4. The Gonads

What are the main classes of sex hormones and their key examples?

• Androgens → Testosterone

• Oestrogens → 17β-Oestradiol

• Progestogens → Progesterone

What are the functions of the testes & the pathway of sperm production?

• Functions:

  • Spermatogenesis (sperm cell development)

  • Testosterone production

• Sperm production pathway:

  • Occurs in seminiferous tubules

  • Spermatozoa secreted into tubule lumen → epididymis → vas deferens → expelled from testes

How is testosterone secretion regulated & what is its role in spermatogenesis?

• Leydig cells (in testes) secrete testosterone

• Stimulated by LH & FSH from anterior pituitary

• LH → maintains spermatogenesis

• FSH → initiates spermatogenesis

• GnRH (from hypothalamus) controls LH & FSH via pulsatile release

• Sertoli cells (in tubule walls) aid sperm maturation & secrete inhibin

• Inhibin → negative feedback on FSH

• Testosterone → essential for spermatozoa maturation

• ↑ Testosterone → negative feedback on:

  • Hypothalamus = ↓ GnRH

  • Anterior pituitary = ↓ LH & FSH
    = ↓ testosterone from gonads

What is the mechanism of action of testosterone & the role of DHT?

• Testosterone enters cell, binds androgen receptor

• Complex binds DNA → protein production → cell response

• In some tissues, testosterone → DHT via 5α-reductase

• DHT = more potent; needed for full androgen effect

• 5α-reductase inhibitors ↓ DHT (used in treatment)

• Enzyme dysfunction → ↓ DHT → hyposecretion effects

What are the main actions of testosterone at different life stages?

• Foetus:

  • Male genitalia development

  • Testes descent

• Puberty:

  • Growth of sex organs

  • Growth spurt & bone epiphysis fusion

  • Deep voice, body hair, acne

  • ↑ Muscle & strength (anabolic)

• Adult:

  • Maintains masculinity, libido, spermatogenesis

  • Causes scalp recession & baldness

What are the causes & treatment of testosterone hyposecretion?

• Causes:

  • Absent testes at birth (primary hypogonadism)

  • Low pituitary gonadotrophins (secondary hypogonadism)

  • Undescended testes

  • Testes loss (castration/disease)

  • 5α-reductase deficiency

• Treatment:

  • Androgen replacement therapy

What are the methods of testosterone replacement therapy & which is most common?

• Deep IM injection: testosterone enantate or propionate

• Capsules (oily solution): testosterone undecanoate

• Transdermal (most common): Testim, Testogel, Tostran

What causes hypersecretion of testosterone & what is its effect?

• Cause: Rare, usually Leydig cell tumours in children

• Effect: Precocious puberty

What are the clinical uses of androgens?

• Replacement therapy for hypogonadism (testicular or pituitary disease)

• ↑ Muscle mass after chronic/wasting disease (e.g. nandrolone)

• Treatment of oestrogen-dependent tumours (e.g. some breast & cervical cancers)

  • May cause masculinisation in women (facial hair, voice deepening, acne

What are the clinical uses of anti-androgen treatments?

• Testosterone receptor antagonists:

  • Suppress excessive sexual drive

  • Treat acne/hirsutism (e.g. cyproterone acetate, flutamide)

• Androgen-dependent prostate cancer:

  • Use bicalutamide

• Benign prostatic hyperplasia (BPH):

  • Use finasteride (5α-reductase inhibitor) to reduce potent testosterone’s effect on prostate enlargement

How is the secretion of female sex hormones regulated, and what is the feedback mechanism?

• Ovaries secrete oestrogen (17β-estradiol) & progesterone

• Oestrogen & inhibin secretion is regulated by LH & FSH from the anterior pituitary

• LH & FSH are stimulated by GnRH from the hypothalamus

• Granulosa cells secrete inhibin → inhibits FSH

• Oestrogen exerts:

  • Direct negative feedback on LH

  • Indirect negative feedback on GnRH

• High oestrogen levels → ↓ GnRH → ↓ LH & FSH

• During ovulation: feedback switches to positive, causing LH/FSH surge → triggers ovulation

What happens during the ovarian cycle?

