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Biomedical subjects

A G Gunin

Publications and source records attributed to A G Gunin.

At least 19 recordsLinked to original sources
PubMed2004

Effects of peroxisome proliferator activated receptors-alpha and -gamma agonists on estradiol-induced proliferation and hyperplasia formation in the mouse uterus.

It is suggested that the action of peroxisome proliferator-activated receptors (PPARs) cross-talks with estrogen signaling in the uterus. However, it is not known how PPAR agonists affect estrogen-dependent processes in the uterus, especially proliferation and morphogenetic changes. The effects of agonists of PPAR-alpha and -gamma on proliferative and morphogenetic reactions in the uterus under short- and long-term estrogen treatments were therefore examined. Ovariectomized mice were treated with estradiol dipropionate (4 micro g/100 g, s.c., once a week) or vehicle and rosiglitazone (PPAR-gamma agonist) or fenofibrate (PPAR-alpha agonist) or with no additional treatment for 2 days or for 30 days. Treatment with estradiol and PPAR agonists for 2 days did not affect uterine mass. In mice treated with estradiol and rosiglitazone for 2 days, proliferation was enhanced and levels of estrogen receptors-alpha and beta-catenin were decreased in all uterine tissues. Treatment with estradiol and fenofibrate for 2 days had the opposite effects on the parameters tested. In animals treated with estradiol and rosiglitazone for 30 days, uterine mass was increased, abnormal uterine glands and atypical endometrial hyperplasia were found more often and levels of estrogen receptors-alpha and beta-catenin were decreased. In animals treated with estradiol and fenofibrate for 30 days, uterine mass was decreased, most of the uterine glands had a normal structure, no cases of atypical hyperplasia were diagnosed, proliferative activity was declined and the levels of estrogen receptors-alpha and beta-catenin were markedly higher. Treatment with rosiglitazone or fenofibrate did not affect the serum estradiol level in the mice which received estradiol together with PPAR agonists for 30 days. Thus, rosiglitazone exerted the proliferative and morphogenetic effects of estradiol, but fenofibrate had the opposite effect. The actions of rosiglitazone and fenofibrate are associated with changes in the expression of estrogen receptors-alpha and beta-catenin in the uterus.

Animals↗
PubMed2002

Effect of adrenocorticotrophic hormone on the development of oestrogen-induced changes and hyperplasia formation in the mouse uterus.

The aim of this study was to examine the role of adrenocorticotrophic hormone (ACTH) in proliferative and morphogenetic reactions in the uterus under continuous oestrogen treatment. Ovariectomized mice received injections of oestradiol dipropionate or vehicle once a week (2 microg per 100 g), and injections of ACTH (10 microg per 100 g) once a day or once a week for 30 days. Additional control mice received oestradiol and saline, vehicle of oestradiol, and ACTH once a day or once a week, or vehicle of ACTH, for 30 days. This study shows for the first time that ACTH affects oestrogen-dependent reactions in the uterus. Treatment with ACTH once a day resulted in a decrease in uterine mass, in cell proliferation (assessed by the number of mitotic and bromodeoxyuridine (BrdU)-labelled cells) and in the incidence of endometrial hyperplasia, in particular complex and atypical hyperplasia. Treatment with ACTH once a week led to a marked reduction in the incidence of endometrial hyperplasia, a slight increase in uterine mass and had almost no effect on cell proliferation. Daily treatment with ACTH reduced the concentration of oestrogen receptor alpha in all uterine compartments, but weekly ACTH administration had the opposite effect. Expression of glucocorticoid receptors, beta-catenin and glycogen synthase kinase-3beta in uterine tissues was lower in animals treated with oestradiol and ACTH once a day or once a week. When olive oil was used instead of oestradiol, treatments with ACTH did not produce detectable changes in all parameters examined. Thus, glucocorticoid receptor, oestrogen receptor alpha, beta-catenin and glycogen synthase kinase-3beta are involved in the effects of ACTH on oestrogen-induced changes in uterine mass, cell proliferation and the incidence of hyperplasia.

