Role of 5-hydroxytryptamine receptors on luteinizing-hormone-releasing hormone release in the ovariectomized, estradiol-treated rat

Abstract

The present experiments examined the effect of ketanserin [5-hydroxytryptamine-2 (5-HT 2) antagonist] and 8-hydroxy-2-(di- n-propylamino) tetralin (8-OH-DPAT) (5-HT 1 agonist) on the in vitro release of luteinizing-hormone-releasing hormone (LHRH) from the medial basal hypothalamuspreoptic area-suprachiasmatic nucleus region (MBH-POA-SCN) of ovariectomized (OVX), estradiol-(E 2) treated rats using in vitro superfusion techniques. Regularly cycling female Holtzman rats (250–300 g) were maintained on a photoperiod of 0500–1900 h light at 22 ± 2° C. Rats were ovariectomized (25–30 days) and received Silastic E 2 implants (150 μg E 2/ml sesame oil) SC 48 h prior to the in vitro superfusion. Following a control period of Krebs-Ringer Phosphate (KRP) superfusion, ketanserin (5HT 2 receptor antagonist, 1 × 10 −6 M) significantly increased LHRH release ( p < 0.05). Subsequent superfusion of 5-HT (1 × 10 −8 M) significantly decreased ( p < 0.05) the effect of ketanserin on LHRH release. The 5-HT 2 antagonist Lilly 53857 (1 × 10 −6 M or 1 × 10 −5 M) did not increase LHRH release above control levels. Neither 5-HT nor quipazine had a significant effect on LHRH release at 1 × 10 −6 M. Superfusion of 8-OH-DPAT (5-HT 1 receptor agonist 1 × 10 −5 M) significantly ( p < 0.01) increased LHRH release but subsequent superfusion of 8-OH-DPAT + pindolol (mixed 5-HT 1a,1b and a β-adrenergic receptor antagonist, 1 × 10 −6 M) or pindolol alone had no effect on LHRH release. These results suggest that the 5-HT 1 receptor plays a role in LHRH release and this effect may be related to the opposing effects of postsynaptic and autoreceptors. However, the failure of Lilly 53857 to reproduce the stimulatory effect of ketanserin on LHRH release suggests that 5-HT 2 receptors in the MBH-POASCN may not modify LH release during the estrous cycle.