Sex Differences in Serotonergic But Not γ-Aminobutyric Acidergic (GABA) Projections to the Rat Ventromedial Nucleus of the Hypothalamus

Abstract

Hormonal conditions that elicit lordosis in female rats are ineffective in males, suggesting that this behavior is actively suppressed in males. Previous studies theorize that serotonergic and gamma-aminobutyric acidergic (GABA) inputs to the ventrolateral division of the ventromedial nucleus of the hypothalamus (VMNvl) may contribute to lordosis inhibition in males. Using triple-label immunofluorescent techniques, the present studies explored potential sex differences in the density of these projections within three hypothalamic sites: the VMNvl, the arcuate nucleus (ARC), and the dorsomedial nucleus of the hypothalamus. Antibodies directed against HuC/D, estrogen receptor (ER)-alpha and either serotonin (5-HT) or the gamma-aminobutyric acid synthetic enzyme glutamic acid decarboxylase-65 were used to compare the densities of glutamic acid decarboxylase (GAD)-65- and 5-HT-containing fibers in each brain area, the percentage of VMNvl HuC/D immunoreactive (ir) neurons that contained ERalpha, and the percentage of HuC/D and ERalpha double-labeled cells receiving apparent contacts from 5-HT fibers between adult, gonadectomized male and female rats. The densities of VMNvl and ARC 5-HT immunolabeled fibers were significantly higher in the males, and the percentage of VMNvl HuC/D-ir neurons containing ERalpha was significantly higher in the females. The percentage of HuC/D-ir cells contacted by 5-HT fibers was significantly higher in the males, compared with the females, but there was no sex difference in the proportion of those cells receiving contacts that were ERalpha-ir. Neonatal administration of estradiol but not genistein masculinized 5-HT content in the adult female VMNvl, but the percentage of HuC/D-ir cells colabeled with ERalpha was not significantly affected by treatment. A similar, but not statistically significant, pattern was observed in the ARC. These findings suggest that the development of serotonergic inputs to the male VMNvl is orchestrated by neonatal estradiol exposure. The hormone-dependent organization of these 5-HT projection patterns may be an important developmental mechanism accounting for sex-specific behaviors in adulthood.

Embryonic and postnatal development in experimental tryptophan deprived rats. A preliminary study

“…Besides these findings in our study we observed both in male and female rats of experiments 1 and 2, dramatic low plasma levels of PRL, confirming so once again that a close relationship exists between 5-HT and this pituitary hormone (Carlsson et al 1987;Patisaul et al 2008). Such finding, however, does not be considered surprising since it seem clear that 5-HT directly acts on the anterior pituitary cells by specific serotonergic nervous pathways.…”

Inhibitory role of the serotonergic system on estrogen receptor α expression in the female rat hypothalamus

“…Similar results have been demonstrated in female rats with DR lesions [10]. The VMN contains large numbers of serotonergic fibers and the distribution pattern is sexually dimorphic [18]. The VMN receives ipsilateral 5-HT inputs from the DR and bilateral 5-HT inputs from the MR and the number of inputs was found to be comparable between these raphe nuclei [12].…”

Modulation of monoamine neurotransmitters in fighting fish Betta splendens exposed to waterborne phytoestrogens

“…A study on rats showed that genistein treatment does not affect serotonin content of the ventromedial nucleus of the hypothalamus (Patisaul et al 2008), but genistein and other phytoestrogens are known to affect serotonin re-uptake (Ofir et al 2003). Furthermore, mammalian 5-HT neurons are ER b -rich (Bethea et al 2002), suggesting that genistein should be capable of significant modulation of serotonergic activity (Whitten Patisaul et al 2002).…”