Lecture 45:endocrine Functions of The Testes: DR Shamshad

Lecture 45 :Endocrine functions of the
Testes
Dr Shamshad
Objectives:
1. Identify the different sex hormones secreted by tesits and
contrast their biological activity.
2. Describe the mechanism of action and the physiological
effects of testicular androgens relating them to age.
3. Identify the role of testosterone in male puberty.
4. Discuss the role of hypothalamuo-hypophyseal -testiclar
axis.
5. Correlate this knowledge to the pathogenesis of the male
hypogonadism.
Hormones secreted by Testes
Androgens Others
• Testosterone o Inhibin B and Activins
• Dihydrotestostereone:DHT o Anti-Mullerian
• Pregnenolone hormone(Mullerian -
• Progestrone inhibiting substance,MIS)
• 17-OH progestrone o Insulin -Like factor 3
• Andosterndione
• Oestradiol
Androgens
All Androgens are steroid compounds
Both in the testes and in adrenals androgens are synthesised from

precursor cholesterol
Testosterone is considered as primary testicular hormone
Testosterone is converted into Active hormone Dihydrotestosterone

(DHT) in the target tissues for further action.
Pathways of Testosterone biosynthesis
Desmolase
3 -β-hydroxysteroid dehydrogenase
17, 20-desmolase
17, 20-desmolase
3 -β-hydroxysteroid dehydrogenase Aromatase
17 β-hydroxysteroid dehydrogenase 17 β-hydroxysteroid dehydrogen

17 β-hydroxysteroid dehydrogenase
Aromatase
3 β-hydroxysteroid dehydrogenase
GnRH secreted from the hypothalamus releases
(LH from the pituitary.
LH binds to LH receptors on Leydig cells,
stimulates Gs, and activates the cAMP/protein
kinase A (PKA) pathway.
PKA promotes the transport of cholesterol into
mitochondria and increases transcription of genes
involved in testosterone biosynthesis.
Cholesterol is converted to pregnenolone, which
diffuses into the endoplasmic reticulum for
testosterone biosynthesis via ∆4 and ∆5
pathways.
Testosterone is formed by 17β-hydroxysteroid
dehydrogenase 3 (HSD17β3) in the ∆4 pathway
and by 3β-hydroxysteroid dehydrogenase
(HSD3β) in the ∆5 pathway.
Testosterone is converted to dihydrotestosterone
(DHT) by 5α-reductase,
and some are aromatized to 17ß-estradiol.
3x more potent than
Testosterone
Sex hormone binding globulin (SHBG) :act as carrier protein for
Testosterone & Estradiol
-SHBG has 3 fold higher affinity for testosterone
-Synthesised mainly in liver
-Regulated by the opposing actions of sex steroids
-Androgens inhibits SHBG synthesis
-Estrogen stimulates SHBG synthesis
Applied: Increase plasma SHBG - acute decrease in free testosterone
Concentration of Androgen in normal male adult
Functions of male sex hormones-Testosterone
Important sex hormone in male
Development and functioning of the male phenotype
Stages Effect of testosterone
In utero :Fetal life Sex differentiation
Puberty Virilization
Adulthood Maintenance of the male
phenotype
Sexual function
Anabolic effects
Fetal life :
Prenatal sex differentiation
-Differentiation & Maturation of wolffian duct
-Suppresses formation of female genital organs in male fetus
-Development of penis,scrotum,prostate, seminal vesicle & male
genital duct
-Descent of testis through inguinal canal into scrotum during last two
months of gestation.
Applied:In case of undescended testis administration of testosterone
helps descent of testis.If left may lead to malignancy of testis
Target Functions
Sex organs Virilization & development of testes,penis,epididymis,seminal vesicle &

prostrate.Initiation & maintenance of spermatogenesis.
Muscles Increase: Muscle mass, lean body mass, Anabolic effect on muscles
Skin and Increase: sebaceous secretion , acne formation, male distribution of hair,
hair temporal baldness
Skeletal Pubertal growth spurt: Increase: bone matrix thus bone density,Calcium salts
organs deposition,Accelerate linear growth, closure of epiphysis of endplates of bone,
Funnel shaped pelvis with narrow outlet,strengthening of pelvis
Blood cells Erythropoiesis:Stimulate erythropoietin from kidney, stimulate stem cells,

increase Hb synthesis
Increase: production of clotting factors

Decrease:Anti-inflammatory effect: suppression of humoral and cellular
immunity
Liver Increases: fibrinogen, hepatic triglyceride lipase,alpha1 antitrypsin,
haptoglobin
Decreases:SHBG ,hormone binding proteins, transferrin, fibrinogen
Lipids Increases: Plasma HDL concentration

