L-5-hydroxytryptophan does not stimulate LH secretion directly from the pituitary in patients with gonadotrophin releasing hormone deficiency

• Published in: Clinical endocrinology (Oxford) Vol. 49; no. 2; pp. 203 - 207
• Main Authors: Lado-Abeal, Joaquin, Graña, Maria, Rey, Carlos, Cabezas-Cerrato, Jose
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.08.1998; Blackwell; Wiley Subscription Services, Inc
• Subjects: 5-Hydroxytryptophan - therapeutic use; Adult; Aromatic Amino Acid Decarboxylase Inhibitors; Biological and medical sciences; Carbidopa - therapeutic use; Drug Administration Schedule; Drug Therapy, Combination; Enzyme Inhibitors - therapeutic use; Female; Functional investigation of endocrine glands and genital system; Gonadotropin-Releasing Hormone - deficiency; Gonadotropin-Releasing Hormone - therapeutic use; Humans; Hypogonadism - drug therapy; Hypogonadism - physiopathology; Hypothalamic Diseases - drug therapy; Hypothalamic Diseases - physiopathology; Hypothalamus - drug effects; Hypothalamus - physiopathology; Investigative techniques, diagnostic techniques (general aspects); Luteinizing Hormone - metabolism; Male; Medical sciences; Pituitary Gland - drug effects; Pituitary Gland - physiopathology; Secretory Rate - drug effects; Europe; Spain; Endocrinopathy; Hypogonadotropic hypogonadism; Replacement therapy; Carbidopa; Hypothalamic diseases; Peptide hormone; Gonadotropin RH; Lyases; Glycoprotein hormone; Genital diseases; Blood plasma; Carboxy-lyases; Adult; Hormonal investigation; Hormone releasing factor; Human; Decarboxylase; Pathophysiology; Enzyme; Treatment efficiency; Enzyme inhibitor; Gonadotropin; Antiparkinson agent; Hypothalamic hormone; Carbon-carbon lyases; Chemotherapy; Adenohypophyseal hormone; Combined treatment; LH
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1046/j.1365-2265.1998.00501.x

OBJECTIVE There is abundant histological and physiological evidence that serotonin plays a role in the regulation of LH secretion in rats. Studies in human subjects have been few, but their results include the finding that pulsatile administration of L‐5‐hydroxytryptophan (5‐HTP, the immediate precursor of serotonin) amplifies LH secretion in women in the medium‐late follicular phase, and that this effect is not due to 5‐HTP directly inducing LH secretion by the pituitary. We have investigated whether 5‐HTP amplifies LH secretion by enhancing the response of the pituitary to GnRH. PATIENTS Seven patients aged 20–40 years with hypogonadotrophic hypogonadism (HH) of hypothalamic origin (3 men with Kallmann's syndrome, 2 women without anosmia and with GH deficiency, and 2 women with anorexia nervosa). DESIGN To prime the pituitary, subcutaneous pulsatile GnRH was administered for 7 days at the rate of one 5–20 μg pulse every 90 min. The day before the investigation, this regimen was replaced by 1.5–3 μg intravenous pulses at the same frequency. On the day of the investigation, 3 ml blood samples were taken every 10 min from 0850 to 19.00 hours. After the first two samples, the intravenous GnRH pulse frequency was increased to one per hour and was maintained at this level throughout the rest of the study. The first 4 h of the study acted as a control phase allowing determination of the pituitary response to GnRH. At 1300 h, 75 mg of the aromatic‐L‐amino‐acid decarboxylase inhibitor carbidopa was administered orally; carbidopa does not cross the blood–brain barrier, and prevents peripheral conversion of 5‐HTP to serotonin. At 1600 h, another 75 mg dose of carbidopa was administered, and administration of 8–20 mg pulses of 5‐HTP at a rate of one pulse per hour was begun. MEASUREMENTS LH was determined in triplicate by an immunoradiometric assay (IRMA), and LH pulses identified by means of a program developed in our laboratory. RESULTS When pulsatile administration of GnRH was accompanied by administration of carbidopa and 5‐HTP, LH pulse amplitude (2.32 ± 0.71 IU/l) did not differ significantly from its value in either the GnRH + carbidopa phase (2.58 ± 1.12 IU/l) or the unaccompanied GnRH phase (2.77 ± 1.76 IU/l). CONCLUSIONS L‐5‐hydroxytryptophan‐induced amplification of LH secretion in humans is not due to enhancement of the pituitary response to GnRH. The effect of L‐5‐hydroxytryptophan must therefore be due to its action on the hypothalamus, where it may be hypothesized that it increases GnRH release.