W3006    Fall 2003     Mini-exam #3         Physiology              Last 5 digits of CU ID #__________________________ 

1.  Mutations in the CYP19 gene, which codes for aromatase, were discovered in three XX infants.  The mutated gene does not produce a functioning aromatase.  A. In these infants, the following structures would be expected to have differentiated in which direction?   (10)   Answers in blue, Additional explanations in red

gonad  ____female_________       Mullerian ducts ____female_________     (fill-in with male or female)

The infant has normal XX chromosomes, so no SRY, and an ovary will develop.  If ovaries develop, then there's no MIH, which would cause Mullerian degeneration in males, and the Mullerian ducts can develop in the normal female direction, ie, oviduct and uterus.

B. The girls were born with a very enlarged clitoris and with fusion of the labioscrotal region, as would occur in congenital adrenal hyperplasia.  The doctors determined that these girls did not have CAH, because each girl had: Circle all correct answers and give a brief explanation.   (20)

The question is asking How could the doctors have eliminated the diagnosis of CAH. That is, which of these would indicate that CAH is not a possibility.  In CAH, the enzyme for synthesis of cortisol is missing, and so less cortisol produced, providing less negative feedback on the hypothalamus and anterior pituitary, and an increased ACTH is secreted.  This stimulates the adrenal gland to grow larger, and more androgen is secreted from the adrenal, so the genitals become masculinized.  So in CAH infants you'd expect to see an enlarged adrenal gland and an inability of the adrenal gland to respond to ACTH by secreting cortisol. 

a.  a grossly enlarged adrenal gland as seen by ultrasound  This WOULD indicate that CAH is possible, and the question asked which of these indicates that the infants DON'T have CAH.

b.  a shrunken adrenal gland as seen by ultrasound

The adrenal size is not sufficient indication of whether CAH is present, but since you'd expect an enlarged adrenal in CAH, then a small adrenal would preclude a CAH diagnosis, so we gave you credit for this answer.

c.  higher than normal levels of ACTH in blood  This could indicate that the infants DO have CAH and the question asked which indicate that they DON'T have it.

d.  higher than normal levels of androgens in blood  This could indicate that the infants DO have CAH (or some other disorder) and the question asked which indicate that they DON'T have it.

e.  high androgen secretion in response to an injection of LH LH stimulates the gonads.  In CAH, the ovaries are fine, and in response to LH they will secrete the usual estrogen, not androgens.  So response to LH does not allow us to eliminate CAH as a diagnosis.

f.  high cortisol secretion in response to an injection of ACTH  

This result would allow the doctors to definitely conclude that the girls do NOT have CAH, since CAH is characterized by an inability to secrete cortisol.  If they secrete high cortisol in response to ACTH, then they do not have CAH.

C.  During a usual pregnancy, the corpus luteum produces estrogen and progesterone for three months.  The estrogen and progesterone that are secreted later in pregnancy come from the placenta, which has grown large enough in the third month to be a significant steroid-secreting gland.  While pregnant with these infants, the mothers developed certain masculine traits, such as deeper voice, male-like body  hair, and an enlarged clitoris.  Did the mother have the same mutation as her infant?   a.  yes   b. no    Circle one and briefly explain why you chose this answer.   (20)

The mutated gene does not produce aromatase, which is needed to convert testosterone to estrogen.  Without the aromatase, an individual will not produce estrogen.  It is unlikely that the mother had this mutation, because if she did, she never would have produced estrogen, so never would have ovulated, and never would have gotten pregnant in the first place.  The mother developed masculine traits during pregnancy, which implies that she was exposed to androgens only during pregnancy.  Where did these androgens come from?  They could have come from the fetus, which lacks the aromatase, and so cannot produce estrogen.  They also could have come from the placenta, which is a steroid secreting gland, and exists only during pregnancy.  The placenta derives from the cells that originally made up the chorion, the membranes around the embryo, so the placenta is genetically similar to the fetus, and will contain the same mutation as the infant. 

2.   The author of www.milksucks.com argues that people should fill their dietary requirement for calcium by eating calcium-containing plants, such as broccoli, dried figs and collards, since milk is harmful and does not prevent osteoporosis.  To support his argument, he quotes Dr. Neal Barnard, president of the Physicians Committee for Responsible Medicine:  "It is hard to turn on the television without hearing commercials suggesting that milk promotes strong bones. The commercials do not point out that only 30 percent of milk's calcium is absorbed by the body or that osteoporosis is common among milk drinkers."     Do you find Dr. Barnard’s argument  a convincing reason to stop drinking milk?  Why or why not?  Your answer should refer to the bold text.   (10)

Barnard's argument is misleading, because he seems to be saying that milk is different from broccoli in that only 30 percent of milk's calcium is absorbed, but in fact about 30% of the calcium from any food source is absorbed through the small intestine; this isn't unique to milk. 

We gave partial credit for these answers:
30% absorption is enough, because if you drink lots of milk, 30% of that will give you enough calcium.
Even if milk doesn't provide much calcium, it would still be good to drink it, because it is supplemented with vitamin D, which is needed for absorption of calcium from other foods.

Note: This website is run by PETA, which is opposed to the use of animal products for any reason. 

3.  Scientists have been able to delete certain genes from experimental mice, so that the gene is completely “knocked-out” from all the mouse’s cells.  Assume there were mice born with knock-outs of the genes for the proteins listed below.  For each one, indicate which cell normally synthesizes this protein and would effect would the lack of this protein have on calcium.  (30; 10 each)  3 points for each blank;  7 points for explanation

a.  1-alpha hydroxylase is synthesized by ___kidney______________ (which tissue or organ) .  If it’s lacking, there will be less active vitamin D formed, less absorption of calcium from the small intestine, and possibly less calcium in the blood.

b.  cathepsin K, an enzyme that degrades bone matrix, is synthesized by ____osteoclasts___________ (which cells) .  If it’s lacking,  the osteoclasts will have fewer digestive enzymes, less ability to break down bone, less ability to replenish lowered blood calcium levels, and so blood calcium may fall.

 c.  the calcium-sensing receptor  is synthesized by ____parathyroid gland  (or C cells of the thyroid gland)____ (which cells) .  If it’s lacking in the parathyroid gland, then the parathyroid will not be able to sense when blood calcium levels fall, will not be able to respond by secreting PTH to raise blood calcium, and as a result, blood calcium levels will fall. 

If it's lacking in the C cells, these cells will not be able to sense when blood calcium is too high, and will not be able to secrete calcitonin to lower blood calcium.  This alone is not such a good answer, because if the receptor is lacking in C cells, it will also be lacking in PTH cells, and the PTH gland is much more important for blood calcium regulation, and so the lack of the receptor will cause symptoms there first.  However, we gave you credit for C cells, too.

d.   Which one of the above would be the most serious defect, and why?   (10)

c. The defects in a. and b. may lead to some decrease in blood calcium levels, but they are each affecting just one locus of control of blood calcium.  The defect in c. means that the body can't sense when blood calcium is low, and so can't respond by sending messages to any of the three possible sites (bone, kidney, small intestine), and so blood calcium can fall too low, which can be fatal.  You got partial credit for saying that the body won't be able to regulate blood calcium, without mentioning that the inability to RAISE blood calcium (via kidney, bone, small intestine) is much more serious than the inability to LOWER blood calcium, since high blood calcium is less likely to occur under normal conditions.