The document discusses testicular function and hormonal control. It notes that the testes contain two compartments - the tubular compartment containing seminiferous tubules where spermatogenesis occurs, and the interstitial compartment containing Leydig cells that produce testosterone. Spermatogenesis requires high intratesticular testosterone levels produced by Leydig cells under control of LH from the pituitary. The hypothalamus secretes GnRH to stimulate the pituitary to secrete LH and FSH. LH stimulates testosterone production and FSH supports spermatogenesis by acting on Sertoli cells. Inhibin and activin secreted by Sertoli cells provide local feedback regulation of FSH levels

2. BY:
DR. SAHEED OLUWASINA OSENI

5. Testis (sagittal view) Testis (cross sectional histological view of
the seminiferous tubules)

9. MAJOR CELLS RESPONSIBLE FOR TESTICULAR FUNCTION
GERM CELLS: spermatogonia to spermatozoa
SERTOLI CELLS: regulate germ cell development to
spermatozoa
INTERSTITIAL LEYDIG CELLS: that secrete testosterone,
the major androgen

11. Spermatogenesis and Androgens
 Spermatogenesis is obligatorily dependent on androgen
 Early events in spermatogenesis do not require androgens, but full
spermatogenesis is obligatorily dependent on androgens
(testosterone)
 Spermatogenesis is dependent on high intratesticular
concentrations of testosterone that are normally present in the
testis
 How does androgen act to support and promotes
spermatogenesis?

12. The testes produce the:
 male gametes (through spermatogenesis) and
 the male sexual hormones/androgens (through steroidogenesis).
 Spermatogenesis and steroidogenesis take place in two compartments
morphologically and functionally distinguishable from each other.
 These are the tubular compartment, consisting of the seminiferous tubules
(tubuli seminiferi) and the interstitial compartment (interstitium) between
the seminiferous tubules.
 The function of the testis and thereby also the function of its compartments
are governed by the hypothalamus and the pituitary gland.

13. Tubular compartment
 Sertoli cell: also known as the nurse or mother cells or sustentacular cells
support spermatogenesis.
 Their proliferation is triggered by testosterone and FSH secretion. FSH-
receptor on its membranes.
 Inhibin inhibits its proliferation.

14. Interstitial Compartment
 The most important cells of
this compartment are the
Leydig cells (the source of
testicular testosterone).
 Others are immune cells,
blood and lymph vessels,
nerves, fibroblasts and loose
connective tissue.
 Leydig cells: respond to luteinizing
hormone (LH) with steroid
production (primarily testosterone).
 Leydig cells are unusual in that they
rely on de novo synthesis of
cholesterol more than other cells
(50%).

17.  3 tiers of organization: Hypothalamus, Pituitary gland, Testis
Hypothalamus: GnRH (gonadotropin-releasing hormone)
Pituitary gland: LH (luteinizing hormone), FSH (follicle-stimulating hormone)
– LH: stimulates Testosterone production by Leydig cells in interstitium
– FSH: supports spermatogenesis by stimulating Sertoli cells in the
seminiferous epithelium
 Testis:
– Testosterone:
– Inhibin: secreted by Sertoli cells, suppresses FSH secretion by
gonadotropes;
– Activin: secreted by Sertoli cells, stimulate transcription of FSH B subunit

18. Functional Organization of the Hypothalamo-Pituitary
System
 The gonadotropins (luteinizing
hormone (LH) and follicle-
stimulating hormone (FSH)) are
produced and secreted by the
gonadotropic cells of the anterior
pituitary.
 they control steroidogenesis and
gametogenesis in the testis.
 They are regulated by the
hypothalamic gonadotropin-
releasing hormone (GnRH)

23. Hormonal control of testicular function
 At puberty, secretion of gonadotropin-releasing hormone (GnRH) increases
 Stimulates anterior pituitary to increase secretion of luteinizing
 hormone (LH) and follicle-stimulating hormone (FSH)
 LH stimulates Leydig cells to secrete testosterone
 Testosterone stimulates spermatogenesis, Synthesized from cholesterol in testes
 Suppresses secretion of LH and GnRH via negative feedback
 Enzyme 5 alpha-reductase converts testosterone into dihydrotestosterone
(DHT) in external genitalia and prostate
 FSH acts indirectly on spermatogenesis

24. Cont’d of hormonal control of testicular function
 FSH and testosterone act on Sertoli cells to promote spermatogenesis and
stimulate secretion of androgen-binding protein (ABP)
 ABP binds testosterone keeping concentration high for spermatogenesis.
 Inhibin suppresses the effects of FSH locally in the testes as well as FSH
secretion by the pituitary.
 Activin locally opposes the effects of inhibin.

