The central nervous system regulates gonadotropin secretion and maintains reproductive cycles through pulsatile release of luteinizing hormone-releasing hormone (LHRH). The decapeptide is released into hypophysial portal vessels and conveyed to the anterior pituitary to regulate LH secretion. The amplitude and frequency of LHRH pulses are influenced, in turn, by feedback actions of circulating gonadal steroids. The objective of the proposed studies is to gain a more complete, integrated understanding of regulatory mechanisms which govern three critical functions of LHRH neurons - LHRH synthesis, LHRH release, and LHRH actions. In vivo radiolabeling will be used to estimate rates of LHRH synthesis, microdialysis will be utilized to measure in vivo LHRH release patterns, and an in vivo isolated pituitary paradigm will be employed to analyze physiological actions of LHRH. These methods will be used to test hypotheses that (1) ovarian steroids directly or indirectly accelerate LHRH biosynthesis, leading to an increase in LHRH pulse amplitude and initiation of the preovulatory LH surge, and (2) homeostatic suppression of LH secretion at other times is manifest, in part, by restraint of LHRH pulse frequency. Microdialysis will also be used to test the hypothesis that catecholamine and endogenous opioid peptide neurons mediate steroid feedback actions. A RCDA is requested to facilitate acquisition of the scientific and technical expertise required in the proposed studies. The applicant, Dr. Jon E. Levine, (Assistant Professor of Neurobiology and Physiology at Northwestern University) is a neuroendocrinologist whose outstanding research potential has already been established through innovative work in developing methods for study of in vivo neuropeptide release. With RCDA support, the candidate's teaching and administrative responsibilities will be reduced, enabling the following short-term career goals to be realized: (1) rapid progress in the proposed studies, (2) training and consultation in biochemical procedures with Dr. Jeffery McKelvy (Head, Neuroscience Research Division, Abbot Laboratories) and with Dr. Ka- Leung Ngai (Director, Biotechnology Center, Northwestern University) and (3) increased scientific interactions with reproductive biologist northwestern University. A long-term goal of the candidate is to fully understand the inter-and intracellular mechanisms by which neural and endocrine factors regulate LHRH neurons. Such knowledge may help in development of contraceptive strategies, and aid in treatment of reproductive disorders, such as hypothalamic amenorhea.
| Porkka-Heiskanen, T; Urban, J H; Turek, F W et al. (1994) Gene expression in a subpopulation of luteinizing hormone-releasing hormone (LHRH) neurons prior to the preovulatory gonadotropin surge. J Neurosci 14:5548-58 |
| Bauer-Dantoin, A C; McDonald, J K; Levine, J E (1992) Neuropeptide Y potentiates luteinizing hormone (LH)-releasing hormone-induced LH secretion only under conditions leading to preovulatory LH surges. Endocrinology 131:2946-52 |
| Meredith, J M; Levine, J E (1992) Effects of castration on LH-RH patterns in intrahypophysial microdialysates. Brain Res 571:181-8 |
| Bauer-Dantoin, A C; McDonald, J K; Levine, J E (1991) Neuropeptide Y potentiates luteinizing hormone (LH)-releasing hormone-stimulated LH surges in pentobarbital-blocked proestrous rats. Endocrinology 129:402-8 |
