Endocrine mechanisms for the formation of sex-related differences in hepatic estrogen receptor content and their significance for the realization of an estrogen effect on angiotensinogen blood level in rats.

The use of a modified, adequate method of quantification of estrogen receptors has permitted us to prove the existence of sex-specific peculiarities in rat liver estrogen reception and their significance for the realization of sex-dependent changes in angiotensinogen plasma level after estrogenization. Endocrine mechanisms for the formation of sex-related differences in hepatic estrogen receptor content in rats were investigated in detail. The investigation shows that androgens have negative regulatory influence on the hepatic estrogen receptor level in rats. Estrogens and adrenal and thyroid hormones do not take part in the regulation of hepatic estrogen receptor content in rats. It has been proven that the decisive role in keeping up a certain estrogen receptor concentration in hepatocytes belongs to pituitary growth hormone. It was shown for the first time that androgens are able to inhibit the stimulatory effect of growth hormone on hepatic estrogen receptors.

[Role of hormones in maintaining the sex-differentiated level of estrogen receptors in rat liver cytosol]. / Rol' nekotorykh gormonov v podderzhanii poldifferentsirovannogo urovnia retseptorov éstrogenov v tsitozole pecheni krys.

A study was made of the endocrine mechanisms of the formation and maintenance of a sex-differentiated level of estrogen receptors (ER) in rat liver cytosol. The administration of testosterone-propionate (TP) at a dose of 3 mg for 3 days was shown to cause a significant decrease in the concentration of ER in the liver of gonadectomized animals to the level in intact male rats. In a week after the discontinuation of TP, a complete restoration of the basal level of receptors was observed. Neonatal and prepubertal administration of TP to gonadectomized male rats at early stages of ontogenesis made no effect on the level of ER in the liver cytosol of these animals at the age of 12-14 weeks. The removal of the adrenal and thyroid glands produced no changes in the level of ER in the liver of rats of both sexes. Hypophysectomy in rats resulted even on the 1st day in a decrease in ER concentration in the liver of male and female animals to the same basal level which later on remained unchanged. Ectopic transplantation of a homologous hypophysis and human STH administration led to a significant rise of the level of ER in hypophysectomized animals. TP inhibited a stimulating effect of STH in rats with the removed hypophysis.

[Sex differences in the accumulation of estrogen receptors in nuclei of liver cells and increase of angiotensinogen concentration in the blood of rats after administration of low doses of synthetic estrogens]. / Polovye razlichiia v nakoplenii éstrogennykh retseptorov v iadrakh kletok pecheni i uvelichenii kontsentratsii angiotenzinogena v plazme krovi krys pri vvedenii niznikh doz sinteticheskikh éstrogenov.

The significance of sex differences in the level of estrogen receptors (ER) in hepatocytes for direct effects of estrogens in male and female rat livers was investigated. 4-5-fold increase in ER level and 20-30%-elevation in plasma angiotensinogen (AG) occurred after a single injection of 0.5 microgram of hexestrol (HE) in female and gonadectomized male rats. In male liver, where the cytosol ER content is two fold lower than that in female rats, nuclear ER level was shown to be very low and unchanged after HE injection, plasma AG also did not change. Injection of 0.5 microgram of ethinylestradiol produced similar effect. Injection of a greater dose of estrogen caused an enhancement in plasma AG level in males. The existence of sex differences in hepatic ER level seems to cause in some conditions different response of metabolic processes in male and female rat liver after estrogenization.

[The effect of the administration of different estrogens on the content of estrogen receptors in the cytosol and nuclear subfractions of liver cells and on the level of angiotensinogen in the blood plasma of rats]. / Vliianie vvedeniia razlichnykh éstrogenov na soderzhanie éstrogennykh retseptorov v tsitozol'noi i iadernoi subfraktsiiakh kletok pecheni i uroven' angiotenzinogena v plazme krovi krys.

The level of estrogen receptors (ER) in the cytosol and nuclear subfractions of female rat hepatocytes was studied 1 h and plasma angiotensinogen (AG) concentration 24 h after single and multiple administration of different doses of estradiol (E2) and synthetic estrogens. Synthetic weakly metabolized estrogens, used at doses corresponding to physiological concentrations of the natural female sex steroid, were shown to be much more effective than E2 in relation to ER redistribution between the cytosol and nuclear fractions of hepatocytes as well as in relation to the stimulation of AG production by the liver. Differences in the ER level in hepatocytic nuclei 1 h after single or multiple administration of the same estrogen were undetectable. An increase in a plasma AG level after a single injection of estrogens was noted after achieving a certain threshold (more than 3-fold as compared to the normal level) level of ER accumulation in hepatocytic nuclei. The sensitivity of AG production by the liver to a stimulating effect of low doses of estrogens was on the increase as a result of their repeated effect in prolonged administration and combined administration of E2 and glucocorticoids.

[Sex differences in the level of cytosol estrogen receptors in the rat liver]. / Polovye razlichiia v soderzhanii tsitozol'nykh retseptorov éstrogenov v pecheni krys.

