Male Sex Hormone

Ricardo R. Santos, MD
 Classification of Steroid Hormones
A. Hormones of the gonads
1. Testicular hormone (male sex hormone)
- testosterone
- dihydrotestosterone (DHT)
2. Ovarian hormone (female sex hormone)
a. Estrogen
- estradiol, estrone, estriol
b. Progestin
- progesterone
 Classification of Steroid Hormones
According to number of carbon atoms in the side
chain
A. C 21 steroid (pregnane group)
- cortisol, aldosterone, progesterone
B. C 19 steroid (androstane group)
- testosterone, dehydroepiandrosterone,
androstenedione
C. C 18 steroid (estrane group)
- estradiol
D. C-27 steroid
- 1,25 dihydroxyvitamin D3
 Conversion of cholesterol to sex hormones
Cholesterol (C-27)
cytochrome P450 scc hydroxylase
Pregnenolone (C-21) DHEA
2C side chain cleavage;
17α- hydroxylase
3β- dehydrogenase aromatase
Δ4,5- isomerase
17-reductase
Progesterone (C-21; corpus luteum)
17α- hydroxylase
2C side chain cleavage
17- dehydrogenase Testosterone (C-
19) 17β- Estradiol (C-18)
Male Sex Hormone
 Testes Produce Testosterone and Spermatozoa
Carried out by 3 specialized cell types:
1. Spermatogonia – located in seminiferous tubules
2. Leydig cells (interstitial cells) – scattered in the
connective tissue bet. the coiled seminiferous tubules
- produce testosterone in response to LH
3. Sertoli cells – form the basement membrane of the
seminiferous tubules
- provide the environment necessary for germ cell
differentiation and maturation
- spermatogenesis is stimulated by FSH and LH
 Pathways of Testosterone Synthesis
Pregnenolone Progesterone
17α- hydroxylase 17α- hydroxylase
C17, 20 lyase C17, 20 lyase

Dehydroepiandrosterone Androstenedione
17β- dehydrogenase 17β-dehydrogenase

Δ5- Androstenediol
3β- dehydrogenase
Δ4,5- isomerase
Testosterone Testosterone
DHEA Pathway Progesterone Pathway
 Transport of Testosterone in the Blood
 Testosterone is transported in the blood by sex
hormone binding globulin (SHBG) produced in
the liver.
 SHBG is increased by estrogen, in certain types of
liver disease and hyperthyroidism.
 Decreased by androgens, advancing age and
hypothroidism.
 Testosterone binds to SHBG with higher affinity than
does estradiol.
 Albumin also binds testosterone in the blood.
 Only a small fraction (1 - 3% ) of testosterone in the
blood is in the free biologically active form.
 Metabolism of Testosterone
A. Metabolic pathways
1. Oxidation at 17- position producing 17-ketosteroids,
androsterone and etiocholanolone, which are
conjugated with glucuronide and sulfate in the liver

2. Reduction of A ring double bond catalyzed by NADP-

dependent 5α- reductase producing the potent
metabolite dihydrotestosterone (DHT).
- occurs primarily in prostate, external genitalia and
skin
- about 5 mg of testosterone and 400 ug of DHT are
produced daily
Metabolism cont.
Two forms of 5α- reductase:
a) Type I – predominantly expressed in the liver
b) Type II – expressed in reproductive tissues and
peripheral targets; mutations of this enzyme is
associated with male pseudohermaphroditism
3. About 1 – 5% of testosterone are converted to estradiol.
 Regulation of Testicular Function
 LH stimulates steroidogenesis and testosterone
production by binding to receptors on the plasma
membrane of Leydig cells.
 FSH binds to the Sertoli cells and promotes the
synthesis of androgen-binding protein (ABP).

 ABP transports testosterone in high concentrations to

the site of spermatogenesis.
 Sertoli cells also produce inhibin which participates in
sperm and testosterone production by regulating FSH
secretion through a negative feedback loop.
 Biologic Effects of Testosterone
 Sexual differentiation
 Spermatogenesis
 Development of secondary sexual organs and
ornamental structures
 Anabolic metabolism and gene regulation
 Male pattern behaviour