title: Influence of sequential doses of 5-hydroxytryptophan on prolactin release.
abstract: It is known that the administration of serotonin or its precursors induces the release of prolactin. This study was performed (1) to determine the minimal dose of 5-hydroxytryptophan that would produce a consistent and significant prolactin increase and (2) to establish the frequency of 5-hydroxytryptophan administration necessary to induce a persistent prolactin increase. Nine normal male subjects participated in 27 independent studies following pretreatment with 100 mg of carbidopa given every 8 hours for 2 days. Doses of 0.2, 0.4, and 0.8 mg/kg/hr of 5-hydroxytryptophan were initially infused for 30 minutes, and serum prolactin was measured every 15 minutes for 2 1/2 hours. The urinary 5-hydroxyindoleacetic acid/creatinine ratio was determined in aliquots collected during 3 hours before, during, and after the intravenous infusion. 5-Hydroxytryptophan at a dosage of 0.4 mg/kg/hr was the minimal amount to elicit a consistent and significant prolactin increase (p less than 0.01). A positive correlation (r = 0.907, p less than 0.002) was also demonstrated between the maximal prolactin response and the 5-hydroxyindoleacetic acid/creatinine ratio. Thus 0.4 mg/kg/hr of 5-hydroxytryptophan was administered sequentially three times at intervals of 2, 4, 6, 8, and 12 hours. With exception of the 12-hour interval a significantly smaller plasma prolactin increase was seen following the third dose of 5-hydroxytryptophan (p less than 0.05). Furthermore, the nadir for this diminished prolactin response occurred at 4 hours (p less than 0.01). This phenomenon may represent a down regulation of the serotonin receptors induced by the repetitive administration of 5-hydroxytryptophan. In conclusion, this study has demonstrated a dose-related prolactin response to increasing doses of 5-hydroxytryptophan. The maximum down regulation of prolactin release occurred when 5-hydroxytryptophan was administered at 4-hour intervals.
mesh_terms: D006916:5-Hydroxytryptophan / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D013268:Stimulation, Chemical; D013997:Time Factors
chemical_list: D011388:Prolactin; D006916:5-Hydroxytryptophan