Role of galanin in stimulation of pituitary luteinizing hormone secretion as revealed by a specific receptor antagonist, galantide

In this study, a specific Galanin (GAL) receptor antagonist, galantide, was employed to evaluate the role of endogenous GAL in episodic basal and phasic LH release in rats. To assess the specificity of galantide, a series of experiments was performed. In the first experiment, we observed that administration of GAL (0.62 nm) intracerebroventricularly (icv) in ovarian steroid-primed ovariectomized (ovx) rats rapidly increased plasma LH levels between 10-30 min, and prior injection of galantide icv (5 nm) blocked the GAL-induced LH release. In the second experiment, galantide inhibited the GAL-evoked in vitro release of LHRH from the median eminence-arcuate nucleus (ME-ARC) of ovarian steroid-primed ovx rats. In addition, galantide on its own significantly decreased the basal efflux of LHRH from the ME-ARC of similarly treated rats, thereby suggesting that even the basal LHRH secretion may be a GAL-dependent event. In the third experiment, the effects of galantide on the phasic LH surge elicited by progesterone (P) in estradiol benzoate-primed ovx rats and that occurring spontaneously on proestrus were examined. Ovx rats bearing icv cannulae were primed with estradiol benzoate (30 micrograms/rat, sc) and 2 days later received a P (2 mg/rat, sc) injection at 1000 h to evoke a LH surge in the afternoon. Galantide (1 or 5 nm) in 3 microliters saline or saline was injected icv at 1300, 1400, and 1500 h. The results showed that the two dosages of galantide suppressed the LH surge in the afternoon. On the other hand, only a very high dose of galantide (15 nm) injected iv at 1300, 1400, and 1500 h blunted the P-induced LH hypersecretion. Central injections of galantide (1 or 5 nm) at 1300, 1400, and 1500 h on proestrus also inhibited the preovulatory LH surge and significantly reduced the numbers of rats ovulating the following day. In the final experiment, the role of GAL receptors in modulation of episodic LH release was analyzed in ovx rats. The results showed that an injection of galantide (5 nm, icv) significantly decreased both the mean LH levels and the amplitude of LH episodes during the 3-h observation period. Cumulatively, these results show that normally GAL stimulates LHRH release by activation of a specific receptor located in the ME-ARC, and that GAL may be a key excitatory signal in the hypothalamic neural circuitry involved in the regulation of basal episodic and phasic LHRH secretion in cycling female rats.(ABSTRACT TRUNCATED AT 400 WORDS)