Differential regulation of luteinizing hormone release by gamma-aminobutyric acid receptor subtypes in the arcuate-ventromedial region of the castrated ram.
We investigated the effects on LH secretion of infusing gamma-aminobutyric acid (GABA) agonists muscimol and baclofen (GABAA and GABAB receptor agonists, respectively) into either the medial preoptic area (mPOA) or the arcuate-ventromedial region (ARC-VMR) of the hypothalamus of castrated rams during the nonbreeding season. Bilateral microdialysis of artificial cerebrospinal fluid for 4 h followed by treatment with artificial cerebrospinal fluid, baclofen (1 mM), or muscimol (1 mM in the ARC-VMR, 250 microM in the mPOA) for 4 h was carried out on three separate occasions in random order. Simultaneously, jugular venous blood was collected at 10-min intervals, and plasma later was assayed for LH. The estimated dose of baclofen delivered to each unilateral microdialysis site was 7.9 micrograms; for muscimol, it was 1.1 micrograms for the mPOA and 4.5 micrograms for the ARC-VMR. In the mPOA, baclofen had no detectable effect, whereas muscimol had a delayed suppressive effect on mean LH (P < 0.01). In the ARC-VMR muscimol rapidly reduced mean LH (P < 0.01). In contrast, baclofen increased mean LH (P = 0.01) and LH pulse amplitude (P = 0.05) without altering the LH interpulse interval (P > 0.10). These results support the involvement of GABAA receptors in the mPOA in regulating LH secretory patterns. More importantly, both GABAA and GABA(B) receptors in the ARC-VMR appear to differentially modulate LH and, presumably, GnRH release. Whether GABA acts directly on the GnRH neuron or indirectly through other neural systems remains to be determined.
Ferreira
S A
SA
Department of Veterinary Biosciences, University of Illinois, Urbana 61801, USA.
Scott
C J
CJ
Kuehl
D E
DE
Jackson
G L
GL
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology*; D001418:Baclofen / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D017551:Microdialysis; D009118:Muscimol / Q000494:pharmacology; D009919:Orchiectomy; D011301:Preoptic Area / Q000502:physiology; D018079:Receptors, GABA / Q000502:physiology*; D012756:Sheep; D014697:Ventromedial Hypothalamic Nucleus / Q000502:physiology*
D018079:Receptors, GABA; D009118:Muscimol; D007986:Luteinizing Hormone; D001418:Baclofen