The procedure designed for the estimation of estrogen receptors (ER) in rat liver cytosol using sodium thiocyanate was shown to be useful for differential quantification of the ER level in liver cytosol of male rats, containing the unusual estrogen-binding protein. The ER concentration in rat liver cytosol was shown to be a sex dependent feature: its content in male rats (55 +/- 4 fmol/mg of protein) was lower (p 0.001) than that in female rats (116 +/- 4 fmol/mg of protein). The differences in the ER content were revealed only after maturation and disappeared after hypophysectomy of adult rats. Gonadectomy of males performed on the 1st postnatal day or in the pre- or postpubertal period resulted in complete "feminization" of the ER content in these animals. Ovariectomy in female rats at all stages of ontogenesis did not influence the ER level in liver cytosol. It was concluded that androgens have no programming, but only a negative regulatory influence on the ER level in rats.

[Use of variants of the ligand metabolism method for determining the estrogen receptor content in subfractions of liver cells after the administration of various doses of estradiol]. / Primenenie variantov metoda ligandnogo obmena dlia opredeleniia soderzhaniia éstrogennykh retseptorov v subfraktsiiakh kletok pecheni pri vvedenii razlichnykh doz éstradiola.

The regularities of the time course and intracellular distribution of estrogen receptors (ER) of the liver of ovariectomized female rats after a single injection of 1, 25 and 500 micrograms of E2 were investigated using new variants of a method of ligand exchange. The ER content in liver cells was 12275 +/- 1100 (n = 33) bonds per cell (by one order lower than in the uterus). A single injection of E2 at a dose of 1 micrograms caused no changes in the ER content in the liver cytosol and nuclear fractions whereas reciprocal redistribution of ER between the cytosol and nuclei was noted in the uterus. A single injection of 25 and 500 micrograms of E2 to ovariectomized female rats resulted in dose dependent ER redistribution between the cytosol and nuclear fractions, the development of "deficiency" of the total ER content in liver cells was also dose dependent. The main regularities of the time course and intracellular distribution of ER in the liver of ovariectomized female rats after a single injection of large doses of E2 were similar to those in common target organs for estrogens.

[Determination of free and bound forms of estrogen receptors in rat liver cytosol using a method of ligand turnover at low temperature]. / Opredelenie svobodnykh i sviazannykh form retseptorov éstrogenov v tsitozole pecheni krys metodom ligandnogo obmena pri nizkoi temperature.

A procedure is described for estimation of free and bound estrogen receptors in rat liver cytosol at low temperature using ligand turnover in presence of sodium thiocyanate. Total content of estrogen receptors was similar in cytosol of intact and ovariectomized rat females but about 30% of estrogen receptors were estimated in cytosol of intact animals as estrogen-receptor complexes. Within 24 hrs after single administration of 500 mg estradiol E2 into ovariectomized rat females approximately 50% of estrogen receptors were shown to be bound with hormone in cytosol.

[Features of the functioning of the catecholamine and adrenocortical systems of patients with depression and different degrees of emotional tension]. / Osobennosti funktsionirovaniia katekholaminovoi i adrenokortikal'noi sistem u bol'nykh depressiei s razlichnoi sistem u bol'nykh depressiei s razlichnoi vyrazhennost'iu émotsional'nogo napriazheniia.

The catecholamine and adrenocortical systems in 52 patients with depression were studied with regard to the degree of their emotional tension. On the basis of the clinical characteristics of the depressive syndrome the patients were divided into two groups: the stressory hyperergic type (Group 1) and the torpid hypoergic type (Group 2). Some characteristics of the studied systems proved common for both groups: they increased secretion of 11-hydroxycorticosteroids and impairment of the mechanisms of negative feedback in the regulation of adrenocortical activity, as well as a decrease in the excretion of dopamine, adrenaline, and DOPA in the presence of a relative acceleration of catecholamine inactivation. Along with the characteristics common for all the patients studied, the authors revealed a highly significant difference in noradrenaline excretion between Groups 1 and 2: it was normal in Group 1 and decreased three-fold in Group 2. The findings obtained are discussed in the light of the catecholamine hypothesis of depression development.

[Diagnostic informative value of the method of competitive transcortin binding for determining corticosteroid levels in hypercorticism]. / Diagnosticheskaia informativnost' metoda konkurentnogo sviazyvaniia transkortinom dlia opredeleniia kortikosteroidov pri giperkortitsizme.

The level of nonmetabolized forms of the corticosteroids hydrocortisone and corticosterone in the blood and urine were determined in 3 groups of patients: with the Icenko-Cushing disease and syndrome and neuroendocrine form of the hypothalamic syndrome. The determination of the level of these hormones, a study of their circadian rhythm by the method of concurrent protein binding have shown that these indices are rather informative and can be recommended as diagnostic and differential criteria for the evaluation of the hypothalamo-hypophyseal-adrenal system.