HORMONAL CONTROL OF TESTICULAR FUNCTION

SAHEED OLUWASINA OSENI (DVM)

REPRODUCTIVE ENDOCRINOLOGY CLASS PRESENTATION

FLORIDA ATLANTIC UNIVERSITYDEPARTMENT OF BIOLOGICAL

SCIENCES

HORMONAL CONTROL OF TESTICULAR FUNCTION

BY:

DR. SAHEED OLUWASINA OSENI

HORMONAL CONTROL OF

TESTICULAR FUNCTION

MALE REPRODUCTIVE SYSTEM

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

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

What drives spermatogenesis?

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?

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.

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.

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%).

What drives androgen production by Leydig cells??

Hypothalamo-pituitary-testicular hormones 3 tiers of organization: Hypothalamus, Pituitary gland,

TestisHypothalamus: 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

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)

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

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.

SUMMARY OF HORMONAL EFFECT ON TESTICULAR FUNCTION

Male Reproductive Axis 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

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

Male Reproductive Axis 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.

QUESTIONS &

ANSWERS

QUESTIONS

1. In the male, LH causesA) initiation of spermatogenesis.B) development of secondary sex characteristics. C) testosterone production.D) ejaculation.2. A function of FSH in the male is toA) inhibit progesterone.B) initiate testosterone production.C) increase protein synthesis.D) initiate spermatogenesis.3. Testosterone is produced byA) Sperm cells.B) Sertoli cells.C) Leydig cellsD) the hypothalamus.

4. What s the action of inhibin in the male reproductive system?A) It slows down the release of testosteroneB) It initiates the process of spermatogenesisC) It initiates the release of testosterone from the

leydig cellsD) It slows down the production of spermatozoa

5. What happens do you think will be the consequence of each of the following?E) If the sertoli cells fails to secrete a inhibin or

activin for a negative feedback mechanism.F) If the adenohypophyseal cells fails to secrete

FSH.G) If the pituitary gland becomes cancerous and is

producing excess of LH.

6. All of the following phase is androgen independent exceptsH) Spermatogonia Primary spermatocyteI) Primary spermatocyte Secondary

spermatocyteJ) Spermatid Spermatozoa

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.

THANKS FOR LISTENING