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  1. 1. ENDOKRINOLOGI REPRODUKSI Bayu Kurniawan, dr .
  2. 2. Topik Pembelajaran <ul><li>Dasar Endokrinologi Reproduksi Wanita </li></ul><ul><li>Dasar Endokrinologi Reproduksi Pria </li></ul>
  3. 3. Dasar Endokrinologi Reproduksi Wanita
  4. 4. Tujuan Pembelajaran <ul><li>Mahasiswa mampu memahami & menjelaskan : </li></ul><ul><ul><li> Fenotip wanita </li></ul></ul><ul><ul><li> Sistem endokrin & reproduksi </li></ul></ul><ul><ul><li> Konsep Menstruasi </li></ul></ul>
  5. 5. THE FEMALE - PHENOTYPE <ul><li>What makes a woman ? </li></ul><ul><li>1. Chromosomal composition of female is XX </li></ul><ul><li>2. Gonads that are functionally and structurally ovaries </li></ul><ul><li>3. Female sex hormone production </li></ul><ul><li>4. Appropriate internal and external genitalia </li></ul><ul><li>5. Self - Acceptance of female role </li></ul>
  6. 6. Endocrine System <ul><li>Communication system </li></ul><ul><ul><li>Allows for cells in distant parts of body to communicate </li></ul></ul><ul><ul><li>Communication generally slower in onset, but longer in duration, compared to nervous system communication </li></ul></ul><ul><li>Consists of all the organs that secrete hormones (endocrine organs) </li></ul>
  7. 7. Hormones <ul><li>Chemical Messengers </li></ul><ul><li>Produced by an endocrine gland </li></ul><ul><li>Released into and carried via bloodstream to target tissues </li></ul><ul><ul><li>Target tissues = tissues bearing receptors that can bind and physiologically respond to the chemical messenger in question </li></ul></ul><ul><ul><li>Amount of chemical messenger produced and released intocirculation is generally very small </li></ul></ul>
  8. 8. SEX HORMONES - FEMALE 1. Gonadotrophin-releasing hormone (GnRH) (decapeptide) LH Releasing Factor, FSH Releasing Factor 2. Luteinising hormones (LH) 3. Follicle stimulating hormone (FSH) 4. Inhibin (Protein hormone) 5. Activin (Protein hormone) 6. estrogens, progesterons & androgens Peptides Steroids Hormones responsible for development and maintenance of female phenotype:
  9. 9. TRADITIONAL ENDOCRINE SYSTEM general blood circulation capillary Feedback loop A B stimulus nucleus hormone Hormone producing cell second messengers Ca 2+ Norman, A.W.; Litwack, G. (1997) Hormones 2nd Ed. Academic Press Target Cell hormone
  10. 10. Reproductive System <ul><li>Survival of the organism </li></ul><ul><ul><li>Other systems of the body work together to maintain homeostasis and promote survival of the organism under varying environmental conditions </li></ul></ul><ul><li>Survival of the species </li></ul><ul><ul><li>Reproductive system is designed to package and transmit genetic information from generation to generation, therefore promotes survival of the species over time </li></ul></ul>
  11. 11. Major Functions of Male and Female Reproductive Systems <ul><li>Production of gametes </li></ul><ul><ul><li>Male gametes = sperm </li></ul></ul><ul><ul><ul><li>Spermatogenesis = production of mature sperm </li></ul></ul></ul><ul><ul><li>Female gametes = eggs (ova) </li></ul></ul><ul><ul><ul><li>Oogenesis = production of mature eggs </li></ul></ul></ul><ul><li>Steroidogenesis </li></ul><ul><ul><li>Production of steroid hormones </li></ul></ul><ul><ul><ul><li>estrogens, progesterons, androgens </li></ul></ul></ul>
