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

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.

Dorsal and medial raphe nuclei participate differentially in reproductive functions of the male rat.

BACKGROUND: Innervation of the hypothalamus and median eminence arise from the dorsal and medial raphe nuclei (DRN and MRN, respectively). The hypothalamus regulates the secretion of gonadotropins, which in turn regulate the reproductive function of males and females. However, it is not known the role of raphe nuclei in male reproductive function. Our goal was to investigate the role of the DRN and MRN in the regulation of the testicular function and secretion of gonadotropins in prepubertal rats. METHODS: Dihydroxytryptamine (5,6-DHT) in ascorbic acid was used to chemically lesion the DRN or MRN. Rats were treated at 30 days-of-age and sacrificed at 45 or 65 days-of-age. Sham-treated controls were injected with ascorbic acid only. Negative controls were untreated rats. The damage induced by the 5,6-DHT was monitored in coronal serial sections of DRN and MRN; only the animals in which lesion of the DRN or MRN was detected were included in this study. As output parameters, we measured the concentrations of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the anterior (AH) and medial (MH) hypothalamus by high performance liquid chromatography (HPLC); whereas, circulating concentrations of gonadotropins and sexual steroids were measured by radioimmunoassay. Seminiferous epithelium and sperm quality were also evaluated. RESULTS: Lesion of DRN or MRN does not induced changes in concentrations of LH, progesterone, and testosterone. Compared with the control group, the sham or lesion of the DRN or MRN did not modify noradrenaline or dopamine concentrations in the AH and MH at 45 or 65 days of age. Meanwhile, serotonin concentrations decreased significantly in lesioned rats. Lesion of DRN induced significantly lower concentrations of FSH regardless of age; similar lesion in the MRN had no impact on FSH levels. Sperm concentration and motility were significantly decreased in the same animals. The lesion of the MRN does not induced changes in the seminiferous epithelium or gonadotropin levels. Our results suggest that raphe nuclei regulate differentially the male reproductive functions. CONCLUSIONS: The DRN but not the MRN regulates the secretion of gonadotropins and testicular function.

Comparative effects of injecting 5,6-dihydroxytryptamine in the dorsal or medial raphe nuclei on rat puberty.

The role played by the serotoninergic system in the control of puberty onset and first ovulation in rats is studied in this paper by analyzing the effects of injecting the neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) into the dorsal (DRN) or medial (MRN) raphe nucleus of 30-day-old female rats. Complete lesion to the DRN resulted in the blockade of ovulation and a decrease in both the number of ovarian follicles and the serum concentration of follicle stimulating hormone (FSH). This treatment was also found to be associated with an increase in serotoninergic activity in the anterior and medial hypothalami. A lesion to the central portion of the DRN resulted in a significant decrease in the concentration of progesterone in serum and in the number of ova shed by ovulating animals. The lesion to the lateral portion of the DRN did not have an apparent effect on ovulation rate, the number of ova shed, nor in hormone serum concentration. The injection of propranolol to rats with a lesion to the DRN restored ovulation in 73% of treated animals and returned serotoninergic activity in the anterior hypothalamus to levels similar to those of sham-operated animals. In turn, in the medial hypothalamus, the increase in serotoninergic activity was not modified. The results presented herein suggest that serotoninergic inputs to the anterior hypothalamus have a direct influence on gonadotropin secretion and first ovulation, while the noradrenergic innervation exerts an indirect influence.