W3006  Physiology         Fall 2002          Mini-Exam #1           NAME___________________________

 10 points each question.     Total possible:  80 points.   

 Answers in red.  Explanations in blue.

 1. The “New route from brain to testes” that was discovered by Catherine Rivier enables the brain to affect the testes by a signal that is best described as     a.  autocrine      b.  endocrine     c.  exocrine     d.  neurocrine      e.  juxtacrine   

The pathway she described is neuronal, and neurotransmitters are considered neurocrine signals. 

 2.  The radioimmunoassay described in class would require which of the following?  Circle all correct answers.

 a.  castrated roosters  This is required for the bioassay described
b.  radioactively-labeled hormone
c.  radioactively-labeled antibody Nonradioactive antibody was required for the RIA
d.  purified hormone which is not radioactive
e.  hormone receptors  Antibodies are not hormone receptors!
f.  an enzyme that can act on a particular substrate to cause a change in color of that substrate  This is required for the ELISA

3.  In the developing fetus, the testes are inside the abdominal cavity, and shortly before birth they descend into the scrotum.  In a condition called cryptorchidism, the testes do not descend into the scrotum, but rather remain within the abdominal cavity.  In this condition, you would expect that the testes produce                a. testosterone, but not sperm    b. sperm, but not testosterone              c. both sperm and testosterone          d. neither sperm nor testosterone
Steroid hormone synthesis can occur at the temperature of the abdominal cavity – that’s where the ovaries and adrenal glands are, and synthesize estrogen, progesterone, cortisol, aldosterone.  But sperm production requires the cooler temperatures found in the scrotum.

4.  Which of the following are important for keeping the testes cool in hot weather:   Circle all correct answers.
a.  Hair on the scrotum stands upright (piloerection).  b.  The muscles in the scrotum that are responsible for “shrinkage” begin to contract rhythmically, causing release of heat from the scrotum.  Muscle contraction occurs in cold weather, and the released heat would warm the scrotum.
c.  The muscles in the scrotum that are responsible for “shrinkage” begin to relax, causing a stretching of the scrotum and an increase in surface area of scrotal skin. 
d.  Smooth muscle around the blood vessels in the scrotum contract, leading to vasoconstriction.
e.  Sweat glands on the scrotum are activated.
Piloerection, muscle contraction that releases heat, and vasoconstriction all occur in cold weather, and would serve to produce heat and/or prevent loss of heat from the scrotum.    A larger surface area of skin provides more surface in contact with the air, so that more heat exchange takes place, plus provides a greater surface for spread and evaporation of sweat, which also cools the scrotum.

Questions 5-7 refer to the article summarized on the other side.

5.  The investigators measured bioactive LH using a bioassay based on Leydig cells from mice.  In drawing a dose-response curve, the “response” that they measured was probably   a.  testosterone secretion       b. thyroid hormone secretion    c.  inhibin secretion   d.  prostaglandin secretion    e. sperm production   f.  androgen-binding protein

LH stimulates release of testosterone from Leydig cells.

6.  Four baboons were castrated before puberty, then treated with testosterone at around the time they should have begun puberty.  This testosterone was probably   a. dissolved in water   b. dissolved in oil   c. enclosed in silastic 
Testosterone is a steroid, so dissolves better in oil than in water, and you could administer it this way, but for it to be present in the body for up to 15 months, as described in this article, it would need to be administered in a silastic implant, which allows for slow release of the hormone.

7.   The authors found similar results for immunoreactive-LH and bioactive-LH.  But let’s suppose that they found the following results:  Right after castration, immunoreactive-LH was high, while bioreactive-LH stayed low.  Three months later, both bioactive-LH and immunoreactive-LH were high.  Which of the following explanations would best explain these results:

a.  The technicians doing the immunoassay were more careful than the ones doing the bioassay.  
b.  LH can be secreted in more than one form, which differ slightly in their amino acid sequence.   There have, in fact, been several isoforms of LH found, and so a reasonable hypothesis might have been that the particular type of LH that is secreted changes around the time of puberty.  The results, however, don't support his hypothesis.
b.  Right after castration, some molecule like hCG has  LH-like activity on target cells, and only 3 months later is LH secreted. If some other molecule were exerting an LH-like effect on target cells, than you'd expect the target cells (Leydig cells, in the assay) to give a positive response, and bioactivity would be high initially, but it's not.
d.  Right after castration, Leydig cells do not have receptors for LH;  These receptors develop only after 3 months.  Not relevant.  Leydig cells are in the testes, and the testes are removed in castration, so Leydig cell receptors are not going to develop 3 months later.  The Leydig cells used in the mouse bioassay are equivalent each time the assay is used, so they wouldn't change over time. 
c.  Right after castration, LH is secreted in large amounts, but after three months, a liver enzyme is produced which destroys the LH.  If LH were enzymatically destroyed, you'd expect its bioactivity to decrease, but in fact it increases after 3 months.   

8.  It is known that at puberty, gonadotropin secretion increases.  The authors conclude that puberty in baboons is partly due to “alterations in negative androgenic feedback sensitivity on gonadotrophin secretion”.    Which one of the results in their study led them to draw this conclusion?  Explain your answer.

".....Administration of testosterone resulted in temporary suppression of B-LH, IR-LH and IR-FSH levels; however gonadotrophin levels subsequently rose with age despite increased testosterone levels."   Usually, testosterone exerts negative feedback effects on the hypothalamus and anterior pituitary gland, so that LH and FSH would be expected to decrease.  This happens, but the effect is only temporary, and after a while, the gonadotropin hormone levels increase again, indicating that negative feedback is no longer working as it had been. 

 

 

J Pediatr Endocrinol Metab 1997 Jul-Aug;10(4):401-10

 


Androgen effects on bioactive and immunoreactive gonadotrophin levels during puberty in male baboons.

Crawford BA, Spaliviero J, Simpson J, Handelsman DJ.

Department of Medicine, University of Sydney, Australia.

The effect of androgens on changes in circulating LH and FSH during pubertal development was examined longitudinally in a 3 year study in male hamadryas baboons. Baboon LH and FSH were measured by a species-specific radioimmunoassay and bioactive LH (B-LH) was measured by the mouse in vitro Leydig cell bioassay. Control baboons (n = 5) progressed normally through puberty. Eight baboons were castrated prepubertally; of these four received testosterone implants at the chronological age (CA) of clinical puberty (4.0 +/- 0.1 yr, mean +/- SEM). The timing of the postcastration rise in B-LH levels ranged between 1 and 15 months later (median 3.5 months) (CA 3.5 +/- 0.2 yr) in those with and without the testosterone implant, thus supporting the hypothesis that central activation of gonadotrophins occurs at the time of puberty, independent of gonadal influences. Similar results were seen for immunoreactive-LH (IR-LH) and IR-FSH levels. IR- and B-LH levels continued to rise with age (P < 0.0003) in the untreated castrated baboons, associated with an increased LH B/I ratio. Administration of testosterone resulted in temporary suppression of B-LH, IR-LH and IR-FSH levels; however gonadotrophin levels subsequently rose with age despite increased testosterone levels.   Thus the mechanisms initiating puberty involve both gonad-independent events as well as alterations in negative androgenic feedback sensitivity on gonadotrophin secretion.

           stuff in italics added for exam question.