Male hormones and reproduction Flashcards
What is the bio-synthetic precursor for all steroid hormones?
Cholesterol
Describe the pathway for progesterone
Acetate -> cholesterol -> pregnenolone -> progesterone
What are 3 androgens?
- Androstenedione
- Testosterone
- Dihydrotestosterone (DHT)
Describe the pathway for DHT
Acetate -> cholesterol -> pregnenolone -> progesterone -> Androstenedione -> Testosterone -> DHT
What are 2 oestrogens?
- estrone
- 17beta-estradiol
What is estrone converted from?
Androstenedione –> estrone (by aromatase)
What is 17beta-estradiol converted from?
Testosterone –> 17beta-estradiol (by aromatase)
What 2 hormones are needed for male reproductive function?
Estrogens and Progesterone
When is the progesterone level the same in males and females?
During the non-luteal phase
progesterone levels rise in the luteal phase
What is spermiogenesis?
Production of mature, motile spermatozoa
Name 5 parts of the male reproductive tract
- Testis
- Epidiymis
- Ductus deferens
- Accessory glands
- Urethra
What is the function of the Testis?
Sperm production, steroid hormone production
What is the function of the epididymis?
Sperm collection and maturation
What is the function of the ductus deferens?
Transport and storage
What is the function of the accessory glands?
Contributions to seminal fluid
What is the function of the urethra?
transport
Specifically, where is sperm produced?
In the seminiferous tubules of the testis
As sperm cells mature where do they move?
They move inwards towards the lumen
What cells are important during the movement of sperm to the epididymis ?
Myoid cells
Where does the biosynthesis of testosterone occur?
Mostly in Leydig cells
How is testosterone converted into DHT?
catalysed by 5alpha-reductase and NADPH
Where is testosterone converted into DHT?
Conversion takes place in the Sertoli cell
What is the most active androgen?
DHT
What family of receptors do receptors for all major classes of steroid hormone belong to?
Nuclear receptor superfamily
What are the features of the receptors in the nuclear receptor superfamily?
- They are proteins with 2 binding sites; one for steroid and the other for DNA
What happens when a steroidal ligand binds to receptor?
- produces a complex that acts on DNA
- the complex then acts on DNA and alters the repertoire of genes being expressed by target cells
- THIS activity defines the steroid receptors as transcription factors
What do androgens interact with?
Androgen receptors (AR)
What cell populations express AR?
- All major cell populations in the testis, epididymis and accessory glands
- Also found in tissues where secondary sexual characteristics appear
Why is androgen-AR binding necessary?
The various cell types require androgen-AR binding to fulfil their respective roles in sperm production, transport and activation
What are androgens responsible for?
The development of secondary sex characteristics (genital enlargement, sperm growth and maturation etc), anabolic effects and spermatogenesis
What controls sex steroid production?
Gonadotrophins (LH and FSH) - both expressed in male at constant levels
Where are the gonadotrophins secreted from?
Anterior pituitary
What causes the secretion of gonadotrophins?
The secretion of gonadotrophin releasing hormone (GnRH) from the Hypothalamus
- pulsatile release, constant frequency
What do the sex steroids control?
Sperm production (ejaculate) and maturation
What is produced in the testis?
- spermatozoa
- sex steroids
How do gonadotrophins enter cells?
By binding to receptors on the cell surface (polypeptide hormones can’t pass cell membrane - hydrophillic)
Where does FSH bind ?
To the FSH receptor on the surface of a sertoli cell
Where does LH bind?
To the LH receptor on the surface of the Leydig cell
Where is Testosterone transported once it is produced in the leydig cell?
To the sertoli cell
What is produced in the sertoli cell?
Androgen-binding protein (ABP)
What does ABP bind to?
Binds to testosterone and DHT and concentrates them in the luminal fluid of the seminiferous tubules and downstream regions of the male tract and is released as a complex by the sertoli cell
What does the release of a ABP-steroid complex from the sertoli cell stimulate?
- spermatogenesis in the seminiferous tubules,
- sperm maturation in the epididymis
- accessory gland secretions
- myoid cell contractile activity to propel sperm along the tract
What else happens in the sertoli cell?
5-alpha reductase converts T to DHT
Where do complex’s travel to once they have left the sertoli cell?
To the epididymis
What feedback is included for testosterone?
purely negative feedback: testosterone and inhibin inhibit the secretion of GnRH by the hypothalamus and LH and FSH by the pituitary
What are sperm maturation stages dependent on?
Androgen-dependent (Sertoli cell nurse function)
What is required to move released sperm along the seminiferous tubule?
Myoid cell contractility. They are AR-positive, action is androgen-dependent
How do sperm exit the sertoli cell?
Tail first and move towards lumen (not yet motile!!)
Where is the ability to swim initially acquired for sperm?
In the epididymis (DHT-dependent) with futher FULL activation in the female tract
When does spermeogenesis occur?
Post meiosis
What is the normal volume of ejaculate?
1.5-5.0 ml
What is included in the composition of the ejaculate?
- Epididymis & Ductus deferens (sperm-rich fraction): 5% of the ejaculate volume
- Prostatic secretion: 13-33% of the ejaculate volume
- Seminal vesicle secretion: 46 – 80% of the ejaculate volume
- Bulbo-urethral gland secretion: 5% of the ejaculate
What is erection?
erectile tissue [corpus cavernosum and corpus spongiosum] becomes engorged with blood, arterioles dilated as a result of parasympathetic nervous system activity
What are emission and ejaculation controlled by?
Sympathetic nervous system
What is erectile dysfunction?
- Pathological bases – psychogenic; neurogenic; vascular and endocrine
- Latrogenic causes of impotence – many drugs including tricyclics and SSRIs ; antihypertensives including beta blockers and calcium antagonists
How is erectile dysfunction managed?
- PGE1 – alprostadil
- PDE5 inhibitors – eg sildenafil (inhibits the breakdown of cAMP)
What are the risk factors for prostate cancer?
- age
- ethnicity
- family history
What are the symptoms of prostate cancer?
- Urgent and frequent urination
- Nocturnal enuresis (involuntary urination)
- Difficulty starting or emptying the bladder
- Urine flow weak, interrupted or difficult to control
- Back or pelvic pain
What is included in the pharmacological management of prostate cancer?
- Gonadorelin (GnRH) agonists and antagonists
- Androgen antagonist – cyproterone acetate (effective provided keeps androgen dependency of normal prostate)
- 5-a-reductase inhibitors – dutasteride & finasteride (blocking DHT – more active)
What does exogenous Testosterone lead to?
Decreased LH and FSH and decreased fertility (used as contraception in males?? - would need very high doses as its difficult to completely inhibit sperm production)
These may lead to iatrogenic hypogonadotrophic hypogonadism
Testosterone undecanoate – longer acting depot, better PK (eg Nebido ™)
