OBJECTIVE: Due to conflicting observations from previous investigations, the role of serotonin (5-HT) in the regulation of the human menstrual cycle has not been clearly established. We have therefore investigated the possible participation of 5-HR in the control of gonadotrophin and PRL secretion in women, using the potent 5-HT3 receptor antagonist ondansetron as a pharmacological probe. DESIGN: Serum profiles of LH, FSH and PRL were obtained in 9 normally cycling women during a control and a treatment cycle, during which ondansetron (8 mg orally) was administered daily. On day 10 of both cycles, the serum pulsatility of LH, FSH and PRL was assessed by frequent blood sampling (at 10-minute intervals for 10 hours). Pituitary responsiveness was tested by administration of a GnRH bolus (25 micrograms i.v. after 8 hours). MEASUREMENTS: LH, FSH and PRL were serially determined in all blood samples by immunofluorescence assays. The resulting hormone data arrays were searched for significant fluctuations by the Cluster pulse algorithm. RESULTS: Compared with control cycles, the temporal organization and the endocrine characteristics of the treatment cycles remained virtually unaltered. Serotonin antagonism did not noticeably affect the LH pulse attributes (frequencies, interpulse intervals, amplitudes). Although FSH amplitudes declined markedly (P < 0.05), the remaining pulse attributes were unchanged. A clear increase (P < 0.05) in the PRL pulse frequency was noted, while PRL pulse amplitudes tended to increase (P = 0.1). Gonadotrophin and PRL release in response to GnRH administration was unaltered by ondansetron treatment. CONCLUSIONS: Serotoninergic blockade by a selective 5-HT3 receptor antagonist failed to modify pulsatile LH secretion, but induced distinct changes in episodic FSH and PRL secretion. Since the pituitary gonadotrophin and PRL responsiveness remained unaltered during 5-HT3 receptor blockade, the observed alterations in the FSH and PRL secretion presumably relate to altered hypothalamic regulation of these pituitary hormones. Thus, the central regulation of pulsatile FSH and PRL release in women appears to involve 5-HT3 receptor-mediated processes.
OBJECTIVE: Due to conflicting observations from previous investigations, the role of serotonin (5-HT) in the regulation of the human menstrual cycle has not been clearly established. We have therefore investigated the possible participation of 5-HR in the control of gonadotrophin and PRL secretion in women, using the potent 5-HT3 receptor antagonist ondansetron as a pharmacological probe. DESIGN: Serum profiles of LH, FSH and PRL were obtained in 9 normally cycling women during a control and a treatment cycle, during which ondansetron (8 mg orally) was administered daily. On day 10 of both cycles, the serum pulsatility of LH, FSH and PRL was assessed by frequent blood sampling (at 10-minute intervals for 10 hours). Pituitary responsiveness was tested by administration of a GnRH bolus (25 micrograms i.v. after 8 hours). MEASUREMENTS: LH, FSH and PRL were serially determined in all blood samples by immunofluorescence assays. The resulting hormone data arrays were searched for significant fluctuations by the Cluster pulse algorithm. RESULTS: Compared with control cycles, the temporal organization and the endocrine characteristics of the treatment cycles remained virtually unaltered. Serotonin antagonism did not noticeably affect the LH pulse attributes (frequencies, interpulse intervals, amplitudes). Although FSH amplitudes declined markedly (P < 0.05), the remaining pulse attributes were unchanged. A clear increase (P < 0.05) in the PRL pulse frequency was noted, while PRL pulse amplitudes tended to increase (P = 0.1). Gonadotrophin and PRL release in response to GnRH administration was unaltered by ondansetron treatment. CONCLUSIONS: Serotoninergic blockade by a selective 5-HT3 receptor antagonist failed to modify pulsatile LH secretion, but induced distinct changes in episodic FSH and PRL secretion. Since the pituitary gonadotrophin and PRL responsiveness remained unaltered during 5-HT3 receptor blockade, the observed alterations in the FSH and PRL secretion presumably relate to altered hypothalamic regulation of these pituitary hormones. Thus, the central regulation of pulsatile FSH and PRL release in women appears to involve 5-HT3 receptor-mediated processes.