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PUBERTY Gonadal maturation with acquisition of secondary sexual characteristics and associated growth spurt FERTILITY AND FINAL HEIGHT Sex Determination Genetic Sex XY XX Ovary-determining genes Testis-determining genes Gonadal Sex Gonadal steroids (E2, P4) Gonadal steroids & peptides (T, DHT, MIS) Phenotypic Sex Genetic Pathway for Testis Development Bipotential Gonad Wt1 Sf1 Dmrt1 M33 Emx2 Lim1 Lhx9 Insulin/IGF Gata4/Fog2 Wt1 Sf1 Testis Development Sry Sox9 Sox8 Dax1 Wnt4 ↓ Sf1 Atrx Dhh Pdgf Fgf9 Fgfr2 Sf1 ↓ Dax1 Testis Function Leydig -Testosterone Sertoli -AMH -ABP -Inhibin B Germ cells •Vascularization -Spermatogenesis •Germ cell migration/proliferation •Inhibition of PGC meiosis •Sertoli proliferation/differentiation •Leydig cell migration/differentiation •PTM cell migration/proliferation •Testis cord formation Morphologic Steps in Testis Development Proliferation Sertoli Differentiation Migration Testis cords Vascularization Leydig cells Brennan J, Capel B: Nat Rev Genet 5: 509, 2004 XY XX Hypothalamus GnRH pulses GnRH LH pulses Pituitary LH FSH Gonads T P E2 Inhibin Close Window e induction of puberty in humans. Before puberty, the hypothalamus is sensitive to very small concentrations of sex steroids and stops LRF Figure 2 roid synthesis. Sex steroids are kept at low levels. At the onset of puberty, the hypothalamus becomes progressively less sensitive to the sex steroids, 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 PUBERTY Gonadal maturation with acquisition of secondary sexual characteristics and associated growth spurt FERTILITY AND FINAL HEIGHT 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 TANNER’S STAGING OF PUBERTY IN BOYS STAGE GENITAL MATURITY (G) PUBIC HAIR (PH) 1 Prepubertal; testes 2 ml None 2 Enlargement of the A few darker hairs at the basis testes 4 ml; reddening of the penis of the scrotum 3 Lengthening of the Curly pigmented hairs across penis; further pubes enlargement of testes to 6-10 ml 4 Broadening of the Small adult configuration glands penis; growth of testis to 10-15 ml 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 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 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 Male Homosexuality: Nature or Culture? • 1500 species • Data mostly in males: more common more studied more confronted by religion • Genetic • Autoimmune • Neurohormonal Jannini 2010 Nature - BIOLOGY Inherited from the mother Cause or result Brain Anatomy Swaab 2004 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! Older brothers and hand preference “Half Woman”??? Testosterone higher (Brodie 1974, Jannini 2009) Testicular feminization example CAH Fetal Brain epigenetics Sexual activity - higher Penis - Longer (Ghanem 2007) (Bogaret 1999) 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 A genome-wide scan of male sexual orientation Journal of Human Genetics (2010) 55 Sreeram V Ramagopalan, Journal of Human Genetics (2010) Culture • low paternal presence, high maternal cures • Oedipus Diagnostic and Statistical Manual of Psychological Disorders (DSM-IV-TR) - “homosexuality” absent Culture • early childhood traumas • propose a reparative therapy • based on psychoanalysis, group therapy, and spiritual help
