W3006 Physiology Fall 1999 Problem set #3: Central endocrine, Lactation

1. Where in the cells of the anterior pituitary gland would you expect to find hormone receptors?

a. on the plasma membrane b. in the nucleus c. both a. and b.

2. For each of the glands listed below, indicate whether it releases hormones in response to a. nervous stimulation

b. hormonal stimulation c. a change in concentration of a chemical in its surroundings (Give more than one answer if appropriate)

A. Follicle cells of thyroid B. Hypothalamus C. Posterior pituitary D. Anterior pituitary E. Adrenal cortex

F. Parathyroid gland

3. Use the following key to answer these questions (Use more than one answer if appropriate.)

a. adrenal medulla e. anterior pituitary

b. adrenal cortex f. posterior pituitary

c. hypothalamus g. None of these

d. follicle cells of thyroid

_______1. Hormones produced here are released into the blood stream through a duct.

_______2. This is derived from nervous tissue in the developing embryo.

_______3. This is made mostly of connective tissue.

_______4. Hormones produced here combine with intracellular receptors in their target cells.

_______5. An otherwise healthy 3-year old boy was examined because he ate huge amounts of salt daily. Doctors tried to cure him of this habit by putting him on a salt-free diet. Two days later, he died. Autopsy showed he lacked a normal_______.

_______6. Hormones produced here are modified amino acids.

_______7. This gland receives hormones through a portal vessel.

4. Which of the following is/are neuroendocrine secretion(s)? a. cortisol b. TRH c. TSH d. thyroxine e. vasopressin
5. The anterior pituitary gland releases gonadotropins, hormones that stimulate the gonads (ovaries) to both secrete ovarian hormone (estrogen and progesterone) and to release an egg. Gonadotropin secretion is controlled in a manner similar to ACTH secretion. Some women are infertile because they produce insufficient gonadotropins. They can be treated by injection of a substance isolated from the blood or urine of elderly Italian nuns. These women are post-menopausal, meaning that their ovaries are no longer producing hormone.

A. What substance would you expect is in their blood in such high levels? B. Why is it high in these women?

6. A scientist wants to know how prolactin is controlled. In one group of rats (the control), she measures prolactin in the blood. From rats in a second group, she removes the prolactin secreting gland from its usual location and transplants it to the surface of the kidney, where it soon develops connections with the existing blood vessels. She measures prolactin in the blood, and finds that it is much higher than in the control animals. What does this imply regarding the usual control of prolactin secretion in rats?
7. After childbirth, the placenta detaches from the uterus and for the next couple of weeks, the uterus bleeds much as it does during a menstrual period. The uterus, which has enlarged to be big enough to hold a fetus, shrinks back to the size of a fist. This process can be accelerated and less bleeding will occur if the mother breastfeeds her baby. Explain how breastfeeding can have an affect on the uterus. Include the hormone(s) involved and the control pathway.
8. For each of the following, explain whether it is true SOMETIMES, ALWAYS, or NEVER. Explain your answers.

A. If the hypothalamus were destroyed, secretion of all anterior pituitary hormones would cease.

B. Injecting oxytocin into a human causes milk ejection.

C. Hormones combine with specific receptors on the cell membrane of the target cell.

D. The integrator in homeostatic control systems is located in the hypothalamus.

9. Studies were conducted in rats before and after parturition (giving birth). The following changes were measured during the postpartum period when compared to the pre-partum period: a)mRNA coding for oxytocin was ten times higher in the PVN (paraventricular nucleus of the hypothalamus) postpartum than prepartum, and b)oxytocin content of the posterior pituitary gland was half as much postpartum than prepartum.

A. Why did the scientists choose to measure oxytocin mRNA in the hypothalamus rather than in the pituitary gland?

B. Suggest a reason why oxytocin content of the posterior pituitary gland declined postpartum.

Further studies indicated that some oxytocin-containing cells of the hypothalamus project to other brain areas rather than to the pituitary gland. The experimenters suggested that in addition to the well-known physiological effects of oxytocin, this hormone also influences behavior. They decided to study the effects of oxytocin on maternal behavior.

C. Why did they choose to study specifically this behavior? In your answer, include the known physiological effects of oxytocin.

