Lecture #18: Reproductive Endocrinology of the Male Testes

I.  INTRODUCTORY COMMENTS

1.  The gonads have two major functions: to produce spermatazoa and androgens.

2.  Anatomy: tunica albuginea, seminiferous tubules, epididymis.  (Fig. 17.1)

3.  Myoid cells are present in walls of seminiferous tubules.

4.  Type-A spermatogonia produce more spermatogonia, type-B spermatogonia enter spermatogenesis.

II.  GnRH AND PITUITARY GONADOTROPINS

1.  In males, GnRH is released in pulses to prevent down-regulation of gonadotropes.

2.  Pulses of LH are released about every 90 minutes.

3.  In many mammals, LH is released upon sight and/or smell of a female.

4.  Cellular targets for LH and FSH:

a.  LH specifically binds to interstitial cells of Leydig.

b.  FSH specifically binds to seminiferous cells of Sertoli.  (connected by tight junctions)

5.  Cellular actions of LH and FSH:

a.  LH increases Leydig cAMP and stimulates P450scc activity for steroidogenesis.  (Fig. 17.4)

b.  FSH stimulates:

(1)  cAMP-mediated production of androgen-binding protein.  (Fig. 17.4)

(2) transport of testosterone into seminiferous tubules and epididymis for sperm maturation.

(3)  acts synergistically with LH on Leydig cell steroidogenesis.

(4)  the number of LH receptors on the surface of Leydig cells.

(5)  conversion of testosterone to dihydrotestosterone in Sertoli.

(6)  inhibin secretion by Sertoli cells, to inhibit further FSH secretion.  (Fig. 17.3)

III.  SYNTHESIS, CHEMISTRY, AND METABOLISM OF ANDROGENS (Fig. 15.3)

1.  Leydig cells convert pregnenolone mainly to 17a-hydroxypregnenolone (instead of to P₄).

2.  Testosterone is the principal steroid produced in the testes.

4.  Testosterone in blood is bound to carrier proteins as follows:

a.  40% bound to gonadal steroid-binding globulin,

b.  40% bound to albumin,

c.  17% bound to other proteins.

5.  Testosterone is metabolized in the liver mainly to:

a.  androsterone and etiocholanolone (Fig. 17.2)

b.  both of these are excreted in urine in form of glucuronide and sulfate conjugates.

IV.  PHYSIOLOGICAL ROLES OF ANDROGENS

1.  Androgens needed to maintain spermatogenesis, after initiated by FSH.

2.  Androgens develop secondary sex characteristics, e.g., sex hair, shoulder girdle, vocal cords.

3.  Androgens stimulate erythropoiesis of blood stem cells in bone marrow.

4.  Androgens act similar to “anabolic steroids” on skeletal muscle.

5.  Androgens mediate their actions through nuclear receptors to stimulate transcriptional and translational processes related to protein synthesis. (see Figure 17.6)/

V.  ALCOHOL AND THE TESTES (chronic alcoholics)

1.  Excess alcohol induces aromatase to convert T to estrogens by adipose cells.

2.  The elevated estrogens can suppress gonadotropin secretion.

3.  Alcohol causes Leydig cell damage and loss of testosterone receptors.

4.  Alcohol decreases cAMP levels in Leydig cells.

5.  Prolonged cannabinoid intake also leads to diminished spermatogenesis.