Male Reproductive Hormones

Structure of the Testis
1. Seminiferous Tubule
  1. Main structural unit
  2. Each tubule ~60cm but tightly coiled
  3. Made of Sertoli cells and germ cells (spermatogonia)
    1. 600 million germ cells per testis during puberty
    2. Germ cells migrate from the basement membrane to the tubule lumen, developing into sperm as they go
      1. Spermatogonium
        Primary spermatocyte
        Mitosis
        Early spermatids
        Late spermatids
      2. Sertoli cells engulf remaining cytoplasm from late spermatids as they leave - leaves residual bodies
  4. Leydig cells lie between the tubules
2. Blood-testis barrier
  1. Formed by tight junctions between Sertoli cells
  2. Maintains internal environment of testis
    1. Keeps high concentration of hormones
    2. Protects against toxins
  3. Breaching of the barrier can cause infertility
    1. Autoimmunity against sperm components
Function of the Testis
1. Spermatogenesis
2. Production of male sex hormones - androgens
Androgen Production
1. Steroidogenesis takes place in Leydig cells
2. Main androgen is testosterone
  1. Testosterone production
    1. Cholesterol
      1. Pregnenolone (via cholesterol-side chain cleavage by P450scc)
        Progesterone (via 3-beta-hydroxysteroid dehydrogenase)
        17-alpha-OH-progesterone (via 17-alpha-hydolyase)
        Androstenedione (via 17, 20 lyase)
        Testosterone
        Oestradiol (via CYP19 aromatase)
        17-alpha-OH-pregnenolone (via 17-alpha-hydroxylase)
        DHEA (via 17,20 lyase)
        Androstenedione (via 3-bet-hydroxysteroid dehydrogenase)
        (via 17-beta-hydroxysteroid dehydrogenase)
        5-alpha-dihydrotestosterone - 5alphaDHT (via 5-alpha-reductase)
        Converted in peripheral tissues
        Exerts many of the hormonal actions of testosterone
        17-alpha-OH-progesterone (3-beta-hydroxysteroid dehydrogenase)
    2. Under hormonal control by the hypothalamo-pituitary-testicular axis
  2. Acts as a paracrine regulator of spermatogenesis (non-genomic action)
  3. Acts as a hormone and hormone precursor
Hormonal Control of Testicular Function
1. Controlled by the hypothalamo-pituitary-testicular axis
2. Gonadotrophin releasing hormone (GnRH) released by the hypothalamus in a pulsatile way
  1. Stimulates release of LH and FSH (only if pulsatile)
    1. LH (luteinising hormone) regulates Leydig cell function
      1. Testosterone is released
        Acts on Sertoli cells
        Spermatogenesis
        Hormone functions
        Inhibits LH and GnRH - negative feedback
    2. FSH (follicle stimulating hormone) regulates Sertoli cell function
      1. Sertoli cell inhibits FSH
      2. Spermatogenesis
    3. Spermatogenesis occurs at a low rate in the absence of FSH
3. Spermatogenesis is totally dependent on the high intra-testicular testosterone level
  1. Sertoli cells produce an androgen binding protein which retains testosterone in the testicular fluid
Actions of LH
1. AC binds to sigma region of LH, converting ATP to cAMP
  1. Activation of Protein kinase A
    1. Activation of StAR (steriodigenic acute regulatory protein)
      1. Delivers free cholesterol to P450scc (cholesterol side-chain cleavage enzyme)
        Testosterone production
    2. Increased cholesterol ester hydrolase
      1. Increased cholesterol ester
        Increased free cholesterol
    3. Nuclear effects - increased CYP (cytochrome P450) gene expression
Androgens in Blood
1. Diurnal variation - testosterone is highest in the morning
2. Circulates are bound to sex-hormone binding globulin (SHBG)
  1. Only 2% are unbound
3. Converted to DHT or oestradiol
4. Act through the androgen receptor - binds DHT and testosterone with equal affinity
  1. Bound receptor binds to androgen response element on DNA with co-activators and initiates transcription
  2. Androgen Receptor
    1. Gene is located on the X-chromosome
      1. Mutations are X-linked - mother has 50% chance of passing it onto a son
    2. Androgen insensitivity syndrome is a spectrum of disorders affecting men
Androgen Action in Men
1. Intra-uterine
  1. Development of male phenotype
  2. Development of penis, scrotum, prostate etc.
  3. Testicular descent into scrotum
    1. Before descent, testicles are suspended near kidneys by cranial suspensory ligaments
      1. Gubernaculum connects skin to epididymis
      2. Ligament degrades once testis descend and gubernaculum connects skin to testis
        Inguinal canal contains the vas deferens
  4. Programming of male behaviour
2. Puberty
  1. Development of male secondary sex characteristics
  2. Hypertrophy of larynx
  3. Development of seminal vesicles, prostate and initiation of sperm production
  4. Increased muscle mass
  5. Increased skin thickness and sebum formation
  6. Development of pubic and axillary hair
  7. Fusion of epiphyseal plates in long bones
3. Adults
  1. Reproductive effects - maintenance of spermatogenesis, secondary sex characteristics (beard growth), libido and feedback inhibition of GnRH secretion
  2. Metabolic effects - increasing circulating LDL/VLDL and decreasing HDL, increasing metabolic rate, red blood cell number, muscle mass and bone density
  3. Symptoms of deficiency
    1. Depression, fatigue, loss of libido
    2. Little facial hair growth, scant body hair
    3. Muscle weakness, loss of muscle definition
    4. Small testicles
4. Anabolic Androgen Steroid Abuse
  1. Increased aggression - road rage
  2. Increased muscle mass
  3. Acne
  4. Testicular atrophy and/or infertility
  5. Liver cancer (if taken orally)
Oestrogens in Men
1. Oestradiol mediates many of the actions of testosterone
  1. Negative feedback at the hypothalamus and pituitary, effects on the brain including libido and effects on the bone
2. Aromatose is highly expressed in adipose tissue - fat men are more feminine
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Male Reproductive Hormones

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	Created by maisie_oj about 11 years ago