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.

The role of sex steroids in the formation of sex-differentiated concentrations of corticosteroid-binding globulin in rats.

The role of sex steroids in the programming of the level of serum corticosteroid-binding globulin (CBG) in the rat has been studied at different stages of ontogenesis. The CBG content in the serum of mature female rats was 2.5 times higher than that in male rats. Sexual dimorphism of CBG content was absent in immature animals of 3-4 weeks of age. Castration of mature rats led to a 40-50% increase in CBG content. The CBG concentration in mature females or castrated adult males treated with testosterone propionate (TP; 3 mg/day for 4 days) was decreased by 40-50% compared with vehicle-treated rats. Oestradiol injection (1 microgram/day for 4 days) had no influence on CBG levels in mature male and ovariectomized adult female rats. Immature rats were castrated on days 1, 7, 14, 21, 28 or 35 of age and the CBG level was determined at 10-12 weeks of age. The CBG content of rats castrated up to day 28 of age was 2.5 times higher than that in mature males and did not differ from that in mature females. The CBG content of male rats castrated on day 35 of age was the same as that of adult castrated males. The CBG level in castrated rats treated with TP (1.25 mg for days 1-3 or 300 micrograms/day for 5 days after castration at day 7 up to day 26) did not differ from that in controls (i.e. vehicle-treated rats).(ABSTRACT TRUNCATED AT 250 WORDS)

[Role of the pituitary gland in the sex differentiation of the level of corticosteroid-binding globulin in rats]. / Rol' gipofiza v polovoi differentsirovke urovnia kortikosteroid- sviazyvaiushchego globulina u krys.

A study was made of the role of hypophyseal hormones in the regulation of the sex-associated level of corticosteroid-binding globulin (CBG) in the serum of female and male rats. Pituitary body removal did not change the level of CBG in males but caused its decrease in females to the level in intact males. Ectopic transplantation of the homologous pituitary body under the renal capsule increased the level of CBG in animals of both sexes. Intermittent infusion of STH did not change CBG content in hypophysectomized female rats and lowered it in intact females. A negative effect of androgens on the studied sign did not manifest itself either against a background of hypophysectomy or hypophyseal ectopy. Corticosteroids and thyroid hormones preserved their effects with regard to the level of CBG in hypophysectomized rats.

[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.

[The characteristics of the programming action of androgens on the formation of sexual dimorphism in the level of corticosteroid-binding globulin in rats]. / Osobennosti programmiruiushchego deistviia androgenov na formirovanie polovogo dimorfizma urovnia kortikosteroidsviazyvaiushchego globulina u krys.

The role of sex steroids in the programming of the level of serum corticosteroid binding globulin (CBG) of male and female rats has been studied at different stages of ontogenesis. It was shown that castration of adult males lead to the increase of the level of CBG, but not to the elimination of sex differences. Gonadectomy of males up to 28th day of postnatal life results in complete feminization of the CBG content in these animals at the age of 10-12 weeks. The castration after 35th day of life does not prevent the formation of the male phenotype of CBG content. The results of administration of testosterone-propionate (TP) to castrated males at different periods of ontogenesis suggests that the sensitivity to irreversible negative action of androgens appears after 28th day of life and disappears after the puberty. It was concluded that short period of ontogenesis from 29th to 35th days of life is critical for the realization of the irreversible masculinization of CBG level upon the influence of androgens in the physiological conditions. It was found that injections of both synthetic estrogens diethylstilbestrol or TP in the sensitive period of ontogenesis lead to the expression of male phenotype of CBG level in a similar fashion.

[Clinical characteristics of disorders of sexual functions in patients with rheumatoid arthritis]. / Klinicheskaia kharakteristika narushenii seksual'noi funktsii u bol'nykh revmatoidnym artritom.

The method of structural analysis was used to study the presence of sexual disorders in 26 male patients with rheumatoid arthritis (RA). The incidence of sexual disorders was 42.3 per cent (11 patients). In this case the ejaculatory and neurohumoral components of the copulative cycle were mostly disturbed. Sexual dysfunction developed during the disease and was often associated with exacerbation of RA. Disorders in pubertal development were revealed in none of the patients. But patients with a disturbed sexual function exhibited a significant decrease in the total cumulative index in the male sexual formula, in the level of total and free testosterone, a rise in the content of prolactin. Possible causes and mechanisms of sexual disorders in male patients with RA are discussed.

[Role of corticosteroids in the regulation of the sex-differentiated level of corticosteroid-binding globulin in rats]. / Rol' kortikosteroidov v reguliatsii differentsirovannogo po polu urovnia kortikosteroidsviazyvaiushchego globulina u krys.

