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V B Rozen

Publications and source records attributed to V B Rozen.

At least 19 recordsLinked to original sources
PubMed1993

Inheritance of androgen program of male-specific expression of unusual estrogen-binding protein by daughter hepatocytes at rat liver regeneration.

A possibility of inheritance of androgen and basic genetic programs at the level of unusual estrogen-binding protein (UEBP) by daughter hepatocytes was investigated. Liver regeneration after partial (2/3) hepatectomy or after selective poisoning of hepatocytes of the central zone of hepatic lobules with CCl4 in adult rats were used as models of total and zonal proliferation of hepatocytes, respectively. UEBP content and the pattern of its tissue expression in the course of liver regeneration were monitored by radioligand and immunocytochemical technique. In animals of all groups possessing the androgen program of UEBP expression (intact, castrated and/or hypophysectomized males, and ovariectomized females treated with androgen) UEBP content was shown to be similarly high before initiation and after completion of liver regeneration. Unlike in males, in androgenized females a transient 4-fold increase of UEBP concentration on day 4 after partial hepatectomy was observed. In animals with a basic genetic program at the level of this protein (ovariectomized females, neonatally castrated males) only trace amounts of UEBP were observed in intact as well as in regenerated liver. The data were confirmed by immunocytochemical technique. A gradient mode of distribution of UEBP-contained cells within hepatic lobules with the highest specific staining around central veins was found by immunocytochemical technique in males. Specific staining of centrolobular and periportal hepatocytes was 7- to 10-fold in intact, and 4- to 6-fold in castrated and/or hypophysectomized males. In intact females specific staining was distributed uniformly at extremely low levels similar to that in periportal hepatocytes of males. Androgen administration to ovariectomized females stimulated a significant and stable increase of UEBP content in two layers of hepatocytes surrounding the central vein. Profiles of specific staining of hepatocytes within the hepatic lobules similar to that in control animals were observed after the completion of liver regeneration of different groups of rats. The results obtained suggest all the hepatocytes to be targets for androgen programming, natural in males or experimental in females, while the extent of expression of this program depends on the position of a hepatocyte within the liver lobules and the sex of the animal.

Androgens↗
PubMed1992

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.

Angiotensinogen↗
PubMed1992

Evidence for direct action of testosterone on rat liver cells: in vivo and in vitro induction of unusual estrogen-binding protein.

We demonstrate that on the rat liver, testosterone (T) induced differentiated functions and enhanced unusual estrogen-binding protein (UEBP) content through mechanisms dependent on cell activation by androgens, the presence of growth hormone (GH) and the hormonal status of the animal. To determine whether liver cells are a target for androgens, we measured T effects on UEBP in gonadectomized adult male and female rats in vivo and in vitro. In ovariectomized rats, T increased 8- to 9-fold UEBP levels that remained constant during 10 days. Also in vitro, using hepatocytes from ovariectomized rats, T alone increased UEBP levels 3-fold in a dose-response pattern. Combining a fixed low dose of GH with different concentrations of T increased UEBP 2-fold above T alone. Whereas GH alone had no effects in ovariectomized rats, hepatocytes were responsive to GH, in a dose dependent pattern that was abolished when T was used together with GH. On the other hand, T alone had no effect in hypophysectomized-ovariectomized animals. The latter group was rendered T responsive after the simultaneous injection of GH with T that increased UEBP content 6.6-fold in vivo. Castrated males revealed a marked responsiveness to T and GH in vivo and in vitro, when added separately or in combination. The results obtained suggest a complex regulatory system and we conclude that T acts directly on rat liver as: (1) an inducer of sex differentiation; and (2) a regulator of UEBP production in males. In addition, liver regeneration studies in castrated-hypophysectomized males revealed the UEBP phenotype in daughter cells in the absence of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

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)

Animals↗
PubMed1991

[The cellular localization of the unusual estrogen-binding protein in the liver of rats under different hormonal states].

The localization of an unusual estrogen-binding protein (UEBP) was studied in the rat liver using indirect immunoperoxidase reaction in intact rats and after different hormonal influences. The distribution of the UEBR in normal males displays a form of a gradient with the maximum near the central veins. The gradient is absent in normal females. Castration or hypophysectomy of males, or their injection with estradiol or triiodyronine leads to a decrease in the UEBP concentration, though the gradient character of its distribution is persisting. There is a stable increase in the UEBP concentration in the first two layers of cells adjacent to the central veins in the female rat liver after ovariectomy and especially in combination with androgen injections. The revealed changes in the intensity of immunoperoxidase reaction after different hormonal influences correlate with the UEBP concentration in liver studies performed by the radioligand assay.

Animals↗
PubMed1991

[The characteristics of the programming action of androgens on the formation of sexual dimorphism in the level of corticosteroid-binding globulin in rats].

