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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020535-02
Application #
3318717
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Eastern Virginia Medical School
Department
Type
Schools of Medicine
DUNS #
City
Norfolk
State
VA
Country
United States
Zip Code
23501