Transcript HM-for-Kamoha-

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
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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
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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
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•
•
•
•
•
•
•
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