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.

Aging↗
PubMed1991

[Regularities in androgen reception in rat liver and its role in realizing direct androgenous effects].

The content of androgen receptors (AR) in the cytosol and nuclear fractions of rat liver cells was studied by using the radioligand method. It was found that the nuclear AR content depends on the sex of animals as well as on the initial level of AR in the cytosol fraction. Elevation of AR concentration (p less than 0.05) in liver nuclei of different groups of animals was noted one hour after injection of 100 micrograms of methyltrienolone (R-1881). This elevation correlated positively with the initial level of AR in the cytosol. The accumulation of AR in liver nuclei was more pronounced in intact males than in females. A direct positive correlation between the initial level of cytosol AR and the final regulatory effect of androgens on the hepatic AR content (r = 0.955, n = 6, p less than 0.02) and on the content of the hepatic unusual estrogen-binding protein (UEBP) (r = 0.957, n = 9, p less than 0.001) were found. It is concluded that androgens induce in liver nuclei the accumulation of AR whose level correlates with that of the initial cytosolic AR. The latter reflects the efficiency of the direct effect of androgens on liver cells.

Animals↗
PubMed1990

[Mediate mechanism of positive effect of estrogens on the level of corticosteroid-binding globulin in rats].

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.

Adrenalectomy↗
PubMed1990

In vivo and in vitro estimations of the direct effect of estrogen on rat hepatocytes tested by the changes in the unusual estrogen-binding protein content.

The direct effect of estradiol (E2) on the hepatocytes of mature male rats has been examined by measuring the changes in the unusual estrogen-binding protein (UEBP) content and parallel measuring the level of liver estrogen receptors (ER). The content of UEBP (NUEBP) and ER (NER) in the liver were determined using the quantitative methods for differential specific determination of the E2-binding sites of these proteins. It has been shown that the administration of E2 in vivo induced a considerable decrease in hepatic NUEBP not only in intact males, but also in hypophysectomized males during the initial period after the operation (when the content of hepatic ER was still high) and produced no effect in hypophysectomized males during the later period (when liver ER were depleted). Repeated administration of human growth hormone (hGH) (twice a day) resulted in a considerable increase in NER in hypophysectomized males and restored the sensitivity to the subsequent inhibitory effect of E2 on UEBP. We also used rat hepatocytes after a 4-day primary culturing. These cells had a stable morpho-functional status, high ER level, and sex-differentiated UEBP content. Culturing of mature male rat hepatocytes in the medium containing E2 at concentrations close to physiological levels (10(-10)-10(-7) M) decreased NUEBP in a dose-dependent manner. Hexestrol (10(-7) M) but not cholesterol (10(-5) M) also exhibited a direct effect on NUEBP in cultured rat hepatocytes. The effect of E2 was reversible: statistically significant increase in NUEBP was observed 3 days after 10(-9) M E2 had been removed from the culturing medium. It was concluded that hepatocytes may be a primary target for E2 under physiological conditions and that GH may modulate the direct effect of E2 at the hepatic level by modifying the content of liver ER.

Animals↗
PubMed1990

[The hormonal mechanisms of the programming and regulation of liver function differentiation by sex].

Crucial role of androgens and estrogens in programming and regulation of the sex-dependent expression of a specific estrogen-binding protein, androgenous and estrogenous receptors and corticosteroid-binding globulin, was shown. Both types of the sex steroids effects were shown to be realized in the hepatocytes through respective hormonal receptors. The realization of physiological effects of the sex hormones demands the participation of STH as a permissive factor. Some theoretical and practical aspects of the sex differentiation of the liver functions, are discussed.

Androgens↗
PubMed1990

[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].

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.

Angiotensinogen↗
PubMed1990

[17 Beta-estradiol interaction with haptoglobin and its complex with hemoglobin].

The estradiol-binding capacity of sheep haptoglobin and its complex with hemoglobin was investigated. It was shown that in the presence of H2O2 the haptoglobin-hemoglobin complex tightly binds 17 beta-estradiol. No dissociation of the estradiol-protein complex occurs after its precipitation with trichloroacetic acid and steroid extraction with the ester. It is supposed that the 17 beta-estradiol is bound to the protein by covalent bonds; this binding is characteristic only of the haptoglobin-hemoglobin complex but not of haptoglobin alone.

Animals↗
PubMed1990

[The effect of androgens and somatotropic hormone on the expression of the level of special estrogen-binding protein in the hepatocytes].