Adrenal Glands↗
PubMed2002

Effect of prolactin and dopaminergic drugs on uterine response to chronic estrogen exposure.

The aim of this work was to examine the role of prolactin and dopaminergic drugs, which affect prolactin secretion, on proliferative and morphogenetic reactions in the uterus under continuous estrogen treatment. Ovariectomized mice received injections of estradiol dipropionate (2 microg per 100 g, weekly) or vehicle and daily injections of prolactin (0.25 mg/100 g) or saline (0.05 ml) for 30 days. Other groups of mice received injections of estradiol or vehicle and injections of saline, and were allowed to drink bromocriptine (25 mg/l), metoclopramide (25 mg/l), or only tap water for 30 days. Prolactin administration results in a decrease in the incidence of abnormal glands with abnormal epithelium, the incidence of atypical hyperplasia, uterine weight, proliferation (the number of mitotic and bromodeoxyuridine-labeled cells) and the levels of estrogen receptor-alpha, but causes an increase in the level of beta-catenin in uterine tissues of estrogen-treated mice. The effect of metoclopramide, which increases prolactin secretion, is principally similar to prolactin, but much less expressed. Bromocriptine, which reduces prolactin levels, increases uterine weight, proliferation, the levels of estrogen receptor-alpha, the incidence of abnormal glands with abnormal epithelium, the incidence of complex and atypical hyperplasia, and decreases the level of beta-catenin in uterine structures of estrogen-treated mice. In the absence of estradiol, none of the treatments used had any effect on the parameters tested. Thus, prolactin or metoclopramide produce antiestrogenic effects in the uterus of mice and prevent the formation of atypical hyperplasia which has an unfavorable prognosis, but bromocriptine has the opposite effect. Estrogen receptor-alpha and beta-catenin were associated with the actions of prolactin, metoclopramide and bromocriptine on estrogen-dependent processes in the uterus.

Animals↗
PubMed2001

Estrogen changes mitosis orientation in the uterine epithelia.

OBJECTIVES: Estrogens can lead to hyperplasia and cancer formation in the uterus, ovary and mammary gland. However, key factors involved in this process are not defined at present. It is possible that estrogens primarily affect more global tissue-organising parameters as composition of tissues in three-metric space, that is brought about changes in the orientation of the plane of cell division. There are no data about estrogen action on mitosis orientation in the uterus. STUDY DESIGN: Mitosis orientation, proliferative activity and general histology were examined in the uterus, jejunal and colonic crypts, and epidermis of ovariectomized rats 0, 24, 36 and 48h after a single injection of estradiol, and in the uterus of ovariectomized mice received injections with estradiol once-a-week for 30, 60 and 90 days. RESULTS: All mitoses in luminal and glandular epithelia of the uterus of ovariectomized rats aligned parallel to the basement membrane, and estradiol treatment leads to appearing of mitoses oriented perpendicular to the basement membrane of the epithelium. Together with increase in the proliferative activity, the number of perpendicular oriented mitoses in uterine epithelia of ovariectomized rats is significantly increased after a single injection of estradiol. During endometrial hyperplasia formation in mice, that is induced by chronic estrogen treatment, the number of perpendicular oriented mitoses in uterine epithelia become much more higher. In jejunal and colonic crypts, epidermis of ovariectomized rats, most of mitoses disposed parallel to the basement membrane and an injection of estradiol did not affect mitosis orientation and activity of proliferation. CONCLUSIONS: Estradiol effect on mitosis orientation may be considered as specific. Changes in mitosis orientation are probably responsible for estrogen-dependent hyperplasia and cancer formation in the uterus.

Animals↗
PubMed2001

Proliferation, mitosis orientation and morphogenetic changes in the uterus of mice following chronic treatment with both estrogen and glucocorticoid hormones.

