1. CORE OVERVIEW (BIG PICTURE LOGIC)

Dual function of male gonads

• Gamete production → Spermatogenesis
• Hormone secretion → Androgens (mainly testosterone)

Key contrasts with female system

• Gonadotropin secretion is non-cyclical
• Reproductive capacity persists lifelong
• Function declines slowly with age, not abruptly (no menopause equivalent)

2. STRUCTURE OF THE MALE REPRODUCTIVE SYSTEM

Testes: internal architecture

• Composed of loops of seminiferous tubules
• Function:
• Spermatogenesis occurs in tubule walls
• Tubules drain → rete testis → epididymis (head → body → tail)

Sperm pathway (exam favorite)

Seminiferous tubules
→ Rete testis
→ Epididymis (head → tail)
→ Vas deferens
→ Ejaculatory duct
→ Prostatic urethra
→ External urethra

Interstitial (Leydig) cells

• Located between seminiferous tubules
• Contain lipid granules
• Secrete testosterone into bloodstream

Spermatic circulation & countercurrent exchange

• Spermatic artery: tortuous
• Pampiniform plexus veins: surround artery
• Blood flows in opposite directions
• Enables:
• Heat exchange (cooling testes)
• Possible testosterone exchange
• Same principle as renal countercurrent exchange

3. BLOOD–TESTIS BARRIER (CRITICAL CONCEPT)

Structural basis

• Tight junctions between Sertoli cells
• Divide tubule into:
• Basal compartment (spermatogonia)
• Adluminal compartment (meiotic & post-meiotic cells)

Functions (WHY IT EXISTS)

1. Protects germ cells from toxins
2. Prevents autoimmune reaction
• Germ cells express novel antigens
3. Maintains unique tubular fluid composition
4. Facilitates osmotic fluid movement

What crosses the barrier?

• Steroid hormones → freely
• Some paracrine proteins
• Germ cells migrate across via:
• Coordinated breakdown & re-formation of tight junctions
• Barrier integrity maintained throughout

Seminiferous tubular fluid composition

• Low: protein, glucose
• High:
• Androgens
• Estrogens
• K⁺
• Inositol
• Glutamic & aspartic acids

4. SPERMATOGENESIS (STEP-BY-STEP LOGIC)

Timeline

• Begins at puberty
• Total duration ≈ 74 days

Cellular sequence

Spermatogonia (diploid, basal lamina)
→ Primary spermatocytes
→ Meiosis I
→ Secondary spermatocytes(adluminal compartment)
→ Meiosis II
→ Spermatids (haploid, 23 chromosomes)
→ Spermatozoa

Cytoplasmic bridges (exam favorite WHY)

• Daughter cells remain connected
• Ensures:
• Synchronous maturation
• Uniform gene expression
• One spermatogonium → ~512 spermatids

5. SPERM STRUCTURE & MOLECULAR SPECIALTIES

Sperm head

• Packed with DNA
• Covered by acrosome
• Enzyme-rich (lysosome-like)
• Required for ovum penetration

Sperm tail

• Proximal segment wrapped by mitochondrial sheath(middle piece)
• Provides ATP for motility

Germinal ACE (gACE)

• Small ACE isoform
• Derived from same gene as somatic ACE
• Tissue-specific expression (alternate splicing)
• Knockout → infertility
• Exact function still unclear

6. ROLE OF SERTOLI CELLS (CENTRAL CONTROLLERS)

What Sertoli cells do

• Structural support for germ cells
• Form blood–testis barrier
• Secrete:
• Androgen-binding protein (ABP)
• Inhibin
• MIS
• Express aromatase (CYP19) → produce estrogens

Hormonal control logic

• FSH → Sertoli cells
• Promotes spermatid → spermatozoa maturation
• Increases ABP production
• Testosterone (via LH):
• Required for late spermiogenesis
• Acts on Sertoli cells (not directly on germ cells)

Key insight

• Early spermatogenic stages → androgen-independent
• Final maturation → androgen-dependent

7. RETE TESTIS & ESTROGEN ROLE (HIGH-YIELD DETAIL)

• Rete testis fluid is estrogen-rich
• Walls contain ER-α receptors
• Function:
• Reabsorption of fluid
• Concentration of sperm
• Failure → diluted sperm → ↓ fertility

8. EPIDIDYMAL MATURATION OF SPERM

What changes in epididymis?

