22-01-24 Lecture 6. Male Endocrinology NW ( Updated) PDF

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Nick Werry | ANSC*3040 | [email protected]

Learning Goals • Understand endocrine control of reproduction in adult males of domestic species

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Abbreviations GnRH

Gonadotrophin Releasing Hormone

LH

Lutenizing Hormone

DHT

Dihydrotestosterone

FSH

Follicle Stimulating Hormone

Kp

Kisspeptin

Testosterone

INH

Inhibin

Anti-Müllerian Hormone

Ox

Oxytocin

T AMH

E2 Estradiol 3

Gubernaculum function

Tunic formation

Gubernaculum regression 5

Male development Mesonephric duct • Becomes epididymis + ductus deferens

Mesonephric tubules • Components of the mesonephros • Develop to become efferent ducts - Connect epididymis + rete testis

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Lecture 2: embryo + male

Lecture 3: female + neural

Lecture 4

• Developmental potency

• Trends in female-specific development

• Mechanisms to thermoregulate the testes

• Trends in broad ligament formation

• Recognition + functional biology of male anatomy

• Order of key developmental events

• Location + function of non-sperm cells in the testis parenchyma

• Origins + roles of the pituitary gland and hypothalamus

• Sperm movement, maturation, + storage in excurrent duct system

• Developmental stages of the early embryo • Trends in sexually independent development • Trends in male-specific development • Testis descent process + associated abnormalities

• Sexual differentiation of the hypothalamus

Lecture 5 • Differences between penis types • Functional biology of the penis • Species differences in male anatomy

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The Boys Timing • No issues with development • No difference in diameter of urethra

Penile spines • Induced by testosterone - Differentiate between castrated + cryptorchid Tom - Regress in absence of T http://www.thecatgroup.org.uk/policy_statements/neut.html

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Hormone interactions • Cooperation between Hypothalamus, Pituitary, Gonads • Various feedback loops - Hormone cycles are sex-dependent

Citation Figure modified from P.L. Senger 2015

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Sex Differences

Figure from P.L. Senger 2015

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Female Trends • Fetuses express ⍺-fetoprotein - Not expressed in adults

Surge centre

• Ovary releases estradiol - Binds ⍺FP

• Estradiol cannot pass Blood brain barrier

⍺FP

⍺FP

E2

E2

- No E2 in brain

• “Feminized” development - Surge centre develops

Fetal gonad 16

Male Trends

T

E2

• Fetuses express ⍺-fetoprotein

T

E2

- Not expressed in adults

No surge centre

• Testis releases testosterone - Does not bind ⍺FP

• Testosterone can pass blood brain barrier

⍺FP

⍺FP

- Converts to E2 in brain

• “Masculinized” development - Surge centre fails to develops

Fetal gonad 21

Comparison Female

Male

• Estradiol+⍺FP cannot penetrate BBB

• Testosterone does not bind ⍺FP, can penetrate BBB

• Surge centre develops

• Surge centre development inhibited

- Regulates hormonal surges

- Tonic centre regulates all expression Surge centre

No surge centre

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Hormone production Produces

Hypothalamus

• GnRH • CRH • TRH • PRH • GHRH • ADH • Oxytocin Figure modified from P.L. Senger 2015

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GnRH neurons Organization

Hypothalamus

• Surge centre (female only) • Tonic centre (F + M) • Paraventricular nucleus (F + M)

Structure • Axons extend into pituitary stalk • Axons terminate on capillary network

Anterior Lobe

Posterior Lobe

- Hypothalamic-hypophyseal portal Figure modified from P.L. Senger 2015

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Routes Standard system

Portal system

• Heart → artery → capillary network → vein → heart

• Heart → artery → capillary network → capillary network → vein → heart

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Standard blood flow PPP

• Heart → artery → capillary → vein → heart

SHA

- Posterior lobe

Portal systems • Heart → artery → capillary network → capillary network → vein → heart

SPP

- Anterior lobe

Citation Figure modified from P.L. Senger 2015

Vein

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Hypothalamic-hypophyseal portal PPP

• Blood from Superior Hypohyseal Artery

SHA

• GnRH axons deliver GnRH to PPP - Primary Portal Plexus: near posterior lobe

• Blood moves directly from PPP to SPP - Secondary Portal Plexus: near anterior lobe

LH GnRH

• Portal allows AP high sensitivity to GnRH

SPP

GnRH

LH

- Absorbed before circulating in body - Gonadotrophs in AP release LH + FSH

GnRH

FSH H

GnRH

Figure modified from P.L. Senger 2015 Citation

Vein

FSH

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Standard blood flow Ox

PVN axons enter posterior lobe • No portal system • Paraventricular nucleus produces Oxytocin - Axons enter posterior lobe - PL secretes Ox

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Comparison Anterior

Posterior

• Hypothalamic-hypophyseal portal • Standard blood supply • Signalled by GnRH neurons - Axons from Tonic or Surge centre

• Secretes FSH + LH

• Signalled by PVN of hypothalamus - Axons release hormones directly

• Secretes Ox

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HPG Axis Negative loop

Hypothalamus

• GnRH increases LH + FSH

GnRH

• LH increases T • T decreases GnRH - T pulse must subside before next GnRH pulse

T Testes

LH

FSH

Pituitary 37

In the male Trends • GnRH pulses: every 3-6h - Induces release of LH and FSH from anterior pitutary

• FSH pulses: short + wide - Limited by INH

• LH pulses: tall + thin - Last 30-60 mins Figure from P.L. Senger 2015

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In the male Trends • Leydig cells in testis have LH receptors • Testosterone produced in response to LH - T released in pulses - Low T allows new GnRH pulse

Figure from P.L. Senger 2015

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Cascade • Hypothalamus releases GnRH to PPP - Goes to anterior pituitary

• Anterior pituitary releases FSH + LH - Different pathways for each - Enters bloodstream, eventually reach testes

• Leydig cells produce T

GnRH

- Enters bloodstream, eventually reaches brain - Inhibits GnRH Testis LH FSH Citation Figure modified from P.L. Senger 2015

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Feedback loop Negative loop • GnRH increases LH + FSH

GnRH

• LH increases T • T decreases GnRH - T pulse must subside before next GnRH pulse

• FSH increases INH • Inhibin decreases FSH

T

LH

FSH

INH

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Testis cells Leydig (interstitial endocrine)

Hypothalamus

• Bind LH → produce T

GnRH

Sertoli (testicular sustentacular) • Bind FSH → produce INH • Bind T → produce DHT + E2 T Leydig

LH

FSH

Anterior pituitary

INH

Sertoli 48

Supplemental T use Benefits

Consequences

• T promotes muscle growth • T needed for male libido

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Regulate GnRH Family of peptides • Stimulate GnRH production • Respond to steroid hormones (T, E2) - Inhibited

T

Kp

GnRH 50

Feedback loop Kisspeptin

Hypothalamus

• Facilitates T suppression of GnRH

GnRH

Kp

T Leydig

LH

FSH

Anterior pituitary

INH

Sertoli 52

Summary

Negative feedback via Kisspeptin

• GnRH goes to anterior pituitary, causes release of LH + FSH • LH causes Leydig cells to make T - Supports Sertoli cell function

• Testosterone - Inhibits production of GnRH via Kp - Some converted to DHT, E2

• Inhibin - From Sertoli cell inhibits FSH - FSH stimulates INH Citation Figure modified from P.L. Senger 2015

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Negative feedback via Kisspeptin

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Consistent pattern across days

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Key ideas • Differences in bloodflow between pituitary lobes • Relationships between male hormones - Cyclicality - Feedback loops

• Locations of activity of male hormones

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