| First Author | Dubois SL | Year | 2015 |
| Journal | Endocrinology | Volume | 156 |
| Issue | 3 | Pages | 1111-20 |
| PubMed ID | 25545386 | Mgi Jnum | J:221928 |
| Mgi Id | MGI:5641841 | Doi | 10.1210/en.2014-1851 |
| Citation | Dubois SL, et al. (2015) Positive, but not negative feedback actions of estradiol in adult female mice require estrogen receptor alpha in kisspeptin neurons. Endocrinology 156(3):1111-20 |
| abstractText | Hypothalamic kisspeptin (Kiss1) neurons express estrogen receptor alpha (ERalpha) and exert control over GnRH/LH secretion in female rodents. It has been proposed that estradiol (E2) activation of ERalpha in kisspeptin neurons in the arcuate nucleus (ARC) suppresses GnRH/LH secretion (negative feedback), whereas E2 activation of ERalpha in kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) mediates the release of preovulatory GnRH/LH surges (positive feedback). To test these hypotheses, we generated mice bearing kisspeptin cell-specific deletion of ERalpha (KERalphaKO) and treated them with E2 regimens that evoke either negative or positive feedback actions on GnRH/LH secretion. Using negative feedback regimens, as expected, E2 effectively suppressed LH levels in ovariectomized (OVX) wild-type (WT) mice to the levels seen in ovary-intact mice. Surprisingly, however, despite the fact that E2 regulation of Kiss1 mRNA expression was abrogated in both the ARC and AVPV of KERalphaKO mice, E2 also effectively decreased LH levels in OVX KERalphaKO mice to the levels seen in ovary-intact mice. Conversely, using a positive feedback regimen, E2 stimulated LH surges in WT mice, but had no effect in KERalphaKO mice. These experiments clearly demonstrate that ERalpha in kisspeptin neurons is required for the positive, but not negative feedback actions of E2 on GnRH/LH secretion in adult female mice. It remains to be determined whether the failure of KERalphaKO mice to exhibit GnRH/LH surges reflects the role of ERalpha in the development of kisspeptin neurons, in the active signaling processes leading to the release of GnRH/LH surges, or both. |
