title: L-hydroxytryptophan amplifies pulsatile secretion of LH in the follicular phase of normal women.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Endocrinology and Nutrition Service, Galician General Hospital, Santiago de Compostela School of Medicine, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Lado-Abeal
authors.forename: C
authors.initials: C
authors.lastname: Rey
authors.forename: J M
authors.initials: JM
authors.lastname: Cabezas-Agricola
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez
authors.forename: E
authors.initials: E
authors.lastname: Camarero
authors.forename: J
authors.initials: J
authors.lastname: Cabezas-Cerrato
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000856:Anorexia Nervosa / Q000503:physiopathology; D001545:Benserazide / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D005260:Female; D005498:Follicular Phase / Q000187:drug effects*; D006801:Humans; D007006:Hypogonadism / Q000503:physiopathology*; D017436:Kallmann Syndrome / Q000503:physiopathology; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical
chemical_list: D015259:Dopamine Agents; D001545:Benserazide; D007986:Luteinizing Hormone; D006916:5-Hydroxytryptophan