• Day 1: 10–20 follicles grow; 1 becomes dominant by day 6

• Dominant follicle matures into Graafian follicle, secretes oestrogen

• Day 14: Ovulation — oocyte released into fallopian tube

• Remaining cells form corpus luteum → secretes oestrogen & progesterone

• If no fertilisation → corpus luteum degenerates, cycle restarts

How do hormones regulate the ovarian & menstrual cycle?

• Days 1–13:

  • FSH ↑ → follicle maturation

  • Oestrogen ↑ from growing follicle → initially negative feedback

• Around Day 14:

  • High oestrogen switches to positive feedback

  • LH & FSH surge → ovulation

• Post-ovulation:

  • Follicle becomes corpus luteum → secretes oestrogen & progesterone

  • Progesterone ↑ → stabilises & vascularises endometrium

• If no fertilisation:

  • Corpus luteum degenerates → hormone levels ↓

  • Endometrium sheds → menstruation

  • Cycle restarts

What hormonal changes occur during pregnancy?

• hCG secreted from day 20 → basis of pregnancy tests

• hCG maintains corpus luteum for ~9 weeks → prevents ovulation & menstruation

• From 9 weeks, placenta secretes oestrogen, progesterone & hCG

• Corpus luteum regresses after placental takeover

What happens during menopause?

• Menstruation ceases (age 45–55)

• Symptoms:

  • Hot flushes

  • Sweating

  • Palpitations

  • ↑ Irritability, anxiety, depression

  • Vaginal atrophy

  • Osteoporosis

What are the principal actions of oestrogens?

• Essential for normal development/maintenance of female genital tract & breasts

• During puberty:

  • Stimulate growth of uterus, breast & vagina

  • Contribute to growth spurt & secondary sexual characteristics

What are the principal actions of oestrogens in adults?

• Regulate menstrual cycle (growth of endometrial lining)

• Important during pregnancy & lactation

• Maintain sexual drive & female personality

What are the principal actions of progestogens?

• Cause endometrial secretory changes for pregnancy

• Stimulate breast development for lactation

• Thicken & acidify cervical mucus (↓ sperm receptivity)

• Reduce spontaneous myometrial contractions during pregnancy

What are the effects of oestrogen hyposecretion?

• Primary hypogonadism: Ovarian failure (e.g. Turner’s) → no puberty, menstruation, or bone closure

• Secondary hypogonadism: Pituitary/hypothalamic issues → ↓ hormone signals, delayed development

What are the effects of oestrogen hypersecretion?

Ovarian tumours → irregular endometrial bleeding

What are the clinical uses of oestrogens?

• Treatment of hypogonadism

• Treatment of menopausal symptoms (e.g., surgical removal of ovaries, hysterectomy, severe endometriosis)

• Treatment of osteoporosis

What are the main formulations of HRT?

• Oral tablets (natural oestrogen)

• Transdermal patches

• Implants

• Vaginal cream or pessaries

What are less common clinical uses of oestrogens?

• Treatment of androgen-dependent prostate cancer

• Emergency contraception (now withdrawn due to side effects: nausea, vomiting, headaches)

What are less common clinical uses of oestrogens?

• Treatment of androgen-dependent prostate cancer

• Emergency contraception (now withdrawn due to side effects: nausea, vomiting, headaches)

What are clinical uses of oestrogens & anti-oestrogens?

• Treat infertility: clomiphene (risk of hyperovulation & multiple pregnancies)

• Treat oestrogen-dependent breast cancers:

  • Oestrogen antagonists: tamoxifen, toremifene

  • Aromatase inhibitors: letrozole, anastrozole

  • 3β-HSD inhibitor: trilostane

What are clinical uses of oestrogens & anti-oestrogens?

• Treat infertility: clomiphene (risk of hyperovulation & multiple pregnancies)

• Treat oestrogen-dependent breast cancers:

  • Oestrogen antagonists: tamoxifen, toremifene

  • Aromatase inhibitors: letrozole, anastrozole

  • 3β-HSD inhibitor: trilostane

What are clinical uses of progestogens?

• Control uterine bleeding & menstrual disturbances

• Treat endometriosis

• Examples: northisterone, norgestrel, levonorgestrel, dydrogesterone, medroxyprogesterone