  12. 12. PEPTIDE/ PROTEIN HORMONES INVOLVED IN FEMALE DEVELOPMENT AND REPRODUCTION <ul><li>Hormone Site of Principal target tissue Biological function </li></ul><ul><li> Production </li></ul><ul><li>GnRH Hypothalmus Adenohypophysis Stimulation of release of </li></ul><ul><li> FSH and LH </li></ul><ul><li>FSH Adenohypo- Ovarian Granulosa Growth ovarian follicle </li></ul><ul><li> physis and thecal cells Stimulation estrogen </li></ul><ul><li> production </li></ul><ul><li> </li></ul><ul><li>LH Adenohypo- Corpus luteum Stimulate progesterone </li></ul><ul><li> physis production </li></ul><ul><li>Inhibin Follicle granulosa Hypothalmus- Participate in feedback </li></ul><ul><li> cell pituitary inhibition of FSH secretion </li></ul><ul><li>Activin Follicle granulosa Hypothalmus Increase secretion of FSH </li></ul><ul><li> </li></ul>
  13. 13. Female Reproductive System (1) <ul><li>Fase Intrauterine </li></ul><ul><li>Fase Bayi </li></ul><ul><li>Fase Anak </li></ul><ul><li>Fase Pra-pubertas </li></ul><ul><li>Fase Reproduksi </li></ul><ul><li>Fase Klimakterium </li></ul><ul><li>Fase Senium </li></ul>
  14. 14. Female Reproductive System (2) <ul><li>Poros Hormon Reproduksi </li></ul><ul><li>- Susunan Sentral </li></ul><ul><li>- Pineal </li></ul><ul><li>- Hipotalamus </li></ul><ul><li>- Hipofise </li></ul><ul><li>- Susunan Perifer </li></ul><ul><li>- Ovarium </li></ul><ul><li>- Endometrium </li></ul><ul><li>Organ Endokrin Ekstra Gonad </li></ul><ul><li>- Timus </li></ul><ul><li>- Tiroid </li></ul><ul><li>- Adrenal </li></ul><ul><li>- Pankreas </li></ul>
  15. 15. PINEAL (1) <ul><li>Kelenjar kecil di posterior hipotalamus </li></ul><ul><li>Embriologis berasal dari diensefalon posterior </li></ul><ul><li>Organ sisa ? </li></ul>
  16. 16. PINEAL (2) <ul><li>Sintesis </li></ul><ul><ul><li>Melatonin (>> aktif) </li></ul></ul><ul><ul><li>5-Metoksi-Triptofol </li></ul></ul><ul><ul><li>Arginin Vasotosin </li></ul></ul><ul><li>Sekresi </li></ul><ul><ul><li>Belum seluruhnya diketahui </li></ul></ul><ul><ul><li>Irama Sirkadian, Pulsatil (Melatonin) </li></ul></ul>
  17. 17. PINEAL (3) <ul><li>Fungsi </li></ul><ul><ul><li>Belum seluruhnya diketahui </li></ul></ul><ul><ul><li>Dipengaruhi cahaya & hormon </li></ul></ul><ul><ul><li>Terdapat reseptor hormon steroid seks & prolaktin </li></ul></ul><ul><ul><li>Berpengaruh terhadap : </li></ul></ul><ul><li>- Poros hipotalamus-hipofise-gonad </li></ul><ul><li>- Reproduksi </li></ul><ul><li>- Siklus Seksual & Siklus haid </li></ul><ul><li>- Seks Sekunder </li></ul><ul><li>- Genitalia Interna </li></ul><ul><li>- Ovulasi </li></ul>
  18. 18. Hypothalamic-Pituitary Axis <ul><li>Hypothalamus </li></ul><ul><ul><li>Region of brain (diencephalon) </li></ul></ul><ul><ul><li>Lies below third ventricle at base of brain </li></ul></ul><ul><ul><li>Important regulator of endocrine action </li></ul></ul><ul><li>Pituitary Gland (hypophysis) </li></ul><ul><ul><li>Endocrine gland connected to hypothalamus by infundibulum (stalk containing nerves and small blood vessels) </li></ul></ul>
