List 3 processes which occur in the male reproducive system
- Gametogenesis
- Secretion of sex hormones (androgens, especially testosterone)
- Delivery of sperm to female tract
Name 2 processes that occur in the testis
- Sperm reproduction
- Hormone production
Describe the structure of the male reproductive system
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What is the vas deferens?
The duct which conveys sperm from the testicle to urethra
What are the seminiferous tubules?
- Found in testes
- Location of meiosis and the subsequent creation of male gametes (sperm)
Name 3 cells found in the testis
- Leydig cells (outside s. tubules)
- Sertoli cells (within s. tubules - epithelium)
- Germ cells (within s. tubules and lumen)
How are FSH & LH regulated by the hypothalamus and pituitary in males?
- GnRH secreted from hypothalamus
- GnRH stimulates secretion of FSH and LH
- FSH and LH produced by gonadotroph cells in the anterior pituitary
How does LH act in the testis?
- LH stimulates the Leydig cells within the testes/s.tubules
→ produces testosterone
- This encourages sperm production and leads to secondary sexual characteristics
What is the role of FSH in the testis?
- FSH stimulates primary spermatocytes to undergo the first division of meiosis
→ forming secondary spermatocytes
→ leading to the maturation of sperm cells
- Also acts on Sertoli cells = inhibin
How is FSH regulated by negative feedback?
- FSH causes the production of Inhibin
- Inhibin inhibits FSH production by having a negative feedback effect on the anterior pituitary
How is LH regulated by negative feedback?
- LH causes production of testosterone
- Testosterone has a negative feedback effect on the hypothalamus and anterior pituitary
→ inhibiting GnRH and so LH production
What are the effects of testosterone (androgens) before birth?
Testosterone is synthesised by fatal Leydig cells in response to maternal hCG
- It masculinises the external genitalia
- Promotes descent of testes into scrotum
What are the effects of testosterone (androgens) after birth?
- Testosterone production very low until puberty
- Around puberty, LH production by the pituitary is initiated
→ stimulates testosterone output by testis
What are the effects of testosterone on sex-specific tissues? (i.e. after puberty)
- At puberty, testosterone promotes growth and maturation of reproductive system
→ penis & scrotum enlargement
→ scrotum darkening
→ Enlargement of epididymis, prostate, seminal vesicles
- Essential for spermatogenisis
- Maintains reproductive tract throughout adulthood
List 2 reproductive effects of testosterone
- Development of sex drive (libido) at puberty
- Control of gonadotrophin secretion (via negative feedback)
List 5 effects of androgens on secondary sex characteristics
- Promotes muscle growth responsible for male body conformation (increases protein synthesis and lean:fat ratio, decreases protein degradation)
- Promotes bone growth at puberty then closure of epiphyses (ends of bone)
- Induces male pattern of hair growth (i.e. beard)
- Causes deepening of voice
- Skin and sebaceous glands thicken (acne)
What is the andropause?
- “male menopause”, age 48-70
- Decreased testosterone production
- Reduced testicular androgen response
- However sperm production continues (unlike menopause)
List 4 physical changes caused by the andropause
- Loss of muscle mass
- Shrinking of reproductive organs - penis, testis, accessory glands
- Loss of libido, increased stimulus needed for erection, longer refractory period
- Osteoporosis
List 2 mental changes caused by the andropause
- Depression
- Reduced energy
List 5 common psychological causes of erectile dysfunction
- Nervousness
- Guilt - adultery etc
- Relationship problems
- Depression
- Exhaustion
List up to 6 common physcial causes of ED
- Deterioration of arteries - common in older men, including those with high BP
- Diabetes
- Smoking
- Excessive alcohol
- Obese/out of condition
- Side effects of certain drugs - e.g. anti-hypertensives, anti-depressants
What are the 3 different regions of the erectile tissue?
1. & 2. Pair of parallel spongy columns = corpus cavernosum
3. Central corpus spongiosum enclosing urethra
What are the cavernous sinuses?
- Pool-shaped blood vessels
- Erectile tissue rich in cavernous sinuses
- Fill with blood during an erection
Summarise the process behind an erection
- Sympathetic and parasympathetic nerves innervate blood vessels and sinusoids in erectile tissue
- Psychogenic and/or tactile stimulation triggers:
- increased acetylcholine release (parasympathetic)
- increased nNOS release
- Decreased noradrenaline release (sympathetic)
- Leads to increased NO = dilation of smooth muscle of arterioles and sinusoids within erectile tissue
- Increase in blood flow in the corpus cavernosum and corpus spongiosum
- Erection
Describe the biochemical process of erection in detail
- ACh and nNOS (neuronal) are released from the cavernous nerve (in penis)
- This stimulates the production of eNOS (NO synthase) within the vascular endothelial cells
- NO is synthesised and diffuses into the surrounding vascular smooth muscle
- Once inside, NO binds to and activates guanylyl cyclase which converts GTP into the second messenger cGMP
- cGMP activates its dependent protein kinase - PKG
- PKG activation promotes vascular smooth muscle relaxation (to allow vasodilation) by:
- Hyperpolarisation (by opening K+ channels)
- Endoplasmic reticulum sequestration of Ca2+
- Inhibition of Ca2+ channels, stopping influx
- Free intracellular calcium binds to and activates calmodium (protein)
- Calmodium aids phosphorylation of myosin light chains (MLC)
→ MLCs = sub-units found on myosin heads - when phosphorylated they cross-bridge the mysoin heads and actin filaments = cellular contraction
- Therefore decrease in cytosolic calcium initiated by PKG results in vascular smooth muscle relaxation
→ ERECTION
What is the chemical name for viagra?