• Sperm acquire:
• Motility
• Progressive forward movement

CatSper channels (VERY EXAM-FAVORITE)

• Located in principal piece of tail
• pH-sensitive Ca²⁺ channels
• Activated when sperm move to alkaline:
• Vagina (pH ~5) → Cervix (pH ~8)
• CatSper knockout → infertility

Chemotaxis

• Sperm express olfactory receptors
• Ovaries release odorant-like molecules
• Helps guide sperm toward ovum

9. EJACULATION & CAPACITATION

Ejaculation control

• Vas deferens contraction mediated partly by P2X ATP-gated receptors
• Knockout → ↓ fertility

Capacitation (in female tract)

• Occurs mainly in uterine tube isthmus
• Effects:
• ↑ Motility
• Prepares for acrosome reaction
• Facilitatory, not mandatory (IVF possible without it)

10. TEMPERATURE & SPERM PRODUCTION

Optimal temperature

• Testes: ~32°C
• Lower than core body temperature

Cooling mechanisms

• Scrotal exposure
• Countercurrent heat exchange

Clinical relevance

• Cryptorchidism → sterility
• Heat exposure (hot baths, tight supporters):
• ↓ sperm count up to 90%
• Not reliable contraception
• Seasonal variation:
• Higher sperm counts in winter

11. SEMEN: COMPOSITION & SIGNIFICANCE

Semen volume

• 2.5–3.5 mL per ejaculation
• Decreases with repeated ejaculation

Sperm count logic

• Normal: ~100 million/mL
• Infertility risk:
• 20–40 million/mL → 50% infertile
• <20 million/mL → nearly all infertile
• Abnormal morphology/motility also important

Gland contributions

• Seminal vesicles → 60%
• Prostate → 20%
• Others: Cowper, urethral glands

Semen contents (exam table logic)

• Fructose
• Prostaglandins
• Zinc
• PSA
• Buffers
• Fibrinolysin
• Citric acid

12. ERECTION: NEUROVASCULAR LOGIC

Initiation

• Parasympathetic (pelvic splanchnic nerves)
• Neurotransmitters:
• ACh
• VIP
• Nitric oxide (NO)

NO–cGMP pathway

• NO → guanylyl cyclase → ↑ cGMP
• cGMP → vasodilation → erection

PDE-5 inhibitors

• Sildenafil, tadalafil, vardenafil
• Prevent cGMP breakdown
• Side effect:
• PDE-6 inhibition → blue-green vision defect

Termination

• Sympathetic vasoconstriction

13. EJACULATION REFLEX (2-STAGE)

1. Emission

• Sympathetic (L1–L2)
• Via hypogastric nerves
• Smooth muscle contraction:
• Vas deferens
• Seminal vesicles
• internal urethral sphincter

2. Ejaculation proper

• Somatic reflex
• Bulbocavernosus muscle
• Sacral segments (S1–S3)
• Via pudendal nerve

14. PROSTATE-SPECIFIC ANTIGEN (PSA)

• 30 kDa serine protease
• Androgen-regulated gene
• Function:
• Liquefies semen (hydrolyzes semenogelin)
• Clinical:
• ↑ in prostate cancer
• Also ↑ in BPH, prostatitis
• Not cancer-specific

15. MALE CONTRACEPTION & VASECTOMY

Pharmacologic approaches

• Hormonal suppression
• CatSper inhibition
• Natural compounds
• All limited by:
• High sperm numbers
• Regeneration

Vasectomy

• Bilateral vas deferens ligation
• Highly effective
• ~50% develop anti-sperm antibodies
• Usually no systemic harm

Reversal

• Improved success
• ~50% pregnancy within 2 years

EXAM LOCK SUMMARY (ONE-LOOK RECALL)

• Blood–testis barrier → Sertoli tight junctions
• Spermatogenesis duration → 74 days
• Final spermiogenesis → Androgen + FSH dependent
• Motility acquisition → Epididymis + CatSper
• Erection mediator → NO → cGMP
• Ejaculation:
• Emission → Sympathetic
• Expulsion → Somatic
• PSA → Not cancer-specific

ENDOCRINE FUNCTION OF THE TESTES — LOGIC-BASED, ZERO-OMISSION NOTE (FULL CONCEPT COVER)

1) BIG PICTURE (WHY TESTIS IS ENDOCRINE)

Dual endocrine outputs

• Main hormone: Testosterone
• Also: small amounts of estrogens (via aromatization)

Core endocrine jobs of androgens

• Negative feedback on pituitary LH
• Male secondary sex characteristics (puberty changes)
• Protein anabolic / growth-promoting effects
• Maintain spermatogenesis (with FSH)

