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.

Acute effects of para-chloroamphetamine on testosterone and markers of apoptosis in seminiferous epithelium of prepubertal male rats.

Serotonin is a neurotransmitter that affects the secretion of gonadotropins and testosterone. In prepubertal male rats, serotonin has a stimulating role in testosterone secretion. Here, we used prepubertal male rats to study the effects of para-chloroamphetamine (pCA) on circulating testosterone and gonadotropins and markers of apoptosis in germ cells from day 1 to day 5 post-treatment. The intraperitoneal administration of pCA induced a significant reduction in concentrations of hypothalamic serotonin and circulating testosterone, but gonadotropins were not affected. In the seminiferous epithelium of pCA-treated rats, increased the number of germ cells positive to markers of apoptosis, concomitantly with alterations in morphometry and the presence of multinucleated germ cells. Levels of testosterone were reduced starting from 1 day after pCA was administered. The time window between the administration of the pCA and collection of samples was sufficient to detect changes in testosterone levels, in contrast with a previous work where no changes were found. There was a possible relationship between the reduction of testosterone and an increase in the number of germ cells positive to apoptosis markers. However, the mechanism that links pCA-testosterone-germ cell positive to markers of apoptosis is unknown. Our outcomes support the view that pCA exposure during the prepubertal stage has an acute impact on testosterone levels and affects the structure and physiology of seminiferous epithelium.

p-Chloroamphetamine decreases serotonin and induces apoptosis in granulosa cells and follicular atresia in prepubertal female rats.

Amphetamine derivatives negatively impact serotonin (5-HT) production, which triggers apoptosis in different tissues, depending on the receptor they bind. 5-HT in the ovary stimulates estradiol secretion, a survival factor of granulosa cells. The effect of amphetamine derivatives on the serotonergic system of the ovary and follicular development is unknown. Therefore, in this study, we investigated the effects of p-chloroamphetamine (pCA), derived from amphetamines, on estradiol production, follicular development, apoptosis of granulosa cells, and serotonin 5-HT7 receptor (R5-HT7) expression. Female rats (30 days old) were injected with 10 mg/kg of pCA intraperitoneally and were euthanized 48 or 120 h after treatment. The concentration of 5-HT in the hypothalamus decreased at 48 and 120 h after treatment and in the ovary at 120 h. The serum concentration of estradiol decreased at all times studied. Follicular atresia, TUNEL-positive (apoptotic) granulosa cells and Bax expression were elevated by pCA, but none of these effects was associated with R5-HT7 expression. These results suggest that pCA induces the dysregulation of the serotonergic system in the hypothalamus and the ovary, negatively impacting estradiol production and follicular development.