A study was made of the role of the adrenal cortex in the formation and modulation of the level of corticosteroid-binding globulin (CBG) in the serum of male and female rats. Corticosteroids were shown to be potent negative regulators of a CBG level in rats, the level of this protein being more sensitive to the action of these hormones in male rats than in females. Adrenalectomy in mature as well as in prepubertal rats did not level down sex differences in the level of CBG. A study of possible interdependent influence of corticosteroids and sex hormones on the level of CBG has shown that adrenocortical hormones produce an independent direct effect of the level of CBG. Producing a negative effect on the level of CBG, corticosteroids are involved in the modulation of sex dimorphism of the level of this protein in rats, enhancing sex differentiation of the CBG level in males and weakening it in female rats.

[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.

[Mediate mechanism of positive effect of estrogens on the level of corticosteroid-binding globulin in rats]. / Oposredovannyi mekhanizm pozitivnogo deistviia éstrogenov na uroven' kortikosteroidsviazyvaiushchego globulina u krys.

The mechanism of estrogen action on CBG level in blood serum was studied in the experiments on white rats. It was shown that estradiol injection at the dose 100 micrograms for 3 weeks induced the increasing of CBG serum level in intact males, but it was not changed in the gonadectomized males and females. The presence of the positive effect of exogenic estrogens only in the intact males was connected with the estrogen depression of testis function. It suggests the absence of direct positive estrogens action on the level of CBG in the rats. The estrogen effect is not mediated by adrenal corticosteroids, and has independent negative action on CBG level in the rat. Thus, estrogen does not participate in the endocrine regulation of CBG content in the mature rats.

[Mechanisms of sex differentiation of the level of corticosteroid-binding globulin in rats]. / Nekotorye aspekty mekhanizmov polovoi differentsirovki urovnia kortikosteroidsviazyvaiushchego globulina u krys.

The role of sex steroids was studied at different stages of ontogenesis in the regulation and programming of the level of corticosteroid binding globulin (CBG) in the blood serum of female and male rats. The blood concentration of CBG was shown to be a sex determined feature: its level in female rats was a 2.5-fold higher than that in male rats; sex differences of this function of the liver were preserved in a primary culture of hepatocytes. Androgens (A) in adult animals were shown to decrease the level of CBG, and estrogens (E) did not influence the blood level of this protein. Castration of adult males leading to an increase of the level of CBG by 1.5-fold did not eliminate sex differences. However gonadectomy of males on the first day of the life or in prepubertal period (at the age of 3-4 weeks) resulted in complete "feminization" of the CBG content in these animals at the age of 10-12 weeks. Ovariectomy in female rats in the prepubertal period did not influence the level of CBG in adult female rats. The administration of A to females or castrated males did not prevent the development of a high level of CBG at older age. Irreversible suppression of the level of CBG in adult animals could be artificially induced by the administration of A to gonadectomized female and male rats in the prepubertal period.(ABSTRACT TRUNCATED AT 250 WORDS)

[Function of the reproductive system in pre- and pubescent girls with diffuse toxic goiter and hypothyroidism]. / Sostoianie reproduktivnoi sistemy u devochek pre- i pubertatnogo vozrasta s diffuznym toksicheskim zobom i gipotireozom.

Altogether 70 girls of pubertal age were examined: 50 with diffuse toxic goiter and 20 with hypothyrosis. A clinical picture of "hypoestrogenism" and menstrual disturbance confirmed by the results of clinical and gynecological examination and ultrasonic investigation was noted in the patients. A significant rise of the level of gonadotropic hormones correlating with the severity of disease, and a rise of the level of testosterone-estradiol binding protein were revealed. The results of the investigation suggest that changes in the reproductive system resulting from thyroid dysfunction age determined by disturbance of different links of hormonal regulation of the hypothalamo-hypophyseal-gonadal system.

[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.

[Effect of estradiol and other endocrine factors on the level and dynamics of estrogen receptors in the liver cells of rats]. / Vliianie éstradiola i drugikh éndokrinnykh faktorov na uroven' i dinamiku éstrogennykh retseptorov v kletkakh pecheni krys.

The authors studied the effects of different doses of estradiol (E2) on the level of estrogen receptors (ER) in female rat hepatocytes and the dynamics of ER distribution between the cytosol and nuclear cell fractions and compared the changes in the ER level in the liver in different endocrine states of the body. It was shown that the ER level in hepatocytes was far lower than in uterine cells and drastically increased during puberation and after ovariectomy. It was also found that the ER level in hepatocytes was dependent on pituitary functions. After a single injection of E2, the ER level in cytosol descended and that in the nucleus rose. The degree of ER reduction in cytosol and increase in the nucleus correlated with the dose of E2. The dynamics of intercombined changes in the levels of cytosol and nuclear ER was studied at different time intervals following the injection of different doses of the hormone. Some essential organ-specific features of E2 reception in the liver were revealed. Different mechanisms of the control of ER content in the liver and uterus are postulated.

