| First Author | Wang L | Year | 2018 |
| Journal | J Neurosci | Volume | 38 |
| Issue | 5 | Pages | 1061-1072 |
| PubMed ID | 29114074 | Mgi Jnum | J:257555 |
| Mgi Id | MGI:6115398 | Doi | 10.1523/JNEUROSCI.2428-17.2017 |
| Citation | Wang L, et al. (2018) Glutamatergic Transmission to Hypothalamic Kisspeptin Neurons Is Differentially Regulated by Estradiol through Estrogen Receptor alpha in Adult Female Mice. J Neurosci 38(5):1061-1072 |
| abstractText | Estradiol feedback regulates gonadotropin-releasing hormone (GnRH) neurons and subsequent luteinizing hormone (LH) release. Estradiol acts via estrogen receptor alpha (ERalpha)-expressing afferents of GnRH neurons, including kisspeptin neurons in the anteroventral periventricular (AVPV) and arcuate nuclei, providing homeostatic feedback on episodic GnRH/LH release as well as positive feedback to control ovulation. Ionotropic glutamate receptors are important for estradiol feedback, but it is not known where they fit in the circuitry. Estradiol-negative feedback decreased glutamatergic transmission to AVPV and increased it to arcuate kisspeptin neurons; positive feedback had the opposite effect. Deletion of ERalpha in kisspeptin cells decreased glutamate transmission to AVPV neurons and markedly increased it to arcuate kisspeptin neurons, which also exhibited increased spontaneous firing rate. KERKO mice had increased LH pulse frequency, indicating loss of negative feedback. These observations indicate that ERalpha in kisspeptin cells is required for appropriate differential regulation of these neurons and neuroendocrine output by estradiol.SIGNIFICANCE STATEMENT The brain regulates fertility through gonadotropin-releasing hormone (GnRH) neurons. Ovarian estradiol regulates the pattern of GnRH (negative feedback) and initiates a surge of release that triggers ovulation (positive feedback). GnRH neurons do not express the estrogen receptor needed for feedback (estrogen receptor alpha [ERalpha]); kisspeptin neurons in the arcuate and anteroventral periventricular nuclei are postulated to mediate negative and positive feedback, respectively. Here we extend the network through which feedback is mediated by demonstrating that glutamatergic transmission to these kisspeptin populations is differentially regulated during the reproductive cycle and by estradiol. Electrophysiological and in vivo hormone profile experiments on kisspeptin-specific ERalpha knock-out mice demonstrate that ERalpha in kisspeptin cells is required for appropriate differential regulation of these neurons and for neuroendocrine output. |