D. OTA is a compound that binds tightly to the oxytocin receptor. If OTA is made radioactive, and added to slices of brain, the presence of radioactivity is indicative of the presence of oxytocin receptors. (This technique is called receptor autoradiography.) You have two species of very closely related rodents, prairie voles and montane voles. Prairie voles show a lot of maternal behavior, whether or not they've given birth. Montane voles show no maternal behavior till after they've given birth. Design an experiment using receptor autoradiography and these two species to further study whether oxytocin plays a role in maternal behavior. Your answer should include the experiment you would do, the possible results you might get, and which of these results would support the hypothesis that oxytocin plays a role in maternal behavior.

10. A woman who broke her leg needed to use crutches for walking. After using them for several months, she began to lactate, apparently due to pressure put on a nerve while she leaned on the crutches. Describe the neuronal and/or hormonal pathway that is responsible for lactation under normal circumstances. Then explain how the pressure from the crutch triggered this pathway.

(Note: These are the old-fashioned crutches that rest in the underarm area, not the new-fangled metal ones that cover just the lower arm.)

11. Explain what is meant by a non-tropic hormone, and name one hormone from the anterior pituitary gland which fits that definition.
12. During larval development of a toad, skin cells grow inward to form a gland. When thyroid hormone is present, this gland develops more rapidly. When corticosterone is present, the gland doesn't develop at all. (Corticosterone is produced by animals instead of cortisol, but control of its secretion is similar to that of cortisol.) Corticosterone might inhibit gland development by acting either

1. on the skin cells, to cause (up-regulation) (down-regulation) of the receptors for (corticosterone) (thyroid hormone) OR
2. on the anterior pituitary gland, to (stimulate) (inhibit) its secretion of (TRH) (TSH) (Thyroid Hormone) (ACTH) (CRH) (corticosterone).

1. A person is in an accident that destroys the entire pituitary gland without harming the rest of the body. In the absence of stress, this condition is not fatal, but some aspects of homeostasis will be disrupted.

A. For each of the following hormones, indicate whether its secretion should increase, decrease, or not change after the accident:

ACTH ADH Cortisol Estrogen

CRH GnRH Gonadotropins (LH/FSH) Growth hormone Insulin Oxytocin Prolactin Testosterone

Thyroid hormone TRH TSH PTH

B. The lack of TWO of the PITUITARY hormones will disrupt homeostasis. Which two hormones are these? Explain how the lack of these hormones leads to impairment of homeostasis.

C. These defects are usually remedied by replacing the missing hormone. But for ONE of the defects in homeostasis, a behavioral change in dietary intake is often sufficient to restore homeostasis. The person just has to take in (more than) (less than) the usual amount of _________________. Explain how this eliminates the problem.

2. Heroin causes a sudden increase in release of proteins from liver to blood. Soon after using heroin, levels of free (unbound) thyroid hormone decrease, but soon return to normal.

A. Why does free thyroid hormone decrease?

B. Why is this decrease temporary?

C. Free thyroid hormone returns to normal. You would expect to find total thyroid hormone (that is, bound + free) to be higher/lower/the same as normal. Explain.

3. Consider the pathway involved in regulating milk-let down.

A. Does this pathway use negative or positive feedback?

B. What is the receptor?

C. What is the integrator?

D. What is the effector?

4. Which is greater? x, y, or both equal?

A. x. the distance travelled by an autocrine signal to reach its receptor

y. the distance travelled by an exocrine signal to reach its receptor

B. x. length of hypothalamic neuroendocrine cells that release ADH

y. length of hypothalamic neuroendocrine cells that release ACTH

D. x. distance travelled by a neuroendocrine secretion to reach its target receptor

y. distance travelled by a paracrine secretion to reach its target receptor

E. x. water-solubility of oxytocin

y. water-solubility of estrogen

5. Dr. Humbug has noticed that oxytocin and prostaglandins are about equally effective in inducing labor in women near term (that is, at the end of nine months of pregnancy). However, oxytocin is much less effective than prostaglandins in inducing abortion during the first trimester of pregnancy. Explain why.
6. T/F Steroid hormones are released from endocrine cells by exocytosis.
7. T/F All hormones are synthesized first as pre-prohormones.
8. T/F The target cells of prolactin are derived from epithelial tissue.

