used for?

vitamin D (and A) replacement

In the pathway 7-dehydrocholesterol -> vitamin D3 -> 25-hydroxyvitamin D3 ->1,25-dihydroxyvitamin D3, where does the first conversion take place?

in the skin

Osteoclasts contribute to the breakdown of CaPO4 plus what additional component, a protein, in bone?

collagen

A surge of LH mediates ovulation plus the conversion of the follicle into what tissue?

corpus luteum

What is it called when, because of low progesterone, the endometrium is no longer supported?

menstruation

What hormone supports the endometrium during pregnancy?

progesterone

What effect does calcitonin have on the kidney?

Allows for CaPO4 loss in urine

What type of chemical is the product of the Leydig (interstitial) cells?

steroid

Chemically, what type of molecule is a gonadotropin?

peptide

What would be the most common reason to administer oxytocin (or a synthetic version of this hormone)?

induce labor

Why would very small amounts of TRH be needed for adequate homeostatic control?

portal vessel from hypothalamus to pituitary means that it is not diluted by the systemic circulation

Although steroids in the birth control pill would have a trophic effect, building up the endometrium, they block pregnancy. By what mechanism?

by inhibiting FSH and LH, they prevent ovulation

What is the effect of the hormone of the adrenal medulla on heart rate?

adrenalin increases heart rate, of course

A lot of hormone from the parathyroid gland would decrease calcium in what notable reservoir in the body?

bone

Ovulation, as well as the conversion of the follicle to the corpus luteum, is induced by a surge in what pituitary peptide?

LH

PTH, the hormone of the parathyroid, acts on the kidney to stimulate Ca2+ reabsorption and inhibit PO4- reabsorption. What other effect does PTH have on kidney to help to increase plasma Ca2+?

formation of 1,25-dihydroxyvitamin D3 (increase 1alpha-hydroxylase activity

Who would suffer from acromegaly?

adults with too much growth hormone

Why would your skin be dark if you had Addison's disease (inadequate cortisol, no feedback, too much ACTH)?

ACTH mimics melanocyte stimulating hormone

Chemically, what type of hormones are the hormones of the adrenal cortex?

steroids

If estrogen and progesterone maintain the endometrium, how come women taking the birth control pill still have menstruation?

estrogen and progesterone are not given for a few days

Why is the term "neurosecretion" used for some hormones and give one example.

neurons with axons release chemicals from their terminals near blood vessels, ADH, oxytocin, releasing hormones

What happens if there is too much growth hormone in the fully-grown adult?

bones grow in thickness, not length, acromegaly

What leads to hypertrophy of the thyroid gland (goiter)?

deficiency of iodine

Why do they need to build fish ladders beside tall dams?

salmon go up their native stream to spawn

What type of chemical is the hormone secreted by the follicle?

steroid

After implantation, what peptide stimulates the corpus luteum to continue progesterone secretion?

human chorionic gonadotropin

What important cell, other than the hormone-secreting cells, is present in the follicle?

the egg

What type of chemical is the hormone that has a trophic effect, causing the Leydig cells (interstitial cells) to release their hormone?

peptide

H2CO3 is split in osteoclasts. Where do the two portions go and why?

H+ for acidity into bone on one side of the osteoclast, HCO3- exchange with Cl- on the other side to start Cl- toward the bone to make HCl

Which hormone from a gland inside the neck has the same effect on plasma calcium ion concentration as 1,25-dihydroxyvitaminD3?

PTH

Why might you want to inhibit the normal function of osteoclasts?

to stave off osteoporosis

ACTH is cleaved from what peptide precursor?

proopiomelanocortin

What organ are the steroid-secreting zona fasciculate and zona reticularis part of?

adrenal cortex

Out of a long laundry list, tell me one precursor of the hormone from the adrenal medulla.

tyrosine, l-DOPA, dopamine, norepnephrine

What is it called when a hypothyroid condition as an infant leads to deficient neural development?

cretinism

What is the condition where there is too much ACTH? - Answer one: (1) name of condition (2) What is there too little of? Or (3) Why does the skin get dark?

Addison's disease, too little cortisol, ACTH is like MSH (melanocyte stimulating hormone)

The adrenal cortex is famous for producing androgens, glucocorticoids and (what else?).

mineralocorticoids (aldosterone)

Norepinephrine is converted to epinephrine to be the major hormone of what (specific) gland.

Adrenal medulla

Why would cod liver oil be a useful dietary supplement for some people?

Vitamin D

Address the terms "paraventricular" and "supraoptic" in ONE of the following ways: (1) What part of the brain are they in? (2) How did those nuclei get those names? (3) What structure is the output of this neurosecretion? Or (4) What are the hormones?

hypothalamus, around the (third) ventricle and above the optic chiasm, posterior pituitary, ADH or oxytocin

For one portal system, the first capillary bed is in the pituitary stalk. Answer ONE of these (1) Where are the cell bodies responsible for secretion into this vascular bed? Or (2) Where (specifically) is the second capillary bed?

hypothalamus, anterior pituitary

Distinguish between what happens with too much growth hormone as a child vs as an adult.

become a giant, acromegaly

How come women who took the birth control pill still menstruated?

out of the 28 days, the steroids are not in the last 5 days so the endometrium is not supported

What are the two different functions of the pituitary gonadotropins in the male?

FSH spermatogenesis, LH getting the interstitial cells of Leydig to secrete testosterone

A surge in LH converts the follicle to the corpus luteum and (what else does it achieve?).

causes ovulation

Why doesn't the endometrium break down once FSH and LH stop maintaining the corpus luteum when implantation has occurred?

HCG supports the corpus luteum, so there is still progesterone

Starting with 7-Dehydrocholesterol, what is the order of action of the 3 separate ORGANS in the production of the active form of vitamin D?

skin, liver, kidney

A hormone from the thyroid has (what effect on the kidney?) for calcium homeostasis.

calcitonin stimulates excretion of Ca2+

"If the mother plans to breast feed, it is useful to give her the baby to suckle right after delivery" for what endocrine reason?

to retract uterus

In what way would growth be different if there were too much growth hormone as a child vs. too much growth hormone as an adult?

bones get longer vs thicker

In addition to its negative feedback control on the hypothalamus/pituitary, what effect does estrogen have on the endometrium?

build up

"The pill"; one a day for 28 days: Why would women still menstruate?

estrogens - build up of endometrium, duds, let it break down

In addition to triggering ovulation, a surge of LH does what (to the endocrine structure/function of the ovary)?

follicle changes to corpus luteum

Once human chorionic gonadotropin "takes over," what is the status of FSH and LH release by the pituitary?

they are still not released, inhibited by progesterone

Once human chorionic gonadotropin "takes over," what is the status of FSH and LH release by the pituitary?

progesterone from the still functioning corpus luteum still inhibits Pituitary FSH and LH

In the old days, some people would have had rickets. What aspect of their life style (discounting diet) would have led them to have gotten this disorder while other people would not?

winter, clothing, sun avoidance

Zona facicularis and zona reticularis put out what hormone in addition to glucocorticoids?

androgens

What allows FSH to be released at the "beginning" of the cycle?

lack of inhibition because of lack of estrogen and progesterone

Why would osteoporosis become more of a potential problem after menopause?

lack of estrogen (which would have helped osteoblasts build bone calcium)

Several organs are involved in bioconversions of various molecules that have the words "vitamin D." What is the original precursor of all the vitamin D forms?

cholesterol

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