| First Author | Greenwald-Yarnell ML | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 4 | Pages | 1555-65 |
| PubMed ID | 26862996 | Mgi Jnum | J:234023 |
| Mgi Id | MGI:5788800 | Doi | 10.1210/en.2015-1928 |
| Citation | Greenwald-Yarnell ML, et al. (2016) ERalpha in Tac2 Neurons Regulates Puberty Onset in Female Mice. Endocrinology 157(4):1555-65 |
| abstractText | A variety of data suggest that estrogen action on kisspeptin (Kiss1)-containing arcuate nucleus neurons (which coexpress Kiss1, neurokinin B (the product of Tac2) and dynorphin (KNDy) neurons restrains reproductive onset and function, but roles for estrogen action in these Kiss1 neurons relative to a distinct population of rostral hypothalamic Kiss1 neurons (which does not express Tac2 or dynorphin) have not been directly tested. To test the role for estrogen receptor (ER)alpha in KNDy cells, we thus generated Tac2(Cre) and Kiss1(Cre) knock-in mice and bred them onto the Esr1(flox) background to ablate ERalpha specifically in Tac2-expressing cells (ERalpha(Tac2)KO mice) or all Kiss1 cells (ERalpha(Kiss1)KO mice), respectively. Most ERalpha-expressing Tac2 neurons represent KNDy cells. Arcuate nucleus Kiss1 expression was elevated in ERalpha(Tac2)KO and ERalpha(Kiss1)KO females independent of gonadal hormones, whereas rostral hypothalamic Kiss1 expression was normal in ERalpha(Tac2)KO but decreased in ERalpha(Kiss1)KO females; this suggests that ERalpha in rostral Kiss1 cells is crucial for control of Kiss1 expression in these cells. Both ERalpha(Kiss1)KO and ERalpha(Tac2)KO females displayed early vaginal opening, early and persistent vaginal cornification, increased gonadotropins, uterine hypertrophy, and other evidence of estrogen excess. Thus, deletion of ERalpha in Tac2 neurons suffices to drive precocious gonadal hyperstimulation, demonstrating that ERalpha in Tac2 neurons typically restrains pubertal onset and hypothalamic reproductive drive. |