2) TESTOSTERONE — CHEMISTRY + SOURCE LOGIC

Chemistry (what kind of molecule)

• C19 steroid
• Has 17-hydroxyl (OH) group

Sources (where it comes from)

• Leydig cells synthesize it from cholesterol
• Also formed from androstenedione (from adrenal cortex) 17b-HSD
• need 17 beta OH dehydrogenase

Universal steroid logic (exam principle)

• Steroid pathways across endocrine organs are similar
• Organs differ mainly by which enzymes they have

3) BIOSYNTHESIS IN LEYDIG CELLS (ENZYME LOGIC)

Enzymes present vs absent (key differentiator from adrenal)

• Absent in Leydig: 11-hydroxylase and 21-hydroxylase (adrenal-type enzymes)
• Present in Leydig: 17α-hydroxylase

Main pathway described (dominant human route)

1. Cholesterol → Pregnenolone
2. Pregnenolone is 17-hydroxylated (because 17α-hydroxylase exists)
3. Then side-chain cleavage → forms DHEA (dehydroepiandrosterone)
4. DHEA → Androstenedione → Testosterone

Alternative pathway (mentioned but less prominent in humans)

• Androstenedione can also be formed via:
• Progesterone
• 17-hydroxyprogesterone
• But this route is less prominent in humans

4) CONTROL BY LH (SIGNALING MECHANISM)

Controller hormone

• LH controls testosterone secretion

Cellular mechanism (stepwise)

• LH binds LH receptor (GPCR)
• Couples to Gs
• → ↑ cAMP
• cAMP activates protein kinase A (PKA)
• PKA causes:
1. ↑ formation of free cholesterol from cholesterol esters
2. ↑ conversion cholesterol → pregnenolone

✅ So: LH → Gs → cAMP → PKA → cholesterol mobilization + steroidogenesis

5) SECRETION RATE (NUMBERS)

Adult male secretion rate

• 4–9 mg/day
• (13.9–31.33 μmol/day)

In females

• Females also secrete small amounts of testosterone
• Main source: ovary
• Possibly also: adrenal

6) TRANSPORT IN BLOOD (BOUND VS FREE)

% bound in plasma

• 98% protein bound

Binding distribution

• 65% to GBG / sex steroid–binding globulin (β-globulin)
• 33% to albumin

Extra point

• GBG also binds estradiol

7) PLASMA LEVELS (MALE VS FEMALE) + AGE TREND

Adult men

• Total (free + bound): 300–1000 ng/dL
• (10.4–34.7 nmol/L)
• Declines somewhat with age

Adult women

• 30–70 ng/dL
• (1.04–2.43 nmol/L)

8) METABOLISM + URINARY MARKERS (EXAM TRAPS INCLUDED)

What happens to circulating testosterone?

Minor pathway

• A small amount → converted to estradiol

Major pathway

• Most → converted to 17-ketosteroids
• Mainly androsterone
• and its isomer etiocholanolone
• Excreted in urine

Origin of urinary 17-ketosteroids

• ~2/3 adrenal origin
• ~1/3 testicular origin

Critical exam clarification (often asked)

• Most 17-ketosteroids are weak androgens
• potency ≤20% of testosterone
• But:
• Not all 17-ketosteroids are androgens
• Not all androgens are 17-ketosteroids
• Examples:
• Etiocholanolone: no androgenic activity
• Testosterone: NOT a 17-ketosteroid

9) ACTIONS OF TESTOSTERONE (CONCEPT MAP)

Core actions (after development phase too)

1. Negative feedback: inhibits pituitary LH
2. Secondary sex characteristics: puberty changes
3. Anabolic effect: ↑ protein synthesis, ↓ breakdown
4. Spermatogenesis support: with FSH

10) SECONDARY SEX CHARACTERISTICS (PUBERTY CHANGES — COMPLETE LIST)

External genitalia

• Penis increases length + width
• Scrotum becomes pigmented + rugose

Internal genitalia

• Seminal vesicles enlarge + secrete
• begin forming fructose
• fructose = main nutritional supply for sperm
• Prostate enlarges + secretes
• Bulbourethral glands enlarge + secrete

Voice

• Larynx enlarges
• Vocal cords lengthen + thicken
• Voice becomes deeper

Hair growth

• Beard appears
• Scalp hairline recedes anterolaterally
• Pubic hair male pattern: triangle with apex up
• Hair appears:
• axilla
• chest
• around anus
• General body hair increases
• Scalp hair decreases overall (androgens ↑ body hair but ↓ scalp hair)
• Hereditary baldness often needs DHT (may not develop without it)

