OBJECTIVES: The hypothalamus possesses serotoninergic fibres which arise from neuronal cell bodies located in the raphe nuclei and have synapse on GnRH-secreting neurones. Hitherto, no firm evidence has been produced to support a role for serotoninergic control of LH in humans. Our first objective was to investigate whether pulsatile administration of L-5-hydroxytryptophan--the immediate precursor of serotonin--affects pulsatile LH secretion in the medium-late follicular phase of normal women. Since the results of the first experiment suggest that L-5-hydroxytryptophan amplifies LH release, our second objective was to investigate whether, in the absence of GnRH, L-5-hydroxytryptophan can release LH. This was done by studying LH response in patients with hypogonadotrophic hypogonadism of hypothalamic origin. PATIENTS: Twenty-two normal women (18-25 years old) and 8 patients with hypogonadotrophic hypogonadism (2 men with Kallmann's syndrome and 6 women with anorexia nervosa). DESIGN: Serum LH levels in the 22 subjects (reference population) were monitored at 10-minute intervals over an 8-hour period (1000-1800h) during medium-late follicular phase. In 7 of these subjects, serum LH levels were monitored in their next medium-late follicular phase while L-5-hydroxytryptophan was administered at hourly intervals from 1000 to 1800 h; the peripheral conversion of L-5-hydroxytryptophan to serotonin was inhibited by 150 mg of benserazide at 0930 and 1430h. To investigate whether, in the absence of GnRH, L-5-hydroxytryptophan can release LH, two patients with Kallmann's syndrome were monitored over a 7-hour period and 6 patients with anorexia nervosa over a 9-hour period. After a 2-5 hour control period the subjects received 150 mg of benserazide, and pulsatile L-5-hydroxytryptophan (every 30 minutes in the Kallmann's patients and every 45 minutes in the subjects with anorexia nervosa). MEASUREMENTS: LH pulses were identified and analysed according to number, amplitude, interpulse interval and pulse duration. RESULTS: In the normal women, L-5-hydroxytryptophan increased pulse amplitude (mean +/- SD; 3.02 +/- 1.42 IU/l vs. 1.75 +/- 0.98 IU/l before L-5-hydroxytryptophan and 1.90 +/- 1.04 IU/l in the reference population; P < 0.01 in both cases), but had no significant effects on pulse duration, interpulse interval or number of pulses. L-5-hydroxytryptophan had no effect on LH in patients with Kallmann's syndrome. In the anorexia nervosa group, the mean serum LH level increased significantly after L-5-hydroxytryptophan (3.90 +/- 2.46 IU/l vs. 3.06 +/- 1.23 IU/l, P < 0.001) but, as in Kallmann's patients, the three women in this group without residual LH pulsatility did not respond to L-5-hydroxytryptophan. CONCLUSION: Pulsatile administration of L-5-hydroxytryptophan increases LH pulse amplitude in the follicular phase of normal women. In the absence of GnRH, L-5-hydroxytryptophan does not stimulate pituitary LH secretion.
OBJECTIVES: The hypothalamus possesses serotoninergic fibres which arise from neuronal cell bodies located in the raphe nuclei and have synapse on GnRH-secreting neurones. Hitherto, no firm evidence has been produced to support a role for serotoninergic control of LH in humans. Our first objective was to investigate whether pulsatile administration of L-5-hydroxytryptophan--the immediate precursor of serotonin--affects pulsatile LH secretion in the medium-late follicular phase of normal women. Since the results of the first experiment suggest that L-5-hydroxytryptophan amplifies LH release, our second objective was to investigate whether, in the absence of GnRH, L-5-hydroxytryptophan can release LH. This was done by studying LH response in patients with hypogonadotrophic hypogonadism of hypothalamic origin. PATIENTS: Twenty-two normal women (18-25 years old) and 8 patients with hypogonadotrophic hypogonadism (2 men with Kallmann's syndrome and 6 women with anorexia nervosa). DESIGN: Serum LH levels in the 22 subjects (reference population) were monitored at 10-minute intervals over an 8-hour period (1000-1800h) during medium-late follicular phase. In 7 of these subjects, serum LH levels were monitored in their next medium-late follicular phase while L-5-hydroxytryptophan was administered at hourly intervals from 1000 to 1800 h; the peripheral conversion of L-5-hydroxytryptophan to serotonin was inhibited by 150 mg of benserazide at 0930 and 1430h. To investigate whether, in the absence of GnRH, L-5-hydroxytryptophan can release LH, two patients with Kallmann's syndrome were monitored over a 7-hour period and 6 patients with anorexia nervosa over a 9-hour period. After a 2-5 hour control period the subjects received 150 mg of benserazide, and pulsatile L-5-hydroxytryptophan (every 30 minutes in the Kallmann'spatients and every 45 minutes in the subjects with anorexia nervosa). MEASUREMENTS: LH pulses were identified and analysed according to number, amplitude, interpulse interval and pulse duration. RESULTS: In the normal women, L-5-hydroxytryptophan increased pulse amplitude (mean +/- SD; 3.02 +/- 1.42 IU/l vs. 1.75 +/- 0.98 IU/l before L-5-hydroxytryptophan and 1.90 +/- 1.04 IU/l in the reference population; P < 0.01 in both cases), but had no significant effects on pulse duration, interpulse interval or number of pulses. L-5-hydroxytryptophan had no effect on LH in patients with Kallmann's syndrome. In the anorexia nervosa group, the mean serum LH level increased significantly after L-5-hydroxytryptophan (3.90 +/- 2.46 IU/l vs. 3.06 +/- 1.23 IU/l, P < 0.001) but, as in Kallmann'spatients, the three women in this group without residual LH pulsatility did not respond to L-5-hydroxytryptophan. CONCLUSION: Pulsatile administration of L-5-hydroxytryptophan increases LH pulse amplitude in the follicular phase of normal women. In the absence of GnRH, L-5-hydroxytryptophan does not stimulate pituitary LH secretion.