The differential sensitivity of the hypothalamic-hypophysial-ovarian axis to 5-hydroxytryptophan alters the secretion of estradiol

Exp Physiol. 2024 Mar;109(3):365-379. doi: 10.1113/EP091158. Epub 2023 Dec 8.

Abstract

Serotonin [5-hydroxytryptamine (5-HT)] modulates ovarian function. The precursor of 5-HT, 5-hydroxytryptophan (5-HTP), has been used to treat depression. However, the effects of 5-HTP on ovarian and reproductive physiology remain unknown. In this research, we analysed the impact of 5-HTP on the monoaminergic system and its interactions with the reproductive axis and ovarian estradiol secretion when administered by distinct routes. Female rats 30 days of age were injected with 5-HTP i.p. (100 mg/kg), into the ovarian bursa (1.5 µg/40 µL) or into the median raphe nucleus (20 µg/2.5 µL) and were killed 60 or 120 min after injection. As controls, we used rats of the same age injected with vehicle (0.9% NaCl). Monoamine, gonadotrophin and steroid ovarian hormone concentrations were measured. The injection of 5-HTP either i.p. or directly into the ovarian bursa increased the concentrations of 5-HT and the metabolite 5-hydroxyindole-3-acetic acid in the ovary. For both routes of administration, the serum concentration of estradiol increased. After i.p. injection of 5-HTP, the concentrations of luteinizing hormone were decreased and follicle-stimulating hormone increased after 120 min. Micro-injection of 5-HTP into the median raphe nucleus increased the concentrations of 5-HT in the anterior hypothalamus and dopamine in the medial hypothalamus after 120 min. Our results suggest that the administration of 5-HTP either i.p. or directly into the ovarian bursa enhances ovarian estradiol secretion.

Keywords: 5-hydroxytryptophan; estradiol; gonadotrophins; hypophysis; hypothalamus; ovary; serotonin.

MeSH terms

  • 5-Hydroxytryptophan* / metabolism
  • 5-Hydroxytryptophan* / pharmacology
  • Animals
  • Estradiol / metabolism
  • Estradiol / pharmacology
  • Female
  • Hypothalamus / metabolism
  • Ovary / metabolism
  • Rats
  • Serotonin* / metabolism

Substances

  • 5-Hydroxytryptophan
  • Serotonin
  • Estradiol