1. Reproductive system physiology By Khorrami Ph.D. http://khorrami1962.spaces.live.com khorrami4@yahoo.com

2. Reproductive endocrinology Chromosome & genetic determinants, related abnormalities & syndromes. Enzymes that influence steroidogenesis. Brain, male type & female-type brain. sex and gender Puberty; theories & mechanisms involved Male reproductive organ, testis, spermatogenesis Female reproductive organ. Menstrual cycle; Ovulation, premenstrual syndrome ,follicle, hirsutism Fertilization; theories, decapacitation and capacitation. Placenta; hormonal action Physiologic changes during pregnancy Physiologic changes during pregnancy, endocrine disorders during pregnancy Parturition; pain, endocrinology of parturition Lactation; physiological functions of prolactin Menopause/ andropause Steroid hormones Growth factors Important hormones in reproductive system, prostaglandins, thromboxanes & leukotrienes & reproductive system Physiological actions of prostaglandins, pathological & their therapeutically usage Stem cell, cloning & related articles

4. Sexual reproduction Since 1 billion years ago Most important factor in development of life

5. Stages in sexual development Genetic Gonadal sex Phenotypic sex Neuronal sex Gender identity

6. Cytogenetic techniques Q-bands: identification of Y & 21, 22 Quinacrinehcl UV G-bands: identification of all chromosomes Giemsa Based on bands in homologous chromosomes C-bands: reflect constitutive heterochromatin Repetitive DNA without specified message Alkaline denaturation Interstitial location in Y Determine the origin of fault

11. Chromosomal faults Mosaism Chimerism

19. Autosomal gene Sox9 Ch;17 for sertoli cell differentiation

21. Sexual development

22. Sexual development

23. Genital development Wolfian duct Vasa deferent Seminal vesicle Epididymis Urogenital sinus Prostate Cowper’s gland Mullerian duct Fallopian tube Uterus Upper portion of vagina Urogenital sinus Lower vagina Bartholien glands

24. Sex differentiation

25. Sexual development

28. True hermaphrodism XX karyotype

30. Testicular feminization X-linked recessive End pouch vagina Testis No internal female organ Breast development Paucity of pubic hair

31. Abnormal development of reproductive system

34. Pathways of steroid hormone biosynthesis

36. estrone Estradiol

37. Adrenal/gonadal androgens

40. Steroidogenesis in adrenal androstenediol

42. 5-αreductase Finasteride (5-αreductase inhibitor)

43. Arenogenitalsyndrme 21β-hydroxylase deficiency Enlarged phalus Fused labioscrotal folds Hi MSH Tan skin

45. Metabolism of steroids:

48. Abbreviations: CYP11A1, cholesterolmside-chain cleavage enzyme; desmolase; CYP17, 17a-hydroxylase/17,20-lyase; 3b-HSD, 3b-hydroxysteroid dehydrogenase; CYP21A2, 21-hydroxylase; CYP11B1, 11b-hydroxylase; CYP11B2, aldosterone synthase, corticosterone 18-methylcorticosterone oxidase/lyase.

51. Mechanisms in brain differentiation Altering neuronal genomic expression Regional cell growth Proliferation Death, cell number, size, or packing density Early migrational patterns Dendritic growth Neuronal myelination

52. Brain types Sexually dimorphic nucleus of medial preoptic area (SDN-POA) male>2.5female Preoptic-anterior hypothalamic area Men: higher proportion of gray matter to cranial volume Women: higher proportion of white matter Women: larger corpus callosum No sex differences in general IQ Men typically excel in spacial & quantitative abilities Women: on tasks involving verbal abilities, perceptual speed and accuracy, and fine motor skills Men: more specialized skill

53. Alpha-feto-protein Is a globulin Produced by Fetal liver Yalk sac Starts at 4th week Max secretion at 24th week Absent at 24th week Regulate steroid hormones

54. Estrogen on brain Timing AFP SHBG

55. Brain differences

56. Brain types Male type brain Homosexuality Fraternal birth order effect Blanchard and Bogaert(1996): Maternal immune hypothesis

57. neurosteroids Sexual behavior Developmental enhancing effect Memory enhancing effect Pregnancy Stress