Sildenail citrate
What is the mechanism of action of Viagra?
- Sildenafil competitively inhibits phosphodiesterase type 5 (PDE5) = the enzyme responsible for the degradation of cGMP to GMP
- Stabilisation of cGMP = prolonged action of second messenger
- Therefore greater, more sustained dilation of sinusoidal smooth muscle via PKG-dependent reduction in free cystolic calcium ion concentration
- → Engorgement of erectile tissue with blood
List 4 common side effects of sildenafil citrate
- Flushing
- Headache
- Nasal congestion
- Stomach discomfort after meals
1, 2 & 3 due to the vasodilation necessary for mechanism of action
List 4 less common side effects of sildenafil citrate
- Blurred vision, loss of hearing
- Bladder pain
- DIzziness
- Pain on urination
What is Priapism?
Persistent, painful erection lasting longer than 4 hours
→ In absence of sexual stimulation/desire
What are the 2 types of Priapism?
- Ischemic (no-flow) - obstruction in venous drainage
- Non-ischemic (high-flow) - excess arterial supply
How should Priapism be treated?
- Medical attention should be sought immediately
- Delayed treatment (especially ischemic type) can cause damage to erectile tissue and irreversible ED
- Treatment may involve intracavernosal injection of α-adrenoceptor agonist (e.g. phenylephrine)
Name another use of Sildenafil
Treatment of pulmonary arterial hypertension (under name Revatio)
→ Reduces BP by widening blood vessels in the lungs
List 3 contra-indications of Viagra
- Low BP
- CV disease
- Recent stroke
What is the prostate gland?
- Walnut-sized muscular gland surrounding the urethra, just below the bladder
- Secretes (gland) milky alkaline prostatic fluid
- During orgasm, muscular contractions of prostate propel prostatic fluid into urethra
- Here it is mixed with sperm and secretions from other accessory glands
- = Ejaculation
What is Benign Prostatic Hyperplasia (BPH)
Enlargement of prostate - restricts urethra
Symptoms of BPH:
- Hesitant, interrupted, weak urine stream
- Urgency and leaking/dribbling
- More frequent urination, especially at night
- 50% of 60 year old men have BPH symptoms
How is BPH treated?
- Alpha-adrenoceptor blockers
- 5-alpha-reductase inhibtors
- Minimally invasive surgery
How do alpha-adrenoceptor blockers work to treat BPH?
- Relax muscle fibres within prostate - reducing obstruction to urine flow
- Do not reduce size of prostate
- e.g. tamsulosin, terasozin
- Occassional side effects - dizzines (postural hypotension), heache, drowsiness
Why should Viagra be used with caution in men talking alpha-adrenoceptor blockers?
The combination may increase the risk of fall in blood pressure
= dizziness, fainting
How do 5-alpha-reductase inhibitors work?
Inhibit the growth of the prostate and reduce size of gland
e.g. finasteride
List 4 risk factors for prostate cancer
- Age - risk increases with age, mostly in over 50s
- Family history - 2.5x more likely if father or brother has been diagnosed
- Ethnicity - Afro-Caribbeans 3x more likely to be diagnosed with prostate cancer than whites
- Diet - typical western diet increases risk (high in saturated animal fats and red meat)
What are the symptoms of prostate cancer?
Similar to BPH (in early stages):
- Hesitant, interrupted, weak urine stream
- Urgency and leaking/dribbling
- More frequent urination especially at night
How is prostate cancer diagnosed?
Tests by GP:
- Urine test to rule out infection
- Then blood test to measure PSA (Prostate Specific Antigen)
- DRE (Direct Rectal Examination)
Hospital tests:
- TRUS (Trans-Rectal Ultra Sound) guided biopsy
- CT scan
- MRI scan
- Bone scan with or without X-rays
What stages can prostate cancer be at?
- Localised (only affecting prostate)
- Locally advanced
- Advanced (metastasis - typically to bone)
How is Localised Prostate Cancer treated?
- Active surveillance - treatment started only if/when necessary
→ Radiotherapy
→ Surgical prostatectomy
How is Locally Advanced or Advanced PC treated?
- Hormone therapy
- Tumour growth often androgen-dependent so aim is to block androgen production or action
- Can also be achieved by surgical castration
How does hormone therapy work to treat locally advanced/advanced PC?
- Down-regulate GnRH receptors to block LH (and androgen) secretion
- Block androgen synthesis directly
- Block androgen receptors