The possibility of direct androgen determination of high unusual estrogen-binding protein (UEBP) level in female rat hepatocytes to the level typical to the males was studied. The direct effect of androgen (A) on the UEBP content in hepatocytes of ovariectomized female rats was shown by estimation in vivo and on hepatocyte culture. It has been revealed that the permissive action of growth hormone (GH) is necessary for normal expression of direct androgen effect. The latter has been stable after cessation of hormone action. High concentration of GH was found to possess positive regulatory effect on the UEBP in hepatocytes of ovariectomized rats. Effect of GH quickly disappeared after hormone withdrawal and was under negative regulation by physiological concentrations of A. It was concluded that A owing to its direct action together with permissive influence of GH is capable of determining stable expression of male phenotype of the UEBP level in hepatocytes of females.

Animals↗
PubMed1990

[Sex differences in the level of cytosol estrogen receptors in the rat liver].

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.

Animals↗
PubMed1989

[Studies on tissue distribution of unusual estrogen-binding protein in rats with the help of immunoblotting].

Tissue distribution in male and female rats of unusual immunoreactive material specific for the hepatic estrogen-binding protein (UEBP) was studied by means of immunoblotting analysis. From 28 organs and tissues studied only the liver of animals of both sexes was found to contain polypeptide with Mr, close to Mr of purified UEBP (approximately 31,000), which reacts with anti-UEBP specific antiserum. Detection of the immunoreactive material in female liver, which does not contain any hormone-binding activity of UEBP, suggests pre- or posttranslational modifications of the protein. It is concluded that the regulatory action of UEBP on steroid biodynamics bears a narrow-directed, organ-specific character.

Animals↗
PubMed1988

[Molecular and hormone-binding properties of a partially purified preparation of androgen receptors from the liver of male rats].

Liver cytosol of mature male rats was found to contain androgen receptors (AR). These AR were purified 7--10-fold, and their molecular and hormone-binding properties were investigated. It was found that the AR molecules have a sedimentation coefficient of 9.3 +/- 0.15 and 4.7 +/- 0.11 S, Stokes radius of 6.5 +/- 0.25 and 3.2 +/- 0.08 nm, Mr of 263000 and 65700 Da and friction coefficient ratio of 1.55 and 1.22 for low and high ionic strength media, respectively. The values of rate constants of [3H]methyltrienolone (R1881) association with AR and for the dissociation of the complexes formed are equal to (0.66 +/- 0.29). .10(5) M-1 s-1 and to (0.68 +/- 0.08).10(-5) s-1, respectively, whereas those of equilibrium association constant--to (1.4 +/- 0.3).10(9) M-1 at 0-4 degrees C. It was shown that R1881, 5 alpha-dihydrotestosterone and testosterone strongly compete with 3H-R1881 for the binding with AR (as can be judged from the relative competitive activity of 35 nonlabeled hormonal agents); 19-nortestosterone and delta1-testosterone are more weak, whereas 5 alpha-androstandiols, some hydroxy derivatives of testosterone, cyproterone acetate, estradiol and progesterone are moderate competitors. Other natural testosterone, estradiol and progesterone metabolites as well as corticosteroids do not compete or weakly compete with 3H-R1881 for the binding to AR. It is concluded that the properties of AR are similar to those of classical type AR and that they can intermediate most of the direct effects of androgens on the liver.

Androgens↗
PubMed1987

[Identification of receptors in a system of functionally heterogeneous proteins specifically bound to androgens in rat liver cytosol].

The methods of androgen receptor (RA) isolation and identification in rat liver cytosol were studied. It was shown that male rat liver contains a system of specific androgen (A)-binding proteins consisting of at least three main components: RA, delta 4-androstendione (delta 4-A)-binding component and an unusual estrogen-binding protein interacting also with A and the first two components in females. The identity of one of A-binding components to RA was proved by cumulative properties of this component which are similar to those of RA from other tissues. These properties are as follows: 1) high values of apparent association constant, Ka, for 3H-R1881 (2.8 +/- 0.3 X 10(8) M-1) and 3H-5 alpha-dihydrotestosterone (3H-DHT) (5.0 +/- 0.4 X 10(8) M-1); 2) low binding capacity--approximately 10 fmol/mg of protein of nonfractionated cytosol; 3) pronounced specificity of affinity for active A (DHT, R1881, testosterone); 4) large size of the protein molecule (6.5 +/- 0.25 nm); 5) ability to decrease this size to 3.2 +/- 0.08 nm in a high ionic strength buffer; 6) precipitation at low concentrations of ammonium sulfate: 7) strong interaction with heparin-Sepharose. The properties of the delta 4-A-binding component do not coincide with those of RA: it has a low Ka for 3H-delta 4-A (1.15 +/- 0.5 X 10(6) M-1), a high binding capacity (1.22 +/- 0,12 pmol/mg of protein of nonfractionated cytosol) and can bind various delta 4-3-ketosteroids irrespective of the degree and nature of their biological activity. It was concluded that preliminary isolation of rat liver RA on heparin-Sepharose can be used for differential identification and characterization of this protein.

Androgen-Binding Protein↗