Mental/behavioral

• More aggressive, active attitude
• Interest in opposite sex develops
• (Human psychological effects hard to define; in animals → boisterous/aggressive play)

Body conformation

• Shoulders broaden
• Muscles enlarge

Skin

• Sebaceous secretion thickens + increases → predisposes to acne

11) ANABOLIC EFFECTS (WHAT ANDROGENS DO TO BODY)

Protein effects

• ↑ protein synthesis
• ↓ protein breakdown
• → ↑ growth rate

Epiphyseal closure correction (important update)

• Previously thought: androgens close epiphyses
• Now: epiphyseal closure is due to estrogens

Electrolyte/water retention (secondary to anabolic effects)

• Moderate retention of:
• Na⁺, K⁺, H₂O
• Ca²⁺
• SO₄²⁻
• PO₄³⁻
• Also increase kidney size

Exogenous testosterone limitation

• Anabolic doses are also:
• Masculinizing
• increase libido
• Limits use for wasting diseases
• Attempts to separate anabolic from androgenic effects in synthetic steroids: not successful

12) MECHANISM OF ACTION (RECEPTOR + DHT AMPLIFICATION)

Steroid receptor mechanism

• Testosterone binds intracellular receptor
• Hormone–receptor complex → nucleus → binds DNA
• → alters gene transcription

Conversion to DHT (tissue-specific amplification)

• In some target cells: testosterone → DHT via 5α-reductase
• DHT binds same receptor as testosterone
• Plasma DHT ~ 10% of testosterone

Why DHT amplifies action

• Testosterone–receptor complex is less stable
• DHT–receptor complex:
• more stable
• fits DNA-binding state better
• So: DHT = amplifier in certain tissues

Two 5α-reductase isoenzymes (different genes)

• Type 1: skin throughout body; dominant enzyme in scalp
• Type 2: genital skin, prostate, other genital tissues

13) DEVELOPMENTAL ROLES: TESTOSTERONE VS DHT (VERY EXAM-FAVORITE)

During development

• Testosterone–receptor complexes:
• maturation of Wolffian ducts→ male internal genitalia
• DHT–receptor complexes:
• formation of male external genitalia

Puberty & specific tissue effects

• DHT mainly responsible for:
• prostate enlargement
• probably penis enlargement at puberty
• facial hair
• acne
• temporal recession of hairline
• Testosterone mainly responsible for:
• ↑ muscle mass
• male sex drive / libido

14) CLINICAL BOX: CONGENITAL 5α-REDUCTASE DEFICIENCY (TYPE 2 MUTATION)

What’s mutated

• Gene for type 2 5α-reductase

Where common

• Certain parts of the Dominican Republic

Phenotype logic (why it looks like this)

• Born with:
• male internal genitalia including testes (Wolffian structures ok because testosterone works)
• But have:
• female external genitalia
• often raised as girls
• (because external genitalia need DHT)

Puberty switch

• At puberty:
• ↑ LH secretion
• ↑ testosterone
• Develop:
• male body contours
• male libido
• Often change gender identity and “become boys”
• “Penis-at-12 syndrome”:
• clitoris enlarges enough for intercourse in some
• Proposed reason:
• high LH → so much testosterone that it partially compensates for missing DHT amplification in genital tissues

15) THERAPEUTIC HIGHLIGHT: 5α-REDUCTASE INHIBITORS

• Used for benign prostatic hyperplasia (BPH)
• Finasteride:
• greatest effect on type 2 5α-reductase

16) TESTICULAR PRODUCTION OF ESTROGENS (MALE ESTROGEN ECONOMY)

Where most male estrogen comes from

• >80% estradiol
• 95% estrone
• Produced by extragonadal + extra-adrenal aromatization
• from circulating testosterone + androstenedione

Testicular contribution

• Remaining fraction comes from testes:
• Some estradiol in testicular venous blood from Leydig cells
• Some produced by Sertoli cell aromatization of androgens

Male estradiol levels and production

• Plasma estradiol: 20–50 pg/mL (73–184 pmol/L)
• Total production rate: ~50 μg/day (184 nmol/day)

Age trend (opposite of testosterone trend)

• Estrogen production moderately increases with age in men

EXAM REFLEX BLOCKS (FAST LOCK)

