Submission Number: GAR-4-99-130

Abstract Number: 246

A GABA_B AGONIST REVERSES THE NEGATIVE FEEDBACK EFFECT OF TESTOSTERONE (T) ON LUTEINIZING HORMONE (LH) IN MALE SHEEP.

GL Jackson*, S Wood and D Kuehl

Dept of Veterinary Biosciences, University of Illinois, Urbana-Champaign, Illinois ¹

Abstract:
Infusion of baclofen (BAC), a GABA_B agonist, into the medial basal hypothalamus (MBH) of castrated rams rapidly increases LH pulse amplitude without altering pulse frequency. The objectives of this study were to determine if 1) T blocked this action of BAC, 2) the increase in LH pulse amplitude was due to increased GnRH pulse amplitude, 3) FSH secretion also was altered. In the first experiment, we tested the main effects and interaction of BAC and T on FSH and LH pulse patterns in castrated rams (n=6-7). Microdialysis guide cannulae were implanted bilaterally into the MBH. Following recovery of the animal from surgery, the MBH was perfused using concentric microdialysis probes (2 mm tip) with artificial cerebrospinal fluid (CSF) for a 3 h control period followed by either CSF or 1mM BAC for 4 h. Blood samples were taken at 10-min intervals. LH pulses were undetectable in some T-treated animals during the control period (mean 10.41.3 vs 3.31.3 ng/ml). The change (control period vs drug-infusion period) in mean LH was greater (P<0.01) in response to BAC than to CSF and was not altered by T. The BAC x T interaction was non-significant. Mean FSH was decreased by T (P<0.01), but was not altered by BAC. In the second experiment infusion of BAC into the MBH of intact males (n=2) resulted within 1 h in the onset of frequent and robust GnRH pulses (0.15/h pre-BAC vs 2/hr post-BAC) that were followed either immediately or gradually by coincident LH pulses. One interpretation is that BAC acts at two sites, both "downstream" of the site of action of T. At one site GABA_B receptors may regulate pulse amplitude in both the presence and absence of T, and at another may regulate pulse frequency by modulating the inhibitory effect of T. (Supported by USDA Grant AG 99-35203-7737.

Keywords: GABA, Testosterone, LH

This abstract is being presented at: 2:00 PM in session:
SESSION 12: NEUROENDOCRINOLOGY I