1. c These cells have membrane receptors for peptide hormones from the hypothalamus, as well as intracellular receptors for steroid hormones, which affect the pituitary by negative feedback.
2. A. b (TSH) B. a (receives input from other brain areas. Infant sucking nipple stimulates neuronal pathway that stimulates the release of hypothalamic factors that control prolactin release.) b (The hypothalamus is sensitive to negative feedback from some of the hormones produced by target organs.) c (The hypothalamus is also sensitive to the concentration of certain chemicals in the blood - receptors measure glucose levels, and signal release of the releasing hormone that stimulates the anterior pituitary gland to release ACTH.) C a (Neuronal impulses from infant sucking at nipple causes release of oxytocin.) c (Concentration of solutes in blood is measured by osmoreceptors, which regulate ADH release.) D. a (controlled by releasing hormones and inhibiting hormones from the hypothalamus) E. b (ACTH from anterior pituitary regulates cortisol release) c (aldosterone, which controls salt content of body, is secreted in response to salt concentration of blood)
3. 1)g 2)a c f 3) g 4) b d 5) b (no aldosterone. This happened in the 1930's, and was the case that led doctors to first understand the role of the adrenal cortex.) 6) a d 7) e
4. b e
5. A. Gonadotropins. B. As with ACTH, control is as follows: Hypo ---> GnRH ---> Ant pit ---> Gonadotropin ---> ovary ---> Estrogen + Progesterone. Since the post-menopausal women don't produce E/P, there is less negative feedback on the anterior pituitary gland and/or hypothalamus, and so more gonadotropins will be secreted into the blood. (There will also be more GnRH in the portal vessel, but this is so diluted by the time it reaches the general circulation that it will not be found in significant levels in the urine.)
6. Prolactin secretion must usually be under inhibitory control, probably by a hypothalamic inhibitory hormone, since it is produced by the anterior pituitary gland, which receives blood from the hypothalamus by way of a portal vessel. Removing the anterior pituitary from this portal vessel results in increased prolactin secretion, suggesting that secretion is usually inhibited by something from the hypothalamus. The prolactin-inhibiting hormone would be so diluted in the general circulation by the time it reaches the kidney, and so wouldn't affect the transplanted pituitary gland.
7. A sucking infant stimulates a neuron near the nipple, which conveys nerve impulses to oxytocin-containing cells in the posterior pituitary gland. These cells are stimulated to release oxytocin. There are receptors for oxytocin in the myoepithelial cells of the breast (where it stimulates milk let-down) and in the uterus (where it stimulates muscle contraction). The contracting uterine muscles clamp down on the blood vessels, so less bleeding occurs.
8. A. sometimes. Certain hormones wouldn't be secreted, if they depend on a releasing hormone for their release. But others (prolactin) are secreted constitutively and control is generally through an hypothalamic inhibiting hormone - Remove the inhibition and secretion increases. B. Sometimes. Oxytocin stimulates contraction of myoepithelial cells. Milk will be ejected only if PRL has been present to stimulate its synthesis. C. Sometimes. Peptide hormones do, but steroid hormones combine with intracellular receptors. D. Sometimes. For temperature regulation, the hypothalamus is the integrator, but for regulation of calcium levels, the hypothalamus is not involved; the parathyroid gland is the integrator.
9. A. Oxytocin is secreted from the posterior pituitary gland, but synthesized in the hypothalamus, so you'd expect to find mRNA in the hypothalamus. B. The posterior pituitary gland stores oxytocin in vesicles prior to release. At parturition, oxytocin is released to stimulate uterine contraction and milk let-down, depleting stores of oxytocin. C. Oxytocin stimulates contraction of uterine smooth muscles, expelling fetus and stimulates contraction of myoepithelial cells around mammary glands, allowing milk let-down. Since maternal behavior is the behavior that occurs at the same time as these physiological changes, it's logical to think that oxytocin is the hormone that stimulates this behavior. D. Use receptor autoradiography to measure the amount of oxytocin receptors before and after the animals give birth, and compare the results when this is done in each of the two species. Possible results: a. prairies: oxy receptors high before and after, montanes: oxy receptors low before and after. This would support the hypothesis that oxytocin is related to maternal behavior. b. . prairies: oxy receptors low before, high after, montanes: oxy receptors low before, high after. This would indicate that receptors increase in relation to parturition, but wouldn't support the hypothesis that oxy is involved in maternal behavior, since prairies show behavior before parturition, when receptors are low. c.. prairies: oxy receptors high before, low after, montanes: oxy receptors low before and high after. This would indicate that receptors are related to some difference between the species, but would not support the hypothesis that oxytocin is involved in behavior, because montanes show such behavior after, even though receptors are low.
10. See pathway described in class/textbook. The neuron from the breast that is usually stimulated by infant sucking passes under the arm towards the spinal cord, where it synapses on neurons leading to the hypothalamus. There it stimulates hypothalamic neurons secreting PRF (and inhibits those secreting PIF) so that prolactin is secreted from the anterior pituitary gland, and it also stimulates hypothalamic cells synthesizing oxytocin, so that oxytocin is released from the posterior pituitary gland, stimulating milk ejection. The crutches put pressure on this neuron, stimulating it along the axon, and sending similar messages back to the hypothalamus. NOTE: A single case study like this was published in a medical journal because it was so unusual. External pressure from crutches is usually not enough to cause lactation! You may be surprised that lactation can occur in women who haven't been pregnant, but it turns out that much stimulation of the neuron can do this. A woman who adopts a baby sometimes want the experience of nursing the infant, and if she stimulates her nipples frequently (several times a day, for about a month) she may be able to induce lactation.