Numbers to memorize

• Testosterone secretion: 4–9 mg/day
• Male testosterone: 300–1000 ng/dL
• Female testosterone: 30–70 ng/dL
• Bound fraction: 98%
• 65% SHBG/GBG
• 33% albumin
• Male estradiol: 20–50 pg/mL
• Estradiol production: ~50 μg/day
• DHT level: ~10% of testosterone

Pathway locks

• LH → Gs → ↑cAMP → PKA → cholesterol mobilization + pregnenolone formation
• Testosterone → Wolffian ducts (internal male)
• DHT → external male + prostate + facial hair + acne + male-pattern baldness
• Estrogen closes epiphyses (not androgen)

Traps

• Testosterone is NOT a 17-ketosteroid
• Etiocholanolone is a 17-ketosteroid but NOT androgenic
• Not all 17-ketosteroids are androgens; not all androgens are 17-ketosteroids

CONTROL OF TESTICULAR FUNCTION — COMPLETE LOGIC NOTE

1. CORE CONTROL AXIS (MASTER LOGIC)

Hypothalamic–Pituitary–Testicular (HPT) Axis

Hypothalamus → GnRH
                ↓
Anterior Pituitary → LH + FSH
      ↓                 ↓
 Leydig cells        Sertoli cells
      ↓                 ↓
 Testosterone     Spermatogenesis + Inhibin + ABP

2. ROLE OF PITUITARY GONADOTROPINS

FSH (Follicle-Stimulating Hormone)

• Tropic for: Sertoli cells
• Functions:
• Maintains gametogenic function (with androgens)
• Stimulates secretion of:
• ABP (androgen-binding protein)
• Inhibin
• Feedback:
• Inhibin inhibits FSH secretion
• Testosterone has little or no effect on FSH (except in very large doses)

LH (Luteinizing Hormone)

• Tropic for: Leydig cells
• Function:
• Stimulates testosterone secretion
• Feedback:
• Testosterone feeds back to inhibit:
• LH secretion (direct pituitary effect)
• GnRH secretion (hypothalamic effect)

Critical integrative point

• FSH + androgens together are required to maintain normal spermatogenesis
• Loss of hypothalamic input → testicular atrophy + loss of function

3. INHIBINS — WHY THEY EXIST

Key observation that led to discovery

• Testosterone ↓ LH, but does not suppress FSH
• Patients with:
• Seminiferous tubule atrophy
• Normal testosterone and LH
• → have elevated FSH

👉 Therefore: a testicular factor must specifically suppress FSH → INHIBIN

4. INHIBIN STRUCTURE & TYPES (EXAM-FAVORITE MOLECULAR LOGIC)

Subunits

• α subunit
• Glycosylated
• MW ≈ 18,000
• β subunits
• βA and βB
• Nonglycosylated
• MW ≈ 14,000 each
• All formed from precursor proteins

Inhibin molecules (heterodimers)

• α + βA → Inhibin A
• α + βB → Inhibin B
• Subunits linked by disulfide bonds

Physiologic role

• Both inhibit FSH secretion by direct pituitary action
• Inhibin B is the main FSH-regulating inhibin in:
• Adult men
• Adult women

Sites of production

• Males: Sertoli cells
• Females: Granulosa cells

5. ACTIVINS — THE OPPOSITE SIGNAL

Activin structures

• βAβB (heterodimer)
• βAβA (homodimer)
• βBβB (homodimer)

Action

• Stimulate FSH secretion
• → Oppose inhibin action

Physiologic role

• Exact reproductive role not fully settled

6. INHIBINS & ACTIVINS — FAMILY MEMBERSHIP

• Belong to TGF-β superfamily
• Includes MIS
• Activin receptors:
• Serine/threonine kinase receptors

7. EXTRA-GONADAL ROLES (IMPORTANT CONCEPT EXTENSION)

Distribution

• Inhibins and activins found in:
• Gonads
• Brain
• Many other tissues

Known roles

• Bone marrow: activins → white blood cell development
• Embryogenesis: activins → mesoderm formation

Genetic insight (high-yield)

• Targeted deletion of α-inhibin gene in mice:
• Normal early growth
• Later develop gonadal stromal tumors
• ⇒ α-inhibin gene = tumor suppressor gene

8. CIRCULATING BINDING & LOCAL MODULATION

In plasma

• α₂-macroglobulin binds:
• Inhibins
• Activins

In tissues

• Follistatins (4 glycoproteins) bind activins
• Binding:
• Inactivates activin biologic activity

