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

The present experiments examined the effect of ketanserin [5-hydroxytryptamine-2 (5-HT2) antagonist] and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (5-HT1 agonist) on the in vitro release of luteinizing-hormone-releasing hormone (LHRH) from the medial basal hypothalamus-preoptic area-suprachiasmatic nucleus region (MBH-POA-SCN) of ovariectomized (OVX), estradiol-(E2) 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 degrees C. Rats were ovariectomized (25-30 days) and received Silastic E2 implants (150 micrograms E2/ml sesame oil) SC 48 h prior to the in vitro superfusion. Following a control period of Krebs-Ringer Phosphate (KRP) superfusion, ketanserin (5-HT2 receptor antagonist, 1 x 10(-6) M) significantly increased LHRH release (p less than 0.05). Subsequent superfusion of 5-HT (1 x 10(-8) M) significantly decreased (p less than 0.05) the effect of ketanserin on LHRH release. The 5-HT2 antagonist Lilly 53857 (1 x 10(-6) M or 1 x 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 x 10(-6) M. Superfusion of 8-OH-DPAT (5-HT1 receptor agonist 1 x 10(-5) M) significantly (p less than 0.01) increased LHRH release but subsequent superfusion of 8-OH-DPAT + pindolol (mixed 5-HT1a,1b and a beta-adrenergic receptor antagonist, 1 x 10(-6) M) or pindolol alone had no effect on LHRH release. These results suggest that the 5-HT1 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-HT2 receptors in the MBH-POA-SCN may not modify LH release during the estrous cycle.