[Comparative analysis of estrogen receptor level in the liver and angiotensinogen level in the blood plasma of rats after administration of estradiol in association with other endocrine factors]. / Sravnitel'nyi analiz dinamiki urovnia estrogennykh retseptorov v pecheni i angiotenzinogena v plazme krovi krys pod vliianiem vvedeniia éstradiola v sochetanii s vozdeistviem riada drugikh endokrinnykh faktorov.

A study was made of the level of hepatocyte estrogen receptors (ER) and of angiotensinogen [AG) in the blood plasma of rats after the administration of different doses of estradiol (E2) in combination with the exposure to some other endocrine factors. A single administration of E2 has been shown to cause two types of effects depending of the dose of a hormone administered and the time following injection: an increase in the AG level in the plasma and interrelated changes of the ER content in the cytosol and hepatocyte nuclei. These effects were most noticeable after the administration of 500 micrograms of E2. In this case the ER content decreased significantly in the cytosol and increased in the cell nucleus. An elevated ER level in the nucleus was preserved for 6-24 h and at this period AG production in the hepatocytes occurred and gradually increased within 24 h. An increase in AG production and the level and time of ER delay in the nuclei (r = +0.75, P less than 0.01) showed a high direct correlation. The expression of the effect of E2 high doses inducing AG synthesis depended on the body endocrine status which in its turn determined a certain level of E2 reception in hepatocytes. A low level of ER in the hepatocytes of hypophysectomized or immature rats corresponded to the absence or suppression of the E2 effect on AG production in the liver. An increase in the ER concentration in the cell as a result of the growth hormone administration to hypophysectomized or mature female rats was accompanied by the appearance or a rise of the sensitivity to the E2 effect.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of estradiol and a series of other endocrine factors on the angiotensinogen level in rat blood plasma]. / Vliianie éstradiola i riada drugikh éndokrinnykh faktorov na uroven'angiotenzinogena v plazme krovi krys.

The effects of estradiol (E2) and some other endocrine factors on rat plasma angiotensinogen (AG) have been studied. AG was determined by RIA. Both single and multiple injections of E2 to female rats were shown to cause a dose-dependent increase in AG in the blood. The effect of E2 was inhibited by cycloheximide. Multiple injections of E2 to male rats caused the same hepatic AG synthesis induction as those to female rats. Unlike E2, long-term treatment with large doses of testosterone propionate did not affect AG synthesis. AG levels in blood plasma of ovariectomized and immature female rats did not differ from those seen in mature intact rats. However, immature females were insensitive to the stimulant effect of the pharmacological doses of E2. Drastic reduction in hepatocyte sensitivity of the stimulant effect of E2 was seen in hypophysectomized female rats as well. Treatment of hypophysectomized animals with human GH, which did not affect AG levels per se, caused an almost complete recovery of hepatocyte ability to react by increasing AG synthesis in response to E2 injection. The possible role of different hormonal and genetic hepatotrophic factors in hepatocyte reactivity to the stimulant effect of E2 on AG synthesis is discussed.

[Phylogenesis of steroid-transport proteins in the blood: detection and characteristics of the sex-steroid-binding protein in the blood plasma of the carp]. / O filogeneze belkov transporta steroidov v krovi: vyiavlenie i osobennosti sekssteroidsviazyvaiushchego belka plazmy krovi karpa.

The interaction of 3H-5 alpha-dihydrotestosterone, 3H-progesterone, 3H-cortisol and 3H-testosterone with the Cyprinus carpio blood proteins was studied by means of adsorption on the activated charcoal and equilibrium dialysis. Protein which specifically binds androgen-, estradiol-, progesterone- and, to a lesser degree, corticosteroids was present in the blood plasma. The equilibrium constants of 3H-steroid association with this protein, the concentration off steroid-binding sites and its hormonal specificity of the affinity were determined. There were no pronounced sex dimorphism and marked alterations in the concentration of protein-binding sites during ontogeny and reproduction process. Protein, being specialized on the corticosteroid transport, was not revealed in the Cyprinus carpio blood plasma. It is suggested that the formation of differentiated corticosteroid-binding globulin and sex steroid-binding protein, typical of higher vertebrates, occurred during the stage of teleostei.