58. Progesterone & neurosteroids Schwann cells secrete progesterone, important in myelination Progesterone stimulate myelin protein synthesis Convert to 5α-OH prog. by 5α-reductase Then to 3α,5β-OH-prog. by 3α-OHS-oxidoreductase in glial cells, Act on GABA & NMDA receptor(potentiate)

60. Aromatase & breast cancer 1 Schematic of metabolic pathways in an ER-positive cell that can be affected by AIs. The left side represents the active pathways and cellular responses under normal estrogen control. The right side depicts the blockade of pathways involving ERs and the resultant cellular responses. AI, aromatase inhibitor; E2, estradiol; ER, estrogen receptor; MAP, mitogen-activated protein; PI-3, phosphoinositide-3; RTK, receptor tyrosine kinase; SERD, selective estrogen receptor down-regulator; SERM, selective estrogen receptor modulator

61. Androgen production 5α-reductase in: prostate Scrotum Penis Liver Hair follicles Skin Glial cells

62. These factors are essential for:

64. Gonadotropin secretion Testis activity: at 7th week Ovary activity: at 14th week Portal system is intact at 11.5th week Axon fibers of LRH in ME at 16th week Functional fetal LRH at the end of first trimester

66. puberty Factores affecting Mechanisms involved Gene or chromosome? Stages

67. Factors affecting puberty Genetic Geographic Socioeconomic Inheritance Altitude Life style(activity) Nutrition

69. Gonadotropin secretion pattern Tonic Cyclic

71. Control of HT on gonadotropin secretion Maturation of sex steroid receptors in LRH neurons Maturation of sex hormone-independent inhibitory pathways

72. Cyclic secretion of gonadotropins In men: LH: every 90-120min 1μg/min for 6min every hr Mid and late luteal phase: every 3-4 hrs

73. Gonadotropins Stimulator (on GnRH pulse) Inhibitor (on GnRH pulse) Adrenalin Noradrenalin Dopamine Estrogen PGs Histamine Bradykinin 5-HT Opioids Endorphin Enkephalin Progesterone Melatonin

74. HL: FSH>LH

76. Puberty gene GPR54 defect In Saudi family Hypogonadotrophichypogonadism Puberty delay Sexual infantilism Low GnRH but responsible pituitary to exogenous GnRH

77. Puberty gene GPR54 On chromosome 19 Encodes a Gprotein–coupled receptor A member of rhodopsin family of G-pr coupled receptor This receptoris essential for normal GnRH physiologyand for puberty. Metastin(kisspeptin-1) is an agonist on the same receptor Secreted by placenta Normal delivery Defect in X-linked kallmann’s syndrome

78. Gonadotropin regulation Sex hormone dependent In MBH & arcuate nucleus Sex hormone independent

79. Puberty stages Adrenarche (prepubertal) 2 year before second event SHBG increase in both sexes Gonadarche SHBG decrease more in boys

80. SHBG Stimulator: Estrogen Thyroid hormones In old ages Obesity Estrogen ↑ Androgen ↓ Inhibitor: GH (Acromegaly) Glucocorticoids(Cushing) Androgens Progestin

85. Negative feedback

90. Sleep-induced LH pulse

93. Control of adrenal cortex

94. Growth of adrenal

95. Adrenal cortex development

96. Dhea-s secretion

97. Hormones during puberty

98. Growth spurt during puberty Peripuberty Peak height velocity(PHV) Decrease velocity, epiphyseal fusion

100. Satiety hormones Ghrelin Obeststin Leptin Orexin Amylin

101. Oral androgens decrease high-density lipoprotein (HDL) cholesterol and increase low-density lipoprotein (LDL) cholesterol. selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene

102. Pineal gland Pinealocytes: produce and secret melatonin Peptidergic neuron-like cells Interstitial cells Perivascular phagocytes Pineal neurons Pineal calcification is hi in regions with hi frequency of breast cancer

103. melatonin Melatonin was discovered in 1958 By American physician Aaron B. Lerner Derivative of tryptophan

104. Melatonin secretion

106. Light signal transmition Retina SCN of HT PVN Intermediolateral cell column Superior cervical ganglia Pineal gland

108. Melatonin receptores Most abundant in SCN & anterior pituitary( pars tuberalis) Mel1A & Mel1B Block out the blue rays of light to avoid postpartum depression