11. Tropic hormones are those that act on other endocrine glands, causing them to grow and secrete hormones. Non-tropic hormones act on non-endocrine tissues. Example: Prolactin, which acts on epithelial cells of mammary glands.
12. A. down-regulation of receptors for Thyroid Hormone OR B. inhibit secretion of Thyroid Stimulating Hormone

In case A, TH would still be produced, but cort would prevent the cells from responding because it decreases the number of receptors for TH (down-regulation). In case B, receptors would still be present, but cort would be preventing the cells from seeing the TH in the first place, by preventing it from getting into the blood. In question B, the other choices given either are not secreted by the anterior pituitary gland (TRH, TH, CRH, cort) or don't affect the production of TH needed for the gland development (ACTH).

13. A. Hormones secreted from the pituitary will decrease (ACTH, oxy, ADH, prl, TSH, Gn, GH). Hormones that are normally found in the blood as a result of pituitary gland hormone stimulation of target glands will also decrease (cort, T, E, TH) . Hypothalamic hormones whose secretion is subject to negative feedback from hormones that are under pituitary control, will increase (CRH, TRH, GnRH). Hormones not affected by pituitary gland will not change (Insulin and PTH).

B. ADH and TSH. ADH stimulates kidney to reabsorb water, so without it the body becomes dehydrated, unable to maintain blood pressure within normal limits. TSH stimulates the thyroid to produce TH to maintain metabolic rate, temperature, oxygen consumption, so the body will have trouble maintaining these. (Note: you may have answered "ACTH", but a lack of ACTH is not a problem unless the body is under stress, in which case the lack of cortisol may cause blood glucose levels to fall. But the question specifies that there's no stress.)

C. Drink more than the usual amount of water. This will clear up the dehydration problem even if ADH is not administered. Explanation of less good answers: Eating more salt will increase water retention, but the body will have more salt as well, or a high osmolarity, implying that the organism is still dehydrated. Eating less salt will decrease some of the need for water, but you can't cut salt intake enough to compensate for the enormous water loss. Increasing iodine intake will increase TH production, but only if TSH is present will the thyroglobulin be cleaved to release the TH for secretion. Increasing glucose intake would restore blood glucose in stress, but this isn't a major problem, since epinephrine would also be present and does the same thing.

14. A. TH (T3 and T4) is lipophilic, so is transported through the blood in association with blood proteins. This association is reversible, and there's always a certain percentage of hormone that's bound and that's not bound. Blood proteins are produced by the liver, and the increase in these proteins would cause more TH to be bound up, so decrease the level of free TH.

B. The free TH can diffuse into cells, and it diffuses into cells of the hypothalamus and anterior pituitary gland, where it exerts negative feedback effects. With more TH bound, there's less free TH, so less negative feedback, so TSH secretion will start to increase, which causes TH secretion to increase, and so restores free TH in blood to previous levels.

C. Higher. Same amount is free, but more is bound.

15. A. positive B. touch receptors around nipples C. hypothalamus D. myoepithelial cells around mammary glands
16. A. y B. x C. x D. x E. x F. y
17. For oxytocin to cause muscle contraction, it must first combine with receptors. At the end of pregnancy, there are many of these, but early in pregnancy there are fewer oxytocin receptors.
18. F (diffuse through membrane)
19. F (only peptide hormones)
20. T (mammary glands are exocrine glands, a type of epithelial tissue)