are in agreement with the identification of a loss-of-function mutation in patients with central precocious puberty, corroborating the view that the mutation has an inhibitory effect on the secretion of GnRH. The initiation of puberty is thought to result from a decrease in factors that inhibit the release of GnRH combined with an increase in stimulatory factors. Studies of hypogonadotropic hypogonadism have led to the identification of genes encoding factors that have stimulatory input.12,13 In contrast, MKRN3 seems to have an inhibitory role in humans.
