Spermatogenesis and male hormones

Gonadotropin-releasing hormone (GnRH) travels through the hypophyseal portal vessels to the anterior pituitary and drives release of the gonadotropins, LH and FSH.

• Correct: GnRH:
• TRH:
• CRH:

Meiosis I separates the homologous chromosomes of each pair, so each new cell is haploid; sister chromatids separate in meiosis II.

• Sister chromatids:
• Correct: Homologous chromosomes:
• The two strands of each DNA molecule:

Interstitial (Leydig) cells lie between the seminiferous tubules and make testosterone under the control of LH.

• Cells of the epididymis:
• Correct: Interstitial (Leydig) cells between the seminiferous tubules:
• Smooth muscle cells of the ductus deferens:

Meiosis I halves the chromosome number but leaves the sister chromatids joined, so a secondary spermatocyte has 23 double chromosomes.

• Spermatogonium: Spermatogonia are diploid stem cells with 46 chromosomes.
• Primary spermatocyte: A primary spermatocyte is diploid: 46 chromosomes, 92 chromatids.
• Correct: Secondary spermatocyte: Correct. Haploid with double chromosomes: the stage between meiosis I and meiosis II.
• Spermatid: A spermatid has finished meiosis II, so its 23 chromosomes are single.

Each primary spermatocyte gives two secondary spermatocytes, each of which gives two spermatids: 4 per primary spermatocyte. Spermiogenesis reshapes without dividing. 50 × 4 = 200 sperm.

• 50: Spermiogenesis does not divide cells, but meiosis does, twice.
• 100: 100 counts only one division. Meiosis has two.
• Correct: 200: Correct. Four sperm from each primary spermatocyte.
• 400: 400 would need a third division. Spermiogenesis only reshapes.

Self-tolerance was established in childhood, before meiosis began. Spermatocytes and spermatids make new surface proteins that white blood cells have never been taught to ignore, so they would be attacked as foreign. The Sertoli tight junctions keep antibodies and lymphocytes away from them.

• Spermatogonia need no nutrients from the blood, while the later cells need a great many of them: Spermatogonia need nutrients too; they get them directly from the blood side of the barrier.
• Correct: The later cells carry new proteins made after the immune system learned self-tolerance: Correct. The barrier shields cells whose proteins look foreign to the immune system.
• Spermatogonia are haploid and cannot be harmed by toxins: Spermatogonia are diploid, not haploid.
• The barrier stops sperm from leaving the tubule too early: Sperm are released into the lumen on the far side of the barrier; the barrier does not hold them back.

When the gonad fails, its products fall and the feedback brakes lift. The hypothalamus and pituitary push harder, so GnRH, LH and FSH rise, but the damaged testis cannot respond. Low testosterone with high LH and FSH is the pattern of testicular (primary) failure.

• Blood testosterone: down. The Leydig cells that make testosterone no longer work, so blood testosterone falls.
• Inhibin: down. Inhibin comes from the Sertoli cells, which have stopped working.
• GnRH pulses from the hypothalamus: up. With little testosterone, the brake on the hypothalamus is lifted, so it releases more GnRH.
• LH: up. Less testosterone braking the pituitary, and more GnRH driving it, raise LH.
• FSH: up. Both brakes on FSH, testosterone and inhibin, are gone, so FSH rises, usually even more than LH.
• Sperm count: down. Without working Sertoli cells and a high local testosterone level, spermatogenesis stops.

The injected androgen brakes the hypothalamus and pituitary, so GnRH, LH and FSH fall. Without LH, his Leydig cells stop making testosterone, and the very high local level inside the tubules is lost, along with FSH support. Spermatogenesis needs that local level, which blood testosterone from injections cannot reach. His testes also shrink. You can follow the same chain in the endocrine chapter's anabolic steroid scenario.

• Very high blood testosterone poisons the finished sperm directly while they are stored in the ducts: Testosterone is needed for spermatogenesis; it does not kill sperm.
• Correct: Negative feedback suppressed his LH and FSH, so the tubules lost their local testosterone and FSH: Correct. Suppressed LH and FSH remove the local drive to sperm production.
• The injections block the ductus deferens: Hormone injections do not block a duct; the problem is that few sperm are made.
• His Sertoli cells were converted into Leydig cells: Cells do not convert from one type to the other; both types simply lose their pituitary drive.

Chemotherapy kills rapidly dividing germ cells but usually spares the Leydig cells, so testosterone and LH stay normal. Sertoli cells supporting few germ cells release less inhibin, so the brake on FSH weakens and FSH rises on its own.

• His pituitary is making too much GnRH: GnRH comes from the hypothalamus, not the pituitary, and more GnRH would raise LH as well as FSH.
• His Leydig cells were destroyed, so they no longer make enough testosterone: If Leydig cells were destroyed, testosterone would be low and LH high.
• His testosterone receptor proteins no longer work: Broken receptor proteins would raise both testosterone and LH, because feedback would fail too.
• Correct: His germ cells were destroyed, so his Sertoli cells release less inhibin: Correct. Low inhibin selectively raises FSH.

Inhibin comes from the Sertoli cells, not the Leydig cells. It acts on the anterior pituitary to lower FSH release.

• The hypothalamus releases GnRH in pulses: This step is right. GnRH is released in bursts every 1 to 3 hours.
• GnRH makes the anterior pituitary release LH and FSH: This step is right. GnRH is the releasing hormone for both gonadotropins.
• LH drives the Leydig cells to make testosterone: This step is right. LH targets the Leydig cells.
• FSH and testosterone act on the Sertoli cells: This step is right. The Sertoli cells respond to both.
• Correct: Inhibin from the Leydig cells lowers FSH release: This is the error. Sertoli cells, not Leydig cells, make inhibin.

Testosterone enlarges the larynx, builds muscle, starts spermatogenesis and, through DHT in hair follicles, grows facial hair. Plate closure depends on estradiol made from testosterone by aromatase, so testosterone does not close the plates by itself.

• Correct: Deeper voice from a larger larynx: Correct. Testosterone enlarges the larynx and lengthens the vocal cords.
• Correct: Increased skeletal muscle mass: Correct. Testosterone speeds protein synthesis in skeletal muscle.
• Correct: Start of spermatogenesis: Correct. Spermatogenesis needs a high local testosterone level.
• Correct: Growth of facial hair: Correct. DHT acting on hair follicles drives male-pattern hair growth.
• Closure of the epiphyseal plates without any conversion: The plates close under estrogen. Men who cannot make or respond to estrogen keep growing into adulthood.