  19. 19. Hypothalamus (1) <ul><li>Contains neuroendocrine cells that release neurohormones which </li></ul><ul><ul><li>1. enter the portal vessels and are transported to anterior pituitary </li></ul></ul><ul><ul><li>2. regulate anterior pituitary hormone production </li></ul></ul><ul><li>Contains neuroendocrine cells whose </li></ul><ul><ul><li>cell bodies lie within hypothalamus </li></ul></ul><ul><ul><ul><li>Hypothalamus = site of hormone production </li></ul></ul></ul><ul><ul><li>axons travel through hypothalamic-pituitary stalk and terminate in posterior pituitary </li></ul></ul><ul><ul><ul><li>Posterior pituitary = site of hormone storage and release </li></ul></ul></ul>
  20. 20. Hypothalamus (2) <ul><li>Hypothalamus Hormones </li></ul><ul><li>Hypothalamic Releasing Hormones </li></ul><ul><li>Hypothalamic Inhibitory Hormones </li></ul>
  21. 21. Hypothalamic Releasing Hormones <ul><li>Produced in and released from hypothalamus </li></ul><ul><li>Enter portal blood vessels and are transported to ANTERIOR PITUITARY </li></ul><ul><li>Stimulate discrete cell types within anterior pituitary to secrete additional hormone(s) </li></ul>
  22. 22. Hypothalamic Releasing Hormones <ul><li>Corticotropin Releasing Hormone (CRH) </li></ul><ul><ul><li>Acts on corticotrophs </li></ul></ul><ul><ul><li>Stimulates AP production of adrenocorticotropic hormone (ACTH) </li></ul></ul><ul><li>Thyrotropin Releasing Hormone (TRH) </li></ul><ul><ul><li>Acts on thyrotrophs </li></ul></ul><ul><ul><li>Stimulates AP production of Thyroid Stimulating Hormone (TSH) </li></ul></ul>
  23. 23. Hypothalamic Releasing Hormones <ul><li>Gonadotropin Releasing Hormone (GnRH) </li></ul><ul><ul><li>Previously known as Luteinizing Hormone Releasing Hormone (LHRH) </li></ul></ul><ul><ul><li>Acts on lactotrophs to stimulate AP production of Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) </li></ul></ul>
  24. 24. Hypothalamic Releasing & Inhibitory Hormones <ul><li>Growth Hormone Releasing Hormone (GHRH = somatotropin) </li></ul><ul><ul><li>Acts on somatotrophs </li></ul></ul><ul><ul><li>Stimulates AP production of Growth Hormone (GH) </li></ul></ul><ul><li>Growth Hormone Inhibitory Hormone (GIH = somatostatin) </li></ul><ul><ul><li>Acts on somatotrophs </li></ul></ul><ul><ul><li>Inhibits AP production of Growth Hormone </li></ul></ul>
  25. 25. Pituitary Gland <ul><li>In humans has two lobes = distinct glands </li></ul><ul><ul><li>Anterior (toward front of head) lobe = adenohypophysis </li></ul></ul><ul><ul><li>Posterior (toward back of head) lobe = neurohypophysis </li></ul></ul><ul><li>Lobes connected to hypothalamus by different means </li></ul><ul><ul><li>Anterior lobe connected by (portal) blood vessels </li></ul></ul><ul><ul><li>Posterior lobe connected by nerves (axons) </li></ul></ul>
  26. 26. Anterior Pituitary (AP) <ul><li>Endocrine (hormone-secreting) gland containing several different cells types </li></ul><ul><ul><li>Lactotrophs; secrete prolactin </li></ul></ul><ul><ul><li>Gonadotrophs; secrete LH and FSH </li></ul></ul><ul><ul><li>Somatotrophs; secrete Growth hormone </li></ul></ul><ul><ul><li>Thyrotrophs; secrete Thyroid stimulating hormone </li></ul></ul><ul><ul><li>Corticotrophs; secrete Adrenocorticotropic Hormone </li></ul></ul><ul><li>Connected to hypothalamus by portal blood vessels </li></ul>
  27. 27. Prolaktin <ul><li>Fungsi </li></ul><ul><ul><ul><li>Merangsang galaktopoeisis (mempertahankan laktasi & laktogenesis untuk membentuk air susu) </li></ul></ul></ul><ul><ul><ul><li>Memicu mammogenesis </li></ul></ul></ul>
