Reactivation of pulsatile GnRH secretion after childhood quiescence
Expansion
The hypothalamic GnRH pulse generator is active in fetal life and infancy (the so-called mini-puberty of the first 6 months), then suppressed throughout childhood, then reactivated at puberty.
Reactivation begins with nocturnal pulses of LH, which gradually extend through the day.
Permissive signals
- Kisspeptin neurones, now recognised as the key upstream regulator; loss of function mutations cause hypogonadotrophic hypogonadism
- Leptin, signalling adequate energy stores. This is why very low body fat from anorexia nervosa or intensive athletic training delays puberty and causes amenorrhoea, and why obesity is associated with earlier onset in girls
Adrenarche is separate and earlier: adrenal androgen production from about age 6 to 8, producing pubic and axillary hair and body odour, and independent of the gonadotrophin axis. Isolated adrenarche is therefore not true precocious puberty.
Precocious puberty is central (gonadotrophin dependent, treated with GnRH agonists to downregulate the axis) or peripheral (gonadotrophin independent, from gonadal or adrenal sources).