1. PUBERTY Gonadal maturation with acquisition of secondary sexual characteristics and associated growth spurt FERTILITY AND FINAL HEIGHT

2. Genetic Sex Phenotypic Sex XX XY Testis-determining genes Ovary-determining genes Gonadal steroids & peptides (T, DHT, MIS) Gonadal steroids (E 2, P 4 ) Sex Determination Gonadal Sex

4. Bipotential Gonad Genetic Pathway for Testis Development Testis DevelopmentTestis Function Leydig -Testosterone Sertoli -AMH -ABP -Inhibin B Germ cells -Spermatogenesis Sf1 Sry Wnt4 ↓ ↓ Dax1 Sox9 Sox8 Insulin/IGF Gata4/Fog2 Wt1 Sf1 Wt1 Sf1 Dmrt1 M33 Emx2 Lim1 Lhx9 Fgf9 Fgfr2 Sf1 Atrx Dhh Pdgf Dax1 Vascularization Germ cell migration/proliferation Inhibition of PGC meiosis Sertoli proliferation/differentiation Leydig cell migration/differentiation PTM cell migration/proliferation Testis cord formation

5. Morphologic Steps in Testis Development XY XX Brennan J, Capel B: Nat Rev Genet 5: 509, 2004 Proliferation Sertoli Differentiation Migration Testis cords Vascularization Leydig cells

6. Gonads Pituitary LH FSH GnRH LH pulses GnRH pulses E2 P Inhibin Hypothalamus T

7. Close Window Figure 2 Proposed mechanism for the induction of puberty in humans. Before puberty, the hypothalamus is sensitive to very small concentrations of sex steroids and stops LRF production, thereby halting further steroid synthesis. Sex steroids are kept at low levels. At the onset of puberty, the hypothalamus becomes progressively less sensitive to the sex steroids, thereby allowing more of them to be synthesized, until finally the adult level of sex steroids is achieved. Relative widths of arrows indicate levels of hormone production. (After Grumbach et al., 1974.) Close Window

10. PUBERTY Gonadal maturation with acquisition of secondary sexual characteristics and associated growth spurt FERTILITY AND FINAL HEIGHT

11. PUBERTY Average age of onset: 11.4 years in girls 12.0 years in boys First signs of pubertal maturation: breast budding in girls increase in testicular volume in boys

12. TANNER’S STAGING OF PUBERTY IN BOYS

14. Testosterone produced by Leyding cells induces/ maintains secondary sexual characteristics and sustain germ cell production Virilization of external genitalia Phallus growth Pubic, axillary, facial hair Libido Erections/ejaculate Voice change Body composition Bone mineralization

16. CONCERNS RAISED BY DELAYED PUBERTY Possibly sinister underlying cause Fear that puberty will never occur Emotional and psychosocial upset of immaturity, specially when associated with short stature Long term sequelae: ? Reduced bone mineralization

17. DELAYED PUBERTY Absence of a clear pattern of pulsatile gonadotrophin secretion Pre-pubertal LH and FSH levels Development of secondary sexual characteristics Normal "Consonance" Bone age delay Final height is not impaired except if severe degree of delay

18. Male Homosexuality: Nature or Culture? 1500 species Data mostly in males: more common more studied more confronted by religion Genetic Autoimmune Neurohormonal Jannini 2010

19. Nature - BIOLOGY Cause or result Inherited from the mother

20. Brain Anatomy Swaab 2004

21. Nature – Culture Biology Older brother – more biological brothers ++ more immunity? Fertility Advantage of carrying the HM gene (Camperio-Ciani 2008) Ratio of 2D:4D (lower-male, higher-female) Nature does not deny Nurture Culture denies Nature!

22. Older brothers and hand preference

23. “Half Woman”??? Testosterone-higher (Brodie 1974, Jannini 2009) Testicular feminization example CAH Fetal Brain epigenetics Sexual activity - higher

24. Penis-Longer (Ghanem 2007) (Bogaret 1999)

25. Nature recent genetic study 2005 a full genome scan 456 individuals from 146 families with two or more homosexual brothers 3 locuses and X chromosome 28q

26. A genome-wide scan of male sexual orientation Journal of Human Genetics (2010) 55 Sreeram V Ramagopalan, Journal of Human Genetics (2010)

27. Culture low paternal presence, high maternal cures Oedipus Diagnostic and Statistical Manual of Psychological Disorders (DSM-IV-TR) - “homosexuality” absent

28. Culture early childhood traumas propose a reparative therapy based on psychoanalysis, group therapy, and spiritual help