| First Author | Yeo SH | Year | 2014 |
| Journal | Endocrinology | Volume | 155 |
| Issue | 8 | Pages | 2986-95 |
| PubMed ID | 24905671 | Mgi Jnum | J:214453 |
| Mgi Id | MGI:5603001 | Doi | 10.1210/en.2014-1128 |
| Citation | Yeo SH, et al. (2014) Estrogen-negative feedback and estrous cyclicity are critically dependent upon estrogen receptor-alpha expression in the arcuate nucleus of adult female mice. Endocrinology 155(8):2986-95 |
| abstractText | The location and characteristics of cells within the brain that suppress GnRH neuron activity to contribute to the estrogen-negative feedback mechanism are poorly understood. Using adeno-associated virus (AAV)-mediated Cre-LoxP recombination in estrogen receptor-alpha (ERalpha) floxed mice (ERalpha(flox/flox)), we aimed to examine the role of ERalpha-expressing neurons located in the arcuate nucleus (ARN) in the estrogen-negative feedback mechanism. Bilateral injection of AAV-Cre into the ARN of ERalpha(flox/flox) mice (n = 14) resulted in the time-dependent ablation of up to 99% of ERalpha-immunoreactive cell numbers throughout the rostrocaudal length of the ARN. These mice were all acyclic by 5 weeks after AAV-Cre injections with most mice in constant estrous. Control wild-type mice injected with AAV-Cre (n = 13) were normal. Body weight was not altered in ERalpha(flox/flox) mice. After ovariectomy, a significant increment in LH secretion was observed in all genotypes, although its magnitude was reduced in ERalpha(flox/flox) mice. Acute and chronic estrogen-negative feedback were assessed by administering 17beta-estradiol to mice as a bolus (LH measured 3 h later) or SILASTIC brand capsule implant (LH measured 5 d later). This demonstrated that chronic estrogen feedback was absent in ERalpha(flox/flox) mice, whereas the acute feedback was normal. These results reveal a critical role for ERalpha-expressing cells within the ARN in both estrous cyclicity and the chronic estrogen negative feedback mechanism in female mice. This suggests that ARN cells provide a key indirect, transsynpatic route through which estradiol suppresses the activity of GnRH neurons. |
