Developmentally, the fetal GnRH pulse generator and its activation of the downstream gonadotrope and gonadal axis in humans is fully operational in both sexes by the end of the 1st trimester of gestation (Grumbach MM 1994). Subsequently, serum LH and FSH levels are suppressed and at the time of delivery are undetectable levels in umbilical cord blood, presumably secondary to the inhibitory effects of the pharmacological levels of placentallyderived sex steroids (Grumbach MM 1990; Massa, de Zegher et al. 1992) and possibly the high levels of circulating kisspeptin (Seminara, Dipietro et al. 2006; Ramaswamy, Seminara et al. 2007). Within minutes of birth, male infants exhibit a brief surge of LH and testosterone that persists for up to 12 hours (Corbier, Dehennin et al. 1990; de Zegher, Devlieger et al. 1992). In the subsequent 1–2 weeks of the neonatal period, the declining levels of placentally derived inhibitory factors then reveal a reawakened secretion of the hypothalamic GnRH pulse generator that results in the characteristic burst of GnRH-induced activity of the reproductive axis that is a hallmark of this period.

This neonatal burst of secretory activity of the hypothalamic-pituitary-gonadal axis, termed the “mini-puberty of infancy”(Fig 1), differs in its duration between the two sexes. In males, LH, FSH, and testosterone levels peak between 4–10 weeks following which GnRH quiescence eventually is complete by 6 months (Forest 1990; Andersson, Toppari et al. 1998). In contrast, female infants show longer persistence of their GnRH secretory activation of their reproductive axes' activity for up to 3 years, with hormonal values being highly variable during this time and characterized by an FSH predominance in striking contrast to the male (Waldhauser, Weissenbacher et al. 1981; Andersson, Toppari et al. 1998). In both sexes, this neonatal window of reproductive activation is driven by GnRH secretion and appears to serve at least two critical developmental agendas. In males, the first is a rapid expansion of the Sertoli cell population (Sharpe, Fraser et al. 2003; Sharpe, McKinnell et al. 2003) with a subsequent increase in the germ cell number that provides the underpinnings for subsequent fertility during adulthood (Muller and Skakkebaek 1984). The second is exposure of all sex steroid dependent target organs (especially the brain) to a key developmental period of adult levels of sex steroids. This exposure has important organizational consequences for both immediate and subsequent development such as