This lecture discusses endocrine functions of the testes. It identifies hormones secreted by the testes including testosterone and DHT. It describes the mechanism of action of testicular androgens and their physiological effects relating to age and roles in male puberty. Finally, it correlates this knowledge to the pathogenesis of male hypogonadism.

1. Lecture 45
Endocrine functions of the Testes
Dr Shamshad
Majamaah University
KSA

2. 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. Objectives:
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.

4. Hormones secreted by Testes
Androgens Others
1. Testosterone
2. Dihydrotestostereone:DHT
3. Pregnenolone,Progestrone
4. 17-OH progestrone
5. Andosterndione
6. Oestradiol
I. Inhibin B and Activins
II. Anti-Mullerian hormone
(Mullerian -inhibiting
substance,MIS)
I. Insulin -Like factor 3

6. Androgens
Androgens precursor : cholesterol
Testosterone: Primary testicular hormone
In target tissues for further actions :
Testosterone  (Active) Dihydrotestosterone (DHT)

7. Desmolase
3 -β-hydroxysteroid dehydrogenase
17 β-hydroxysteroid dehydrogenas
3 -β-hydroxysteroid dehydrogenase
17 β-hydroxysteroid dehydrogenase
3 β-hydroxysteroid dehydrogenase
17 β-hydroxysteroid dehydrogenase
17, 20-desmolase
17, 20-desmolase
Aromatase
Aromatase
Pathways :Testosterone biosynthesis

9. 3x more potent than Testosterone

11. Steroid %
Free
% Bound to
Corticosteroid
Binding Globulin
Gonadal
Binding
Globulin
Albumin
Testosterone 2 0 65 33
Androsterond
ione
7 0 8 85
Estradiol 2 0 38 60
Progesterone 2 18 0 80
Cortisol 4 90 0 6

12. Sex hormone binding globulin (SHBG) :Carrier protein
SHBG has 3 fold higher affinity for testosterone
Synthesized mainly in liver
Regulated by the opposing actions of sex steroids
Androgens inhibits SHBG synthesis
Estrogen stimulates SHBG synthesis

14. Concentration of Androgen in normal male adult
Plasma testosterone
(Free & bound)
Adult male Adult female
ng/dL 300-1000 30-70
nmol/L 10.4-34.7 1.04-2.43

15. Functions :Testosterone
Important sex hormone in male
Development and functioning of the male phenotype
Stages Testosterone Effect
In utero :Fetal life Sex differentiation
Puberty Virilization
Adulthood Maintenance of the male phenotype
Sexual function
Anabolic effects

16. 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: Cryptorchidism (undescended testis )
Testosterone administration .
If left untreated may lead to testicular cancers.

17. 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
hair
Increase: sebaceous secretion , acne formation, male
distribution of hair, temporal baldness

18. Skeletal
organs
Pubertal growth spurt: Increase: bone matrix thus bone
density,Calcium salts 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

19. 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:
Anabolic:
Increases: Activities of all cells,enzymes production,BMR, protein
synthesis

20. Electrolyte
& water
balance
Reabsorption of sodium in distal tubules, water retention,
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.

21. Epiphyseal plate closure: Mediated by estrogen
Testosterone → estrogen via aromatase
In testes, Sertoli cells express aromatase enzyme

22. Mechanism of action
Testosterone binds to an
intracellular receptor;Ex: NR3C4
Facilitating transcription of
various genes.
1: Negative Gonadotropin regulation
2: Wolffian duct stimulation :
sexual differentiation
Sexual maturation at puberty
Spermatogenesis ;gene regulation
3: External Virilization:
sexual differentiation ;Gene regulation

