This research seeks to describe the conditions whereby hypothalamic serotonergic terminals modulate the release of luteinizing hormone releasing hormone (LHRH) in both the intact and ovariectomized-estradiol-progesterone implanted rat (OVX-E2P). The following specific hypotheses will be tested using in vitro superfusion and in vivo push-pull perfusion (PPP) techniques. 1. The suprachiasmatic nucleus (SCN) is required for or greatly enhances LHRH output from the hypothalamus. 2. Photoperiod is a major determinant of changes in serotonergic metabolism and LHRH release. 3. Serotonin exerts significant effects on LHRH release from the hypothalamus. Primary attention will focus on the intact rat during proestrus and on the OVX-E2P rat as two models characterized by phasic activation of the luteinizing hormone (LH) release system. An in vitro superfusion system will be used to assess the effects of lesions, serotonergic drugs and photoperiod on LHRH release from the hypothalamus. An in vivo central nervous push-pull perfusion (PPP) system coupled to high pressure liquid chromatography with electrochemical detection (HPLC-EC) will be used to monitor the SCN or mediobasal hypothalamic (MBH) profile of serotonergic metabolism, while LHRH release will be estimated by radioimmunoassay (RIA). Selective and timely sampling of plasma LH via a chronic jugular cannula will permit temporal correlation of indole metabolism, LHRH, and LH secretion in a conscious, unrestrained rat and permit in vivo testing of pharmacological and photoperiod manipulations. These studies utilizing this new research model will result in improved knowledge in reproductive neuroendocrinology and may lead to new ideas for research in solving human neuroendocrine and reproductive problems in health and disease.
| Ramirez, A D; Ramirez, V D; Meyer, D C (1987) The nature and magnitude of in vivo 5-hydroxyindoleacetic acid output from 5-hydroxytryptamine terminals is related to specific regions of the suprachiasmatic nucleus. Neuroendocrinology 46:430-8 |
| Meyer, D C (1987) In-vitro pulsatile luteinizing hormone-releasing hormone output is dependent on hypothalamic region and the stage of the estrous cycle. Biol Reprod 37:1207-14 |