26. SUMMARY OF HORMONAL EFFECT ON TESTICULAR FUNCTION

28.  3 tiers of organization: Hypothalamus, Pituitary gland, Testis
 Hypothalamus: GnRH (gonadotropin-releasing hormone)
 Pituitary gland: LH (luteinizing hormone), FSH (follicle-stimulating
hormone)
– LH: stimulates Testosterone production by Leydig cells in interstitium
– FSH: supports spermatogenesis by stimulating Sertoli cells in the
seminiferous epithelium
– Inhibin: secreted by Sertoli cells, suppresses FSH secretion by
gonadotropes; ? Use of Inhibin B as marker for impaired testicular
function
– Activin: secreted by Sertoli cells, stimulate transcription of FSH B subunit

30. Developmental Male hormonal testicular
function
 Leydig cell differentiation
– 1st wave - 7 weeks gestation: stimulated by Human Chorionic
Gonadotropin from placenta; androgens appear in circulation
– 2nd wave - 2-3 months after birth: stimulated by gonadotropin
production from neonate’s pituitary; briefly elevates Testosterone
– Androgens produced during first 2-6 months of life are thought to
hormonally imprint hypothalamus, liver, prostate, phallus & scrotum
– Leydig cells of infants then regress & testes are dormant until puberty.
 Puberty
– Hypothalamus generates pulses of GnRH around 12th year of life
– Onset of GnRH pulses typically occurs at night, due in part to
gradual decrease in nocturnal melatonin secretion from pineal gland
– Also influenced by nutritional status of body and growth rate
• GH & IGF-1 stimulate reproductive function
• Leptin determines size of fat stores in body - ? Role in puberty

31.  Aging of Hypothalamic/Pituitary Axis
– Testosterone: levels decline at > 50 years of age
– LH: basal levels increase in older men; LH pulsatility is
blunted
– Leydig cells: steroidogenic capacity decreases
– Spermatogenesis: lower fecundity at > 40 years, 50%
lower probability of achieving pregnancy w/in 1 year
compared to men < 25 years of age.

34. QUESTIONS
1. In the male, LH causes
A) initiation of spermatogenesis.
B) development of secondary sex
characteristics.
C) testosterone production.
D) ejaculation.
2. A function of FSH in the male is to
A) inhibit progesterone.
B) initiate testosterone production.
C) increase protein synthesis.
D) initiate spermatogenesis.
3. Testosterone is produced by
A) Sperm cells.
B) Sertoli cells.
C) Leydig cells
D) the hypothalamus.
4. What s the action of inhibin in the male reproductive
system?
A) It slows down the release of testosterone
B) It initiates the process of spermatogenesis
C) It initiates the release of testosterone from the leydig
cells
D) It slows down the production of spermatozoa
5. What happens do you think will be the consequence of
each of the following?
A) If the sertoli cells fails to secrete a inhibin or activin for a
negative feedback mechanism.
B) If the adenohypophyseal cells fails to secrete FSH.
C) If the pituitary gland becomes cancerous and is producing
excess of LH.
6. All of the following phase is androgen independent excepts
A) Spermatogonia Primary spermatocyte
B) Primary spermatocyte Secondary spermatocyte
C) Spermatid Spermatozoa

35. REFERENCES
 William H. walker (2011), Testosterone signaling and the regulation of
spermatogenesis, Landes Bioscience, Spermatogenesis 1:2, 116-120.
 Gerhard F. Weinbauer, Craig Marc Luetjens, Manuela Simoni, and Eberhard
Nieschlag (2010) ,Physiology of Testicular Function, Andrology, DOI:
10.1007/978-3-540-78355-8_2, © Springer-Verlag Berlin Heidelberg.