Decreases: Plasma cholesterol, LDL and triglycerides concentration.
Proteins: Increases: Activities of all cells,enzymes production,BMR, protein synthesis
Anabolic:
Electrolyte & Reabsorption of sodium in distal tubules, water retention,

water balance Increases ECF and blood volume hence body weight
Bl.glucose Decrease:Fasting blood glucose, HbA1c
Brain Increases:sex drive, Libido,Improves cognitive function, socialization,

confidence, concentration, neuroprotective actions,mood, spatial
orientation,aggression,Male voice
Decreases: anxiety,depression,verbal abilities.
Degradation and Excretion of Testosterone
Free testosterone is rapidly converted mainly by the liver into
Androsterone and Dehydroepiandrosterone.
Conjugated either to Glucuronides or Sulfates
Conjugated metabolites are excreted either into the gut through

liver bile Or into urine through kidneys.
Testosterone Regulation
hCG(Human Chorionic Gonadotropins)
Fetal life:
hCG secreted by placenta stimulate testosterone secretion by the

fetal testes
This testosterone is important for formation of male genital organs

in fetus.
Inhibin
Inhibin:Glycoprotein with molecular weight b/w 10k-30k
Isolated from Sertoli cells in males & granulosa cells in females
Action: Potent inhibitory feedback effect on the Ant pituitary gland

mainly FSH
Provides important Negative feedback mechanism for control of

spermatogenesis
Inhibin
Polypeptide 3 subunits :glycosylated α subunit &
two non glycosylated β subunits βA and β B
Activins: heterodimers stimulates FSH
Details not known
Inhibins & Activins also found in brain, bone marrow & other tissues
Actions:In bone marrow activins helps development of WBCs.
In embryonic life, activins are involved in mesoderm formation
Bound :
In plasma ,α2 macroglobulins binds activins and inhibins .
In tissues activins bind to glycoproteins ,follistatins.
Class Activity Complex Dimer subunits
1 2
Inhibits FSH Inhibin A
α βA
Inhibin secretion
Inhibin B α βB
Activin A βA βA
stimulates
Activin FSH Activin AB βA βB
secretion
Activin B βB βB
Follistatin:
A Pituitary autocrine glycoprotein
Inhibits secretion of FSH by binding to and blocking the action of
Activitins
Kisspeptins: a family of neuropeptides localised to the arcuate
nucleus in the brain,
Which are upstream stimulators of GnRh secretion.
GnIH :Acts by regulating GnRh and may also operate at the level
of the testes as regulators of steroidogenesis
Hypogonadism
Fetal life:When the testes of the male fetus are nonfunctional
during fetal life none of the male characteristics develop
.Develop female sex organs.
Childhood:If boy loses his testes before puberty : Eunuchism

ensues Infantile sex organs and sex characters slightly tall.
Adulthood:If man is castrated after puberty:secondary sexual

character not affected .Decreased sex desire and impotence
and sterility.Accessary sexual organs dysfunction gradually
Adiposgenital
dystrophy syndrome
Froehlich's syndrome
Rare disorder
Characterized by:
Obesity, growth and
genital organ retardation
Type of Primary Secondary
Hypogonadism
Site Testes Pituitary gland,
hypothalamus
Serum Decreased Decreased
Testosterone
FSH and LH Increased No changes, or
decreased
Causes Klinefelter’s Kallman’s
syndrome syndrome
Primary: prepubertal onset:Eunuchoidism
Causes: Klinefelter's syndrome
● Chromosomal abnormalities
● Mutation of gonadotropin receptors genes
● Cryptorchidism
● Congenital anorchia
Signs and symptoms:
● Lack of adult male hair distribution
● High pitched voice
● Infantile genitalia
● Increased feminine type fat deposition
● Upper /lower segment ratio <1
Secondary: prepubertal onset
● Hypogonadotropic Hypogonadism :
Kallmann’s syndrome
● Delayed puberty development ,micropenis,maldescended testes, renal
agenesis
● Cleft lip and palate ,oligodontia, digit malformation
● Corpus callosum agenesis
Primary post pubertal onset:
Causes:
● Infection: Mumps orchitis , radiations
● Trauma
● Bilateral orchiectomy
● Autoimmune damage
● Chronic diseases: Cirrhosis of liver
● HIV
Signs and symptoms:
● Loss of libido
● Impotence
● Infertility

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Lecture 45 :Endocrine functions of the

Both in the testes and in adrenals androgens are synthesised from

Testosterone is considered as primary testicular hormone

Testosterone is converted into Active hormone Dihydrotestosterone

17 β-hydroxysteroid dehydrogenase 17 β-hydroxysteroid dehydrogen

Sex organs Virilization & development of testes,penis,epididymis,seminal vesicle &

Blood cells Erythropoiesis:Stimulate erythropoietin from kidney, stimulate stem cells,

Increase: production of clotting factors

Lipids Increases: Plasma HDL concentration

Electrolyte & Reabsorption of sodium in distal tubules, water retention,

Bl.glucose Decrease:Fasting blood glucose, HbA1c

Brain Increases:sex drive, Libido,Improves cognitive function, socialization,

Conjugated either to Glucuronides or Sulfates

Conjugated metabolites are excreted either into the gut through

hCG secreted by placenta stimulate testosterone secretion by the

This testosterone is important for formation of male genital organs

Isolated from Sertoli cells in males & granulosa cells in females

Action: Potent inhibitory feedback effect on the Ant pituitary gland

Provides important Negative feedback mechanism for control of

Childhood:If boy loses his testes before puberty : Eunuchism

Adulthood:If man is castrated after puberty:secondary sexual

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