  28. 28. FSH & LH <ul><li>Fungsi </li></ul><ul><li>- Pematangan folikel </li></ul><ul><li>- Ovulasi </li></ul><ul><li>- Pembentukan korpus luteum </li></ul><ul><li>- Sintesis steroid seks </li></ul>
  29. 29. Posterior Pituitary <ul><li>Outgrowth of the hypothalamus; composed of neural tissue </li></ul><ul><li>Specific neuroendocrine cells in hypothalamus have axons that project through the stalk and into the posterior pituitary </li></ul><ul><li>Secretes two important hormones </li></ul><ul><ul><li>Oxytocin (OXY) </li></ul></ul><ul><ul><li>Antidiuretic hormone (ADH) </li></ul></ul>
  30. 30. <ul><li>Fungsi Oxytocin </li></ul><ul><li>Persalinan : kontraksi uterus </li></ul><ul><li>Pengeluaran air susu dgn kontraksi mioepitel payudara </li></ul><ul><li>Fungsi ADH </li></ul><ul><li>Mengendalikan osmolalitas & volume plasma </li></ul>
  31. 31. Ovarium <ul><li>Fungsi Utama </li></ul><ul><li>1. Fungsi Proliferatif </li></ul><ul><li>Sumber ovum selama fase reproduksi </li></ul><ul><li>2. Fungsi Sekretorik </li></ul><ul><li>Pembentukan & pengeluaran hormon steroid seks (estrogen, progesteron & androgen) </li></ul>
  32. 32. Estrogen (1) <ul><li>Hormon steroid dgn 10 atom C, dibentuk dari 17-ketosteroid androstendion </li></ul><ul><li>Estrogen alamiah : estradiol (E2), estron (E1), estriol (E3) E2:E1:E3 = 10:5:1 </li></ul><ul><li>Disintesis di ovarium, adrenal, plasenta, testis, jaringan lemak, SSP </li></ul>
  33. 33. Estrogen (2) <ul><li>Khasiat Umum </li></ul><ul><li>- Merangsang sintesis DNA melalui RNA </li></ul><ul><li>- Membentuk messenger RNA </li></ul><ul><li>Meningkatkan sintesa protein </li></ul>
  34. 34. Estrogen (3) <ul><li>Khasiat Khusus </li></ul><ul><li>- Endometrium : memicu proliferasi endometrium, memperkuat kontraksi uterus </li></ul><ul><li>- Serviks : mengubah konsentrasi getah serviks saat ovulasi </li></ul><ul><li>- Vagina : perubahan selaput vagina, meningkatkan produksi getah, meningkatkan kadar glikogen, peningkatan produksi asam laktat, memperkecil kemungkinan infeksi </li></ul><ul><li>- Ovarium : memicu sintesis reseptor FSH & LH, mengatur kecepatan keluarnya ovum, mempersiapkan spermatozoa </li></ul>
  35. 35. Estrogen (4) <ul><li>Others: </li></ul><ul><li>Increase clotting factors in the blood </li></ul><ul><li>Decrease rate of bone resorption </li></ul><ul><li>Increase sodium and water retention </li></ul><ul><li>Mood & behavior </li></ul><ul><li>Spermatogenesis </li></ul><ul><li>Increase HDL and decrease LDL </li></ul>
  36. 36. Progesteron (1) <ul><li>Hormon steroid dgn 21 atom C </li></ul><ul><li>Dibentuk di folikel, plasenta & adrenal </li></ul><ul><li>Khasiat Umum </li></ul><ul><li>Mempersiapkan tubuh untuk kehamilan </li></ul><ul><li>(syarat mutlak konsepsi & implantasi) </li></ul><ul><li>Terjadi karena pengaruh estradiol, karena estradiol mensintesis reseptor progesteron </li></ul>
  37. 37. Progesteron (2) <ul><li>Khasiat Khusus </li></ul><ul><li>- Endometrium : perubahan sekretorik </li></ul><ul><li> (fase luteal) </li></ul><ul><li>- Serviks : barier terhadap spermatozoa </li></ul><ul><li> (fase luteal) </li></ul><ul><li>- Miometrium : menurunkan tonus miometrium </li></ul><ul><li>- Suhu Basal Badan : peningkatan suhu basal badan segera setelah ovulasi (termogenik) </li></ul>
