Skip to main content
ENDO 2026 Main banner

Reproductive Endocrinology

SUN-124 - Mecp2 Regulates Puberty Onset Through Actions in the Reproductive Hub of the Hypothalamus

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT


Background:
Puberty is initiated by reactivation of pulsatile hypothalamic GnRH secretion, which is driven mainly by KNDy neurons that express kisspeptin, neurokinin B (encoded by Tac2), and dynorphin. Central precocious puberty (CPP) results from early reactivation of GnRH release, leading to premature development of secondary sexual characteristics. Human genetic studies have implicated mutations in Methyl-CpG-binding protein 2 (MECP2), an X-linked gene, in CPP. The mechanism by which MECP2 regulates puberty initiation remains to be fully elucidated. Weight is an important determinant for puberty onset. We previously showed that Mecp2 hemizygous (knockout) male mice (Mecp2–/y) reached puberty at a lower body weight (but later age) compared to wild type (WT) males, with no differences between heterozygous (Mecp2+/–) and WT females. We hypothesized that Mecp2 regulates hypothalamic factors critical for pubertal initiation.

Methods:
Adult Mecp2+/– female mice were bred with WT males. The posterior hypothalamus (PH) was isolated for RT-qPCR at postnatal day (PND) 10 (prepubertal) and PND29 (peripubertal). Expression of estrogen receptor 1 (Esr1), Esr2, dynorphin (Pdyn), Kiss1, Mecp2, makorin ring finger protein 3 (Mkrn3) and Tac2, genes important for puberty initiation in the PH, were assessed.
Immunohistochemistry was performed to assess colocalization of MeCP2 and GnRH in the preoptic area (POA) of male mice, and MeCP2 and neurokinin B (NKB) in the arcuate nucleus (ARC) of ovariectomized WT female mice.

Results:
At PND10, the expression of candidate target genes did not differ between experimental and control mice. At PND29, Kiss1 expression was significantly higher (approximately 2-fold) in Mecp2+/– vs WT females (P < 0.05) and Tac2 expression was lower (approximately 2-fold) in Mecp2−/y vs WT males (P < 0.05). Immunohistochemistry demonstrated colocalization of MeCP2 with GnRH in POA and with NKB in ARC.

Conclusions:
Kiss1 expression was increased in Mecp2+/– female mice; however, no alteration in pubertal timing was observed, confirming that a small amount of Kiss1 is sufficient to stimulate reproductive development. Although Mecp2−/y male mice had reduced Tac2 mRNA levels at PND29, these mice underwent pubertal maturation despite having lower body weight. The effects of the reduced Tac2 mRNA levels in these mice are not clear. Notably, the detection of MeCP2 in KNDy and GnRH neurons suggest its hypothalamic action in puberty regulation.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*