Week 5 - Hormones and Reproduction - The Male

Question 1

Describe the anatomy of the male reproductive tract + the role for each part

Answer 1

1. Testis - produces sperm + steroid hormone e.g. testosterone
   - Leydig cells - produce testosterone + sperm
   - these cells surround sertoli cells
   - Sertoli cells - convert testosterone into DHT
   - also procude inhibin
2. Urethra - transport (how sperm leaves body)
3. Epididymis - site of sperm collection + maturation
   - mature sperm cell occur due to myotic cell division
   - is site where immature sperm cell become mobile / gain ability to swim
4. Vas Deferens - sperm storage + transport

Human sperm has a lot of variability + irregular morphology compared to other mammals = human reproduction is difficult

Question 2

What are the male reproductive hormones

Answer 2

Androgens = sex steroid hormones
- inc. testosterone, dihydrotestosterone (DHT)
- DHT is the active form of testosterone (is more potent)
Males also have progesterone + oestrogen (sustain production of mature, motile sperm)

Question 3

How are the sex steroid hormones (adrogens) synthesised

Adrogens - testosterone and DHT (dihydrotestosterone)

Answer 3

1. Start with cholesterol (occurs in leydig cells)
   
   • cholesterol = starting material for ALL steroid hormones
2. Cholesterol → pregnenolone → progesterone → androstenedione → testosterone
3. Testosterone is reduced into DHT by 5α reductase (in sertoli cells)
   
   • DHT is more potent / active form

Androgens bind to adrogen receptor (AR) before cells fulfill their roles

Question 4

How is gonadal hormone production regulated (HPG axis)

Answer 4

HPG axis = Hypothalamus-Pituitary-Gonadal Axis
- this regulates production of sex steroids in men

1. Hypothalamus
   - releases Gonadatropin Releasing hormone (GnRH) from GnRH neurones
   - GnRH acts on anterior pituitary
   - released in a pulsatile manner
2. Anterior Pituitary Gland
   - releases 2 gonadatropin hormones (FSH + LH)
   - FSH and LG enter blood stream + act on testis
   - gondatropin control sex steroid hormone production
3. Testis
   - produce sex steroids: testosterone, DHT and inhibin
   - sex steroids act on testis + control / regulate sperm production + maturation

Question 5

How does the feedback control work (hormone production)

Answer 5

If GnRH was screted non-stop = uncontrolled sperm + testosterone = not ideal

• ↑ in plasma testosterone will feedback to AR (androgen receptor) in hypothalmus + anterior pituitary gland
  - in hypothalamus = stop GnRH release
  - in anterior pituitary = stop FSH and LH release
• inhibin feedback to a.pituitary to stop secreting FSH

Question 6

List the 2 male reproductive disorders

Answer 6

1. Male infetrility / Subfertility
2. Prostate cancer

Question 7

What is Male infertility / subfertility

Inc. Cause and Normal sperm parameters

Answer 7

When the sperm conc. is below the required amount to achieve successful pregnancy
- problems can be daignosed after 6 successive menstural cycles

CAUSE:
- linked to problems with production e.g. low numbers, poor quality (morphology), motility etc.
- Infection
- Ejaculation problems
- Hormonal imbalance
- Health and lifestyle
- poor diet, inactivity, obesity, smoking etc. causing steady decline in sperm count

Normal sperm parameters:
- volume ≥ 1.5ml
- motility ≥ 40%
- sperm conc. ≥ 15x 10⁶/ml
- output 39 x 10⁶ per ejaculate

Question 8

What are the therapeutics for male infertility

Answer 8

• Lifestyle modification
  
  • inc. smoking cessation, weight loss, ↓ alcohol intake
• Treatment of infections
• Treatment of ejaculation disorders
• Assisted Reproductive Technology (ART)
  - e.g. IVF, ISI

Question 9

What is prostate cancer

Inc. 4 risk factors, symptoms, incidence and mortality

Answer 9

• Has a risk of 1 in 6 (2nd leading cancer death in males after lung)

RISK FACTORS:
- Family history
- Ethnicity (more common in african / carrbinean)
- Age (older = ↑ risk)
- Obesity

SYMPTOMS:
- urgent + frequent urination
- Difficulty starting / emptying bladder
- Involuntary urination at night
- Urine flow weak, interrupted or difficult to control
- Back or pelvic pain

Question 10

What are the therapeutics for Prostate cancer

Answer 10

Prostate cancer can be worsened by androgen action (e.g. testosterone) on prostate gland
- ALL PHARMACOLOGICAL treatment is based on ↓ testosterone production / action

1. Anti-andgrogen therapy
   - drug blocks AR (androgen receptor)
2. LH blockade
   - drug blocks production of LH = reduced testosterone produced
3. GnRH agonist
   - continued use leads to down-regulation (negative feedback) = ↓ FSH and LH
4. 5α-reductase inihibitors
   - inihibt conversion of testosterone into DHT
   - ↓ potent form produced = ↓ effect of androgem on prostate

Question 11

What are the available male contraception

Answer 11

AIM: to inihbit sperm production to a level where it will inihbit fertility / won’t cause pregnancy

OPTIONS:
1. Progestin and Testoserone gel (combined)
- combo supresses sperm production
- combo allows a lower dose of testoserone to be used = ↓ risk of gonads shrinking
- effective + reversible supression of testis
- currently going through trials