Effects of Selective Deletion of Tyrosine Hydroxylase from Kisspeptin Cells on Puberty and Reproduction in Male and Female Mice.

The neuropeptide kisspeptin, encoded by , regulates reproduction by stimulating GnRH secretion. syntheizing neurons reside primarily in the hypothalamic anteroventral periventricular (AVPV/PeN) and arcuate (ARC) nuclei. AVPV/PeN neurons are sexually dimorphic, with females expressing more than males, and participate in estradiol (E)-induced positive feedback control of GnRH secretion. In mice, most AVPV/PeN cells coexpress tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis (in this case, dopamine). Dopamine treatment can inhibit GnRH neurons, but the function of dopamine signaling arising specifically from AVPV/PeN cells is unknown. We generated a novel TH flox mouse and used Cre-Lox technology to selectively ablate specifically from cells. We then examined the effects of selective knock-out on puberty and reproduction in both sexes. In control mice, 90% of AVPV/PeN neurons coexpressed , whereas in mice lacking exclusively in cells (termed Kiss THKOs), was successfully absent from virtually all cells. Despite this absence of , both female and male Kiss THKOs displayed normal body weights, puberty onset, and basal gonadotropin levels in adulthood, although testosterone (T) was significantly elevated in adult male Kiss THKOs. The E-induced LH surge was unaffected in Kiss THKO females, and neuronal activation status of kisspeptin and GnRH cells was also normal. Supporting this, fertility and fecundity were normal in Kiss THKOs of both sexes. Thus, despite high colocalization of and in the AVPV/PeN, dopamine produced in these cells is not required for puberty or reproduction, and its function remains unknown.