23. Genomic and non-genomic effects of testosterone.
Unbound bioactive testosterone interacts with the cytoplasmic
androgen receptor (AR).
AR is also activated by dihydrotestosterone in a similar way.
Ligand binding induces conformational changes of the receptor.
T-AR complex forms dimers and acts as a functional
transcription factor. Activated AR recognizes the androgen
response element in the nucleus due its specific structure.
Coactivators (CA) and RNA polymerase II are recruited for
transcription initiation.
Gene expression produces a pool of specific proteins that can
affect cell characteristics, metabolism and activity. The non-
genomic response is mediated via receptor-tyrosine-kinases
(RTK) or G-protein coupled receptors.
Subsequently, downstream signaling cascades are activated, that
can result in genomic effect (activation of various transcription
factors, protein activation or new protein synthesis).
G-protein coupled receptors can activate phospholipase C and
cause an increase of intracellular Ca 2+ . All these processes are
linked with changes in cell activity.

24. Degradation and Excretion of Testosterone
Conjugated either to Glucuronides or Sulfates
Conjugated metabolites are excreted
 From Gut through liver bile
 Or Kidneys through urine.

25. Testosterone
Regulation

26. Human Chorionic Gonadotropins:hCG
Fetal life:
Secreted by placenta
Stimulates testosterone secretion by the fetal testes
Testosterone is helps in formation of male genital organs in fetus.

27. Inhibin
• Glycoprotein
• Molecular weight : 10k-30k
• From Sertoli cells in males & granulosa cells in females
Action:
 Potent inhibitory feedback effect  Ant pituitary gland (FSH)
 Important Negative feedback mechanism  control of
spermatogenesis

28.  Heterodimers stimulates FSH
 Details not known
 Found in brain, bone marrow & other tissues
 Actions:
 In Bone marrow helps WBCs development.
 In embryonic life;involved in mesoderm formation.
Activins:

29. Follistatin:
A Pituitary autocrine glycoprotein
Inhibits secretion of FSH
Kisspeptins:
Family of neuropeptides localized ; Arcuate nucleus (brain)
Stimulators of GnRh secretion.
GnIH:
Upstream of GnRh
Operates at the testes: autocrine regulators of steroidogenesis

30. Primary
Hypogonadism
Secondary
Hypogonadism
Site Testes Pituitary gland,
hypothalamus
Serum Testosterone Decreased Decreased
FSH & LH Increased No changes, or
decreased
Causes Klinefelter’s
syndrome
Kallman’s
syndrome

31. Hypogonadism : Nonfunctional testes
During male fetal life:No male characteristics develop
Instead female sex organs formed.
Before puberty : Eunuchism :Infantile sex organs
Sex characters with tall height.
Castrated after puberty:
 Secondary sexual character not affected
 Decreased sex desire,impotence & sterility
 Gradual dysfnction of accessary sexual organs
 FSh & Lh increased due to negative feedback mechanism

32. Adiposgenital dystrophy syndrome (Frohlich’s syndrome )
 Rare disorder
 Characterized by: decreased GnRH production
 Obesity, Mental ,growth and genital organ retardation
 Associated with tumors of hypothalamus
 or hypothalamic eunchism develop

33. 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
Primary: prepubertal onset:Eunuchoidism

34. Hypogonadotropic Hypogonadism :
Kallmann’s syndrome
 Delayed puberty development ,micropenis,maldescended testes,
renal agenesis
 Cleft lip and palate ,oligodontia, digit malformation
 Corpus callosum agenesis
Secondary: prepubertal onset

35. Causes:
Infection: Mumps orchitis , radiations
Trauma
Bilateral orchiectomy
Autoimmune damage
Chronic diseases: Cirrhosis of liver
HIV
Signs and symptoms:
Loss of libido,Impotence,Infertility
Hypogonadotropic Hypogonadism
Ex: Kallmann’s syndrome
Primary post pubertal onset:

36. Post Pubertal onset
Infection : Mumps orchitis
Radiation
Trauma, Tumors
Bilateral orchiectomy
Chronic diseases: cirrhosis ,HIV,
Loss of libido
Impotence
Infertility

37. Klinefelter’s syndrome
Kallmann's syndrome