Quantitative and Temporal Aspects of Serotonin’s Facilitatory Action on Phasic Secretion of Luteinizing Hormone in Female Rats

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 < 0.01) with serum LH content was observed over the range 5 kg–100 mg/kg 5HTP. The effect of progesterone upon daily changes in hypothalamic 5HT was also determined. When administered at 10.00 h, progesterone significantly potentiated (p < 0.01) phasic secretion of LH and also increased (p < 0.05) peak, but not baseline, hypothalamic 5HT levels, thus amplifying the neurotransmitter’s circadian rhythm. Furthermore, when 5HTP was given 1 h before progesterone, the onset of phasic LH secretion was advanced. This change in the timing of phasic LH secretion was associated with early accumulation of 5HT in the hypothalamus. Hypothalamic 5HT turnover was increased by 5HTP treatment in rats made supersensitive to 5HT stimulation, and LH surges were also potentiated under these conditions. The results of this study suggest that the daily pattern of hypothalamic 5HT metabolism influences the pattern of LH secretion during the estrogen-positive feedback response. Since the size of LH surges correlates with daily fluctuations in hypothalamic 5HT, then a facilitatory signal whose intensity is related to the magnitude of these daily changes may be generated during the post-acrophase component of the 5HT circadian rhythm.