The Role of GABA in Reproductive Neuroendocrine Systems

Local gamma-amino butyric acid (GABA) neurons in the hypothalamus can modulate the luteinizing hormone releasing hormone (LHRH) pulse generating system. Two animal models (intact and ovariectomized rats) were used to determine the nature of modulation of LHRH release by GABA. The experiment determined the release of LHRH, serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) during two hormonal states with each model. In the intact rat the proestrus and estrus states were examined, and in the ovariectomized rat in-vitro release was determined with (OVX2) and without (OVX) estradiol treatment. In-vivo experiments studied the effect of stimulation of GABA receptors in the median eminence on LHRH and 5-HIAA release. The intact rat model released greater amounts of LHRH than the ovariectomized rat model. The proestrus hormonal state had more LHRH released than the estrus state; however, the activity of the serotonergic system was greater during estrus. The LHRH release in the ovariectomized rat model was similar during both hormonal states but serotonergic activity was greater in the OVXE2 rat. GABA stimulation did not change LHRH release although it did change serotonergic activity during the proestrus hormonal state. In the OVXE2 rat GABA stimulation decreased LHRH release, while serotonergic activity was not altered. None of the receptor subtype specific agonists and antagonists significantly increased or decreased LHRH and 5-HIAA release. The in-vivo experiments showed that GABA could decrease LHRH release from the median eminence, while muscimol could change 5-HIAA release