Serum fluctuations of total and free tryptophan levels during the menstrual cycle are related to gonadotrophins and reflect brain serotonin utilization

BACKGROUND: Serotoninergic (5-HT) neurons are suggested to regulate estrous cycle in animal models. In the present study we evaluated whether a relationship exists between the serotoninergic precursors in the central nervous system and the gonadotrophin-ovarian cyclic function. METHODS: We measured 5-HT precursors [free (FT) and total (TT) tryptophan] and LH, FSH and 17 beta-estradiol (E-2) levels in the serum of 15 fertile women with normal menstrual cycles during the follicular (cycle days 1-5, 7-11), mid-cycle (cycle days 14-16) and luteal (cycle days 17-19, 22-24) phases. RESULTS: TT and FT were significantly increased in the 7-11 and 17-19 cycle days and were decreased at mid-cycle (P < 0.01), with a cyclic and opposite behaviour when compared to that of FSH and LH. Indeed, correlation analysis through the matrix of mean values showed that LH was negatively correlated to TT (r=-0.636) and FT (r=-0.574), as well as FSH (TT, r=-0.655; FT, r=-0.663), and that TT and FT were positively correlated to each other (r=0.801; P < 0.001). Furthermore, whilst the two FT peaks reached approximately the same levels in the follicular and luteal phase, TT levels were similar to 30% higher in the luteal than in the follicular phase of the cycle: thus in the first (follicular) phase FT peak was relatively higher than that of TT, whereas the contrary occurred in the second (luteal) phase of the cycle. CONCLUSIONS: Both TT and FT levels have cyclic variations throughout the menstrual cycle, being lowest at mid-cycle (14-16 cycle days), concomitant with the highest LH and FSH concentrations, and higher before and after mid-cycle phase, coinciding with the lowest circulating LH/FSH levels. Since TT and FT levels in the plasma have cyclic changes, our study: (i) suggests that a consumption of serum serotonin precursors takes place concomitant with gonadotrophin release during menstrual cycle; (ii) may represent an in vivo model to investigate this relationship in women in different physiopathological conditions.