A 25-year-old man comes to the physician because he and his wife have been unable to conceive for the last 2 years. They have no children. Infertility evaluation is begun, and laboratory studies show a low sperm count. A more thorough evaluation elucidates a rare genetic abnormality that leads to permanently inactive FSH receptors. Which of the following substances is most likely decreased in this patient?

Question

A 25-year-old man comes to the physician because he and his wife have been unable to conceive for the last 2 years.  They have no children.  Infertility evaluation is begun, and laboratory studies show a low sperm count.  A more thorough evaluation elucidates a rare genetic abnormality that leads to permanently inactive FSH receptors.  Which of the following substances is most likely decreased in this patient?

Quizplus · Accepted Answer

Pulsatile secretion of gonadotrophin-releasing hormone from the hypothalamus stimulates the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the gonadotroph cells in the anterior pituitary. LH stimulates the release of testosterone from the Leydig cells in the interstitium of the testicles, and FSH stimulates the release of inhibin B from the Sertoli cells in the seminiferous tubules of the testicles. Testosterone and inhibin B induce negative feedback on LH and FSH production, respectively. FSH also stimulates the Sertoli cells to produce androgen-binding protein locally, within the seminiferous tubules. This androgen-binding protein is responsible for the high local testosterone concentration and is different from sex hormone-binding globulin, which is found in the blood. High local levels of testosterone and FSH are necessary for spermatogenesis. Defective FSH receptors will prevent spermatogenesis and cause low inhibin B levels, because FSH is responsible for both spermatogenesis and inhibin B production. (Choice A) FSH levels will be high in patients with FSH receptor defects because there is no negative feedback from inhibin B; inhibin B cannot be produced without proper functioning of the FSH pathway. (Choices B and D) LH and testosterone levels are likely to be normal in this patient because FSH does not play a role in either LH or testosterone feedback. Since the FSH receptor defect is isolated, this patient will have normal testosterone and LH levels. (Choice E) The circulating levels of other androgens such as DHEA, DHEAS, and androstenedione are also not affected by FSH. Educational objective: LH stimulates the release of testosterone from the Leydig cells of the testes; FSH stimulates the release of inhibin B from the Sertoli cells in the seminiferous tubules. Testosterone and inhibin B induce negative feedback on LH and FSH production, respectively.

A 25-Year-Old Man Comes to the Physician Because He and His