Quantitative and temporal aspects of serotonin's facilitatory action on phasic secretion of luteinizing hormone in female rats.

Abstract

The purpose of this study was to determine if the circadian rhythm in hypothalamic serotonin (5HT) contributes to the facilitatory effect of the amine upon estrogen-induced luteinizing hormone (LH) surges in ovariectomized rats. p-Chlorophenylalanine (pCPA; 250 mg/kg) blocked 5HT synthesis, reduced its content and abolished its circadian rhythm in the hypothalamus. 5-Hydroxytryptophan (5HTP; 100 mg/kg) administered with pargyline (75 mg/kg), a monoamine oxidase inhibitor, stimulated 5HT synthesis, increased its levels and also eliminated daily changes in hypothalamic 5HT. Thus, drugs with opposite effects on 5HT synthesis had the same effect on the hypothalamic 5HT circadian rhythm. Besides blocking daily changes in 5HT, pCPA and 5HTP also blocked LH surges in ovariectomized rats receiving estrogen supplements. On the other hand, both circadian rhythms were reinstated when pCPA-treated rats were also given 5HTP, i.e., 5HTP which was initially inhibitory, became facilitatory to LH surges in rats pretreated with pCPA. These findings suggest that the amount of hypothalamic 5HT as well as its metabolic pattern are important to the facilitatory effect of 5HT on phasic LH secretion. To test this hypothesis further, 5HTP was given in lower doses (50 mg/kg) and without pargyline, in order to attenuate rather than obliterate the hypothalamic 5HT rhythm. Injections of 5HTP at 18.00 h and 12 h later at 06.00 h reduced the daily fluctuations in hypothalamic 5HT content and also attenuated estrogen-induced LH surges. When increasing doses of 5HTP were used to enhance hypothalamic 5HT content, an inverse correlation (p