Hypothalamo-pituitary control of the cell-mediated immunity in rat embryos: role of LHRH in regulation of lymphocyte proliferation.

The role of the neuroendocrine system in the development of cell-mediated immunity has been studied in fetal rats. The spontaneous and mitogen-induced proliferation of liver lymphocytes and thymocytes was evaluated in vitro in rats at the 22nd prenatal day following surgical ablation of the forebrain (encephalectomy) or of the entire brain and pituitary (decapitation) in rat fetuses in utero at the 18th day. Non-operated and sham-operated fetuses served as controls. The ablation of the entire brain and pituitary in rat fetuses resulted in an increase (40-60%) of spontaneous proliferation of liver and thymic cells in comparison with sham-operated fetuses. The ablation of the forebrain including the hypothalamus caused a decrease in the mitogenic proliferative response of thymocytes and liver lymphocytes for 40 and 20%, respectively. The ablation of the entire brain including the hypothalamus and pituitary resulted in a 80% decrease of the proliferative response of thymocytes and in the full suppression of proliferation of liver lymphocytes. The immune proliferative response was restored by the LHRH administration either systemically to operated fetuses (0.2 microg/fetus) or to the cell culture (10(-9) and 10(-7) M). It was concluded that the central nervous system was important for maturation of the immune system in rats during the prenatal period. In particular, neuroendocrine system are likely to play a major role as LHRH treatment in vitro and in vivo appeared to contribute to this regulation.

Prolactin secretion and its dopamine inhibitory control in rat fetuses.

This study has determined in rats the ontogenetic schedule of the onset of pituitary prolactin (PRL) synthesis and release as well as of the establishment of the dopamine (DA) inhibitory control of PRL secretion. RIA recognized PRL traces in the pituitary at the 18th embryonic day (E18), although a clearly detectable amount of this hormone was first measured at E20, suggesting the onset of PRL synthesis. The PRL level in the pituitary increased significantly by E22, in females to a higher extent than in males. Decapitation of fetuses did not cause any change in the PRL plasma level in males showing no PRL release from the pituitary until term. Conversely, there was a slight but significant fall of plasma PRL in decapitated females, suggesting PRL release from the pituitary. An inhibition of DA receptors on lactotropes of fetuses resulted in an increased level of plasma PRL at E20, but not at E18, while the pituitary content of PRL remained unchanged. The same treatment at E22 caused a significant increase of the PRL concentration in plasma and a concomitant fall in the pituitary that could be prevented by preliminary encephalectomy. These data show that the tuberoinfundibular DA system begins to inhibit PRL release from lactotropes between E20 and E22, completely arresting PRL release from the pituitary in males but not in females.

Androgen-dependent sex differences in the hypothalamic serotoninergic system.

This study has attempted to fulfill our knowledge on the sex differences in the hypothalamic serotoninergic (5-HT) system in adult rats, and also to evaluate the role of neonatal androgens in the appearance of this sexual dimorphism. Such integrative characteristics of the 5-HT system as 5-HT content and specific uptake were estimated and compared in the anterior and middle hypothalami in intact adult females and males, as well as in neonatally castrated adult males. According to our data, the 5-HT content and [3H]5-HT specific uptake both in the anterior and middle hypothalami of intact females exceeded significantly those in intact males. Neonatal castration of males resulted in an increase of the 5-HT content and [3H]5-HT uptake in both hypothalamic regions up to their levels in intact females. Thus, the present study provides new information on the sex differences in the hypothalamic 5-HT system, which are apparently related to the neonatal masculinization of the hypothalamus.

Ontogenesis of the hypothalamic catecholaminergic system in rats: synthesis, uptake and release of catecholamines.

The development of the hypothalamic catecholaminergic system during ontogenesis in rats has been studied with glyoxylic acid histofluorescent method in vivo and with isotopic biochemical technique in vitro. It has been demonstrated that at the 15th fetal day the catecholaminergic system was functionally inactive at least in its ability for the uptake and K(+)-stimulated release of catecholamines. Since the 16th fetal day, hypothalamic neuronal elements gained an ability for synthesis of catecholamines, their specific uptake and K(+)-evoked release. Over the subsequent two days, the intensity of the fluorescent intraneuronal product rose considerably showing the increase of either synthesis or accumulation of catecholamines. Simultaneously, the values of the uptake and K(+)-stimulated release of the exogenous radioactively-labelled dopamine increased significantly. The intensity of the fluorescence of the hypothalamic neuronal elements dropped from 20th fetal until the ninth postnatal day, whereas the specific uptake doubled over the same period reaching its adult level. By the 21st postnatal day the reaccumulation of the fluorescent product occurred.