Reproductive physiology 1.

Androgens

Learning objectives: 85

Adrenal cortex (Zona reticularis) Androgens

Dehydroepiandrosterone sulfate

Dehydroepiandrosterone

Androstenedione

Testis (Leydig cells) Androgens

Testosterone

(Ovaries) (Androgens)

Genetic sex XY - XX chromosomes

Gonadal sex testes - ovaries

Phenotypic sex external features

Sex

Male reproductive system

Vas deferens

Epididymis

Testis

Seminiferous tubule

Leydig cell

Sertoli cell

Cholesterol

Pregnenolone

Progesterone

11-deoxycorticosterone

Corticosterone

18-OH-costicosterone

Aldosterone

Desmolase

3-HSDH

11-OH-ase

21-OH-ase

18-OH-ase

18-HSDH

17-OH-ase 17,20-lyase

aromatase

17-HSDH

17-OH-pregnenolone

17-OH-progesterone

11-deoxycortisol

Cortisol

Androstenedione

Estrone

Androstanediol

Testosterone

Estradiol

Biosynthesis of androgens in the testes

DHEA = Dehydroepiandrosterone

DHEAS = Dehydroepiandrosterone sulfate

Free: 2 %

Bound to protein:

-Albumin 54 %

- Gonadal steroid-binding globulin 44 %

Transport of testosterone in plasma

Metabolism of testosterone in some target tissues

Testosterone

5α-reductase aromatase

SKIN

ADIPOSE TISSUE

(brain, liver, Sertoli cells)

TESTIS

Dihydrotestosterone 17β-Estradiol

Androgenic potencies of androgens

Dihydrotestosterone : Testosterone : Dehydroepiandrosterone = 60 : 20 : 1

100x more

Testosterone

Testosterone Testosterone

aromatase

Estradiol

Mechanism of action

Testosterone

5α-reductase

Dihydrotestosterone

Effects

Y-chromosome

Sertoli cells

Leydig cells Testosterone

Dihydrotestosterone

Penis

Scrotum

Wolffian duct

Embryology of the reproductive system

Sex determining Y-gene

Embryonic

(indifferent)

Gonad

Embryonic

Testis

Müllerian duct

regression

factor

Müllerian duct

regression

Vas deferens

Seminal vesicle

Epididymis

Human chorionic gonadotropin (hCG)

of the placenta

32oC

Countercurrent exchanger mechanism for conservation of local

temperature and testosterone concentration in the testis

Testosterone

Testosterone Testosterone

aromatase

Estradiol

Mechanism of action

Testosterone

5α-reductase

Dihydrotestosterone

Differentiation of

male

external genitalia

Differentiation of

male

internal genital ducts

Differentiation of

male

hypothalamus

Plasma testosteron levels at various ages in human males P

lasm

a t

esto

ster

on

e (n

mo

l/l)

Fetal Neonatal

Prepubertal

Pubertal Adult Scenescence

birth

Age (years)

Biological effects of testicular androgens in male

PREPUBERTAL

Accessory sex organs (differentiation of the Wolffian duct)

External genitalia (differentiation and growth of the penis and scrotum)

PUBERTAL

Testis (hormonal support of spermatogenesis)

Accessory sex glands (growth and secretion of the prostate gland, seminal vesicle)

External genitalia (growth of the penis and scrotum)

Bone (Ca2+, PO43- retention, epiphysial closure)

Vocal cords (voice changes)

Skin (hair growth and loss, stimulation of sebaceous glands)

Skeletal muscle (anabolic action: protein synthesis) Doping!

Erythropoiesis (red bone marrow, production of erythropoietin)

CNS (libido)

Regulation of hormone secretion

GnRH

LH

Inhibin

Testosterone

GnRH: Gonadotropin-releasing hormone

FSH: Follicle-stimulating hormone

LH: Luteinizing hormone

limbic system

visual-, olfactory system

hours

feedback inhibition:

+ weak androgens, estrogens

fetus:

LH ≈ human chorionic gonadotropin (hCG) FSH

LH

Leptin

FSH

pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2

Glycoprotein hormones contain two

subunits, a common α subunit and a distinct

β subuit.

Blood-testis barrier

Testosterone

Blood-testis

barrier

Sperms develop 65-70 days long

Sperm production: 45-200 millions/day

NO androgen

receptors

Functions of Sertoli cells

1) It produces Müllerian duct regression factor

2) It provides nurishment to the developing spermatozoa

3) The intercellular junctions between adjacent Sertoli cells constitute the blood-testis

barrier

4) It produces Inhibin

5) It secrets Androgen-binding protein (ABP) and estradiol

6) It secrets plasminogen activator

7) It absorbs the unnecessary cellular organelles that are cast off from the spermatozoa

LH FSH

Carlo Maria Michelangelo Nicola Broschi

„Farinelli”

(1705 – 1782)

Vasectomy: It is a surgical procedure for male sterilization and permanent birth control. During the

procedure, the vasa deferentia of a man are severed and tied.

Castration: Before puberty: (eunuchoidism) tall body, narrow shoulders, less muscle, the genitalia

are small, the voice is high pitched, pubic and axillary hair are sparse

After puberty: secondary sex characteristics regress slowly, the voice remains deep,

some loss of libido

In the baroque music era

the „castrati” singers were

highly appreciated by

opera composers.