  38. 38. Androgens: Physiological & Pharmacological Actions <ul><li>Necessary for development of male fetus </li></ul><ul><li>Responsible for major changes that occur in males at puberty </li></ul><ul><li>Anabolic actions </li></ul><ul><li>Maintains sexual function in males </li></ul><ul><li>Participates in pubertal growth spurt & hair growth in females </li></ul>
  39. 39. Endometrium <ul><li>Fungsi </li></ul><ul><ul><li>Nidasi </li></ul></ul><ul><ul><li> Menstruasi </li></ul></ul><ul><ul><li> Petunjuk gangguan fungsional & steroid seks </li></ul></ul>
  40. 40. Organ Endokrin Ekstra Gonad <ul><li>Thymus </li></ul><ul><li>Thyroid </li></ul><ul><li>Adrenal </li></ul><ul><li>Pankreas </li></ul>
  41. 41. THYMUS <ul><ul><li>Berubah mengikuti usia </li></ul></ul><ul><ul><li>Tumbuh kembang </li></ul></ul><ul><ul><li>Puncak sesaat sebelum pubertas </li></ul></ul><ul><ul><li>Aktivasi Hypothalamic- Pituitary Axis </li></ul></ul><ul><ul><li>Terdapat reseptor estrogen & androgen </li></ul></ul>
  42. 42. THYMUS <ul><li>Sekresi & Fungsi </li></ul><ul><li>- Timosin a-1 & Timosin β -4 </li></ul><ul><ul><ul><li>Aktivasi sekresi LH-RH Hipotalamus </li></ul></ul></ul><ul><ul><ul><li>Sekresi kortikosteroid </li></ul></ul></ul><ul><li>- Didapatkan Oksitosin & Vasopresin </li></ul><ul><ul><ul><li>Fungsi ??? </li></ul></ul></ul><ul><ul><ul><li>Parakrin </li></ul></ul></ul>
  43. 43. THYROID <ul><li>Sekresi Hormon Thyroxin </li></ul><ul><li>Gangguan sekresi : Hipertiroid – Hipotiroid </li></ul><ul><li>Hipertiroid </li></ul><ul><li>- Gangguan silkus haid (ringan) </li></ul><ul><li>Hipotiroid </li></ul><ul><li>- Gangguan fertilitas </li></ul><ul><li> (gangguan siklus haid berat sd anovulasi) </li></ul><ul><li>- Galaktorea </li></ul>
  44. 44. Hipotiroid <ul><li>T3 & T4 rendah </li></ul><ul><li>TRH tinggi </li></ul><ul><li>PRL tinggi </li></ul><ul><li>PRL hambat FSH & LH </li></ul><ul><li>Tingkatkan kadar androgen </li></ul><ul><li>Hambat pematangan folikel </li></ul>
  45. 45. Adrenal <ul><li>Produksi androgen wanita : ovarium & adrenal </li></ul><ul><li>>>> berlebihan >>> Ggn. Reproduksi </li></ul><ul><li>Intake kalori +++ >>> aktivitas adrenal </li></ul><ul><li>meningkat </li></ul><ul><li>Androgen +++ >>> Ggn. Gonadostat </li></ul><ul><li>hipotalamus-hipofise >> Ggn. Hypothalamic- </li></ul><ul><li>Pituitary Axis >>Resistensi folikel ovarium </li></ul>
  46. 46. Pankreas <ul><li>Sekresi Insulin </li></ul><ul><li>Normal: Insulin merangsang FSH – LH (Hipofise) </li></ul><ul><li>Fungsi : </li></ul><ul><li>- meningkatnya sintesis estrogen & progesteron </li></ul><ul><li>- sintesis & sekresi proteoglikan & </li></ul><ul><li> aktivator plasminogen </li></ul><ul><li>- timbulnya reseptor LH & Prolaktin </li></ul><ul><li>Kadar Insulin ~ Kadar androgen (androstendion & testosteron) </li></ul><ul><li>Obesitas – Anovulasi - Hirsutisme </li></ul>
  47. 47. PROSTAGLANDIN <ul><li>Ovulasi </li></ul><ul><li>Memicu pecahnya folikel dg mempengaruhi vaskuler & kontraksi ovarium </li></ul><ul><li>Spermatozoa </li></ul><ul><li>PG dari spermatozoa >> kontraksi & relaksasi uterus – tuba </li></ul><ul><li>Menstruasi </li></ul><ul><li>Merangsang otot polos </li></ul><ul><li>Dismenorea </li></ul><ul><li>Hiperkontraktilitas uterus (kadar progesteron rendah) </li></ul>Hubungan PG dg Sistem Reproduksi Wanita
  48. 48. TERIMA KASIH