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Reproduction Section

Reproduction Section. Human Physiology ( University Honors College) Fall Semester, 2013. Hypothalamo-pituitary axis. GnRH Neurons. Relationship of GnRH to LH Secretion. GnRH pulse Frequency on Pituitary. GnRH regulation of LH and FSH. Regulation, GnRH.

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Reproduction Section

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  1. Reproduction Section Human Physiology (University Honors College) Fall Semester, 2013

  2. Hypothalamo-pituitary axis

  3. GnRH Neurons

  4. Relationship of GnRH to LH Secretion

  5. GnRH pulse Frequency on Pituitary

  6. GnRH regulation of LH and FSH

  7. Regulation, GnRH

  8. Regulatory neurotransmitters in Medial Basal Hypothalamus

  9. Testis Gross Anatomy • Human testis is divided into 250-400 lobules • Each lobule contains 2-4 seminiferous tubules • Each seminiferous tubule is about 2 meter in length • Sperm are produced in seminiferous tubules and transported via the rete testis and efferent ductules to the epididymis • Further maturation of sperm occurs in the epididymis

  10. Sperm Transport and Maturation • Transport – epididymis, vas deferens, urethra • Epdidymis – sperm are concentrated, mature and become motile • Ampulla - storage • Accessory glands – Prostate, seminal vesicles and cowpers produce seminal fluid

  11. Testis

  12. Testes: Seminiferous tubules & Interstitial cells of Leydig

  13. Spermatogenesis

  14. Seminif. Tubule Microenvironment

  15. Sperm Function • Carry and protect the haploid genome • Transport through the male and female reproductive tracts • Fertilize the oocyte Sperm Structure • Sperm Head • Acrosome – specialized lysosome containing hyaluronidase and acrosin • Nucleus – contains the haploid male genome • Midpiece • Mitochondrial sheath • Tail • Axoneme with a 9+2 arrangement of microtubules for movement.

  16. Regulation of the Hypothalamic-Pituitary-Testis Axis Negative Feedback (GnRH) Negative Feedback (LH) Negative Feedback (FSH)

  17. Serum LH concentrations in normal and hypogonadal men Normal ng/ml Hypogonadal ng/ml

  18. Mechanisms of Testosterone Action • Diffuse into cell, combine with AR, enter nucleus, activate gene expression (predominates in muscle and testis) • Diffuse into cell, convert to DHT by 5a-reductase (external genitalia and skin) • Diffuse into cell, convert to Estradiol by P450 aromatase (Bone and ~negative feedback on LH) This is non-AR mediated. • ‘Non classical’: Testosterone binds to AR, but then associates with kinases that cause increases in kinase-mediated pathways – this happens within 1 minute of binding – too fast for transcription. (Likely actions are directly on Sertoli Cell and on Germ cell.)

  19. Erectile function/dysfunction Erectile dysfunction drugs (Viagra, Cialis, Levitra) inhibit the PDE5 phosphodiesterase and prevent degradation of the cGMP signal.

  20. Hemodynamic Events Associated With Erection GTP cGMP GMP Nitric oxide PDE5 Viagra

  21. Regulation: ovarian cycle Estradiol feedback: - primarily pituitary, + both pituitary and hypothalamus. Progesterone: - hypothalamus

  22. LH patterns during menstrual cycle

  23. Hormonal changes during the menstrual cycle

  24. Evaluation of patient for intact reproductive axis • Presentation with symptoms suggesting hypogonadal status: • Female • Infrequent or absent menstrual cycles • Hot flashes Male Impotence Infertility

  25. Evaluation of Patient for intact reproductive axis • Determine circulating steroid levels • High or normal (unlikely with presentation for impotence or hot flashes). If found, may indicate gonadal tumor. • Low levels, evaluate gonadotropins • Determine circulating gonadotropin levels • High levels, gonadal problem • Low levels, pituitary or hypothalamic problem

  26. Evaluation of Patient for intact reproductive axis • Determination of low levels of gonadotropin • Evaluate response to GnRH injection • Increased LH, likely to be hypothalamic problem • No increase LH or FSH, pituitary problem • Quality of gonadotropin response to GnRH injection can suggest history/timecourse of problem

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