Enhancement of a robust arcuate GABAergic input to gonadotropin-releasing hormone neurons in a model of polycystic ovarian syndrome
Abstract
Polycystic ovarian syndrome (PCOS) is the leading cause of anovulatory infertility. Although the etiology of PCOS is unclear, disrupted central mechanisms mediating steroid hormone feedback to gonadotropin-releasing hormone (GnRH) neurons have been suggested. We describe here, in a mouse model reflecting the clinical neuroendocrine phenotype of PCOS, evidence for disordered progesterone (P4)-sensitive GABAergic input to GnRH neurons, originating specifically within the arcuate nucleus. These discoveries define a previously unidentified neuronal pathway, potentially critical for the steroid hormone feedback control of fertility. Of clinical relevance, our findings help explain the impact of GABA agonist drugs on menstrual cycle irregularity and interference with oral contraceptives and could be the basis for understanding clinical therapies of PCOS.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- January 2015
- DOI:
- 10.1073/pnas.1415038112
- Bibcode:
- 2015PNAS..112..596M