Unresolved point

• Exact physiologic role of follistatins in inhibin regulation remains uncertain

9. STEROID FEEDBACK — WORKING MODEL

After castration

• ↑ Pituitary FSH and LH content & secretion

Hypothalamic lesions

• Prevent the post-castration rise of gonadotropins

Testosterone feedback

• Inhibits LH secretion by:
1. Direct action on anterior pituitary
2. Inhibition of GnRH secretion from hypothalamus

Inhibin feedback

• Acts directly on anterior pituitary
• Selectively inhibits FSH secretion

10. LOCAL ANDROGEN CONCENTRATION — WHY LH IS ESSENTIAL

In response to LH

• Leydig cells secrete testosterone
• Some testosterone:
• Bathes seminiferous epithelium
• Creates very high local androgen concentration
• This local androgen level is essential for spermatogenesis

Systemic testosterone paradox (EXAM CLASSIC)

• Systemic testosterone administration:
• ↓ LH secretion
• Does not raise intratesticular androgen sufficiently
• Net effect:
• ↓ sperm count

Contraceptive implications

• Testosterone proposed as male contraceptive
• Problems:
• Requires high doses
• Causes Na⁺ and water retention
• Inhibins being explored as alternative male contraceptives

ABNORMALITIES OF TESTICULAR FUNCTION

11. CRYPTORCHIDISM

Normal descent logic

1. Testes develop in abdominal cavity
2. Descent to inguinal region:
• Depends on MIS
3. Descent to scrotum:
• Depends on other factors

Cryptorchidism facts

• Incomplete descent in:
• ~10% of newborn males
• Locations:
• Abdominal cavity
• Inguinal canal
• Can be:
• Unilateral (more common)
• Bilateral (less common)

Natural course

• Spontaneous descent common:
• 2% at 1 year
• 0.3% after puberty

Why early treatment is recommended

• ↑ risk of malignant tumors
• High abdominal temperature damages:
• Spermatogenic epithelium
• Damage becomes irreversible after puberty

Management

• Gonadotropin therapy → may speed descent
• Surgical correction if needed

12. MALE HYPOGONADISM

Depends on timing of onset

• Before puberty
• After puberty

Adult hypogonadism — classification

Hypergonadotropic hypogonadism

• Primary testicular failure
• ↑ LH, ↑ FSH

Hypogonadotropic hypogonadism

• Secondary to:
• Pituitary disease
• Hypothalamic disease (e.g. Kallmann syndrome)
• ↓ LH, ↓ FSH

Loss of testicular endocrine function in adults

• Secondary sex characteristics regress slowly
• Very little androgen needed to maintain them
• Laryngeal growth is permanent
• Voice remains deep
• Libido ↓ but:
• Ability to copulate persists for some time
• Other features:
• Occasional hot flushes
• ↑ irritability
• More passive, depressed behavior

13. EUNUCHOIDISM (LEYDIG FAILURE FROM CHILDHOOD)

Body habitus

• Tall stature (epiphyses remain open)
• Not as tall as hyperpituitary giants
• Narrow shoulders
• Small muscles
• Female-like body configuration

Sexual characteristics

• Small genitalia
• High-pitched voice

Hair distribution

• Pubic & axillary hair present (adrenal androgens)
• Hair sparse
• Pubic hair pattern:
• Female triangle (base up)
• Instead of male escutcheon (base down)

14. ANDROGEN-SECRETING TUMORS

• Non-tumorous testicular “hyperfunction” does not exist
• Leydig cell tumors:
• Rare
• Endocrine symptoms seen mainly in prepubertal boys
• Cause precocious pseudopuberty

15. HORMONES & CANCER (PROSTATE)

• Some prostate carcinomas are androgen-dependent
• Tumors may regress temporarily with:
• Castration
• GnRH agonists (high dose)
• Cause GnRH receptor down-regulation
• ↓ LH secretion
• ↓ testosterone

EXAM REFLEX LOCK (ONE-LOOK SUMMARY)

Feedback control

• Testosterone → ↓ LH (pituitary + hypothalamus)
• Inhibin B → ↓ FSH (pituitary only)

Sertoli vs Leydig

• FSH → Sertoli → ABP + Inhibin + spermatogenesis
• LH → Leydig → testosterone

Key paradox

• Systemic testosterone → ↓ sperm count

Cryptorchidism

• Early treatment needed despite high spontaneous descent

Hypogonadism patterns

• Primary → ↑ LH/FSH
• Secondary → ↓ LH/FSH