Glucocorticoids have been known to be involved in the regulation of some aspects of estrogen action on the uterus. However, the effect of glucocorticoids on changes in uterine morphogens produced by chronic estrogen exposure is not known. Therefore, the aim of this work was to examine the role of glucocorticoids on proliferative and morphogenetic uterine reactions induced by continuous estrogen treatment. Ovariectomized mice received subcutaneous injections of estradiol dipropionate in olive oil (2 microg per 100 g body weight once a week) or vehicle and drank water with or without dexamethasone (2 mg/l) for 30, 60 and 90 days. Treatment with dexamethasone caused a marked reduction in estradiol-induced changes in uterine weight, in proliferation (estimated from the proportion of mitotic and BrdU-labeled cells in all uterine tissues), and in changes in estradiol-dependent morphogenesis, which was redirected from the formation of atypical hyperplasia in animals receiving only estradiol to the appearance of simple or cystic endometrial hyperplasia in animals receiving both estradiol and dexamethasone. Estradiol alone increased dramatically the number of perpendicular oriented mitoses in luminal and glandular epithelia, and administration of dexamethasone inhibited this effect. In the absence of estradiol, chronic treatment with dexamethasone has no effect on all uterine parameters tested. Thus, chronic glucocorticoid treatment produces a complex antiestrogenic effect in the uterus of mice. Estradiol-induced changes in mitosis orientation are probably responsible for changes in the shape of glands and development of endometrial hyperplasia.

Analysis of Variance↗
PubMed2000

Two month glucocorticoid treatment increases estradiol-induced stromal and myometrial cell proliferation in the uterus of ovariectomized rats.

The present work was undertaken to examine the effect of 2 month glucocorticoid treatment on estradiol-induced proliferation in the uterus. Ovariectomized rats were treated with long-acting triamcinolone acetonide or saline for 60 days followed by a single injection of estradiol dipropionate or vehicle. Proliferation in the uterus was estimated by the mitotic index, bromodeoxyuridine-labelling index and proliferating cells nuclear antigen-labelling index 24, 36 and 48 h after the injection of estradiol or vehicle. Two month glucocorticoid treatment resulted in an initial decrease in all the parameters for luminal and glandular epithelia followed by an increase to 48 h after estradiol injection, and in a large increase in all proliferative parameters for stromal and myometrial cells at all periods of observation, compared with control rats untreated with glucocorticoid. The 2 month glucocorticoid treatment protocol had no significant effect on the parameters without estradiol administration. Analysis of proliferation for myometrial cells was also performed after 1 month treatment with glucocorticoid followed by estradiol or saline. Results showed no significant influence of 1 month treatment with glucocorticoid on myometrial cells.

Animals↗
PubMed2000

Two-month glucocorticoid treatment increases proliferation in the stomach and large intestine of rats.

BACKGROUND/AIMS: It has been shown that acute or short-term treatments with glucocorticoids lead to a marked decrease in proliferation in the stomach and large intestine. The effects of more prolonged glucocorticoid treatment on cell renewal in these organs are not known. The present work was therefore undertaken to examine the proliferative activity in the stomach and colon during 2 months of glucocorticoid treatment in comparison with shorter treatments. METHODS: Rats were treated with either the glucocorticoid triamcinolone acetonide or vehicle for 63, 33 or 3 days. Proliferation was assessed in the glandular epithelium of the fundal part of the stomach and in the epithelium of the colonic crypts using three criteria: the mitotic index; the bromodeoxyuridine labelling index, and the proliferating cell nuclear antigen-labelling index (percentage of mitotic or labelled cells). RESULTS: Treatment with glucocorticoid for 63 days resulted in a very significant increase in all proliferative parameters tested in the gastric mucosa and the colonic crypts. On the contrary, treatments with glucocorticoid for 3 or 33 days had a marked inhibitory influence on proliferation in these tissues. CONCLUSION: As opposed to treatments for 3 or 33 days, glucocorticoid treatment for 2 months leads to an increase in the number of cycling cells in the gastric and colonic mucosae.

Analysis of Variance↗
PubMed1999

Effect of acute and chronic glucocorticoid treatments on epithelial cell proliferation in the esophagus and small intestine of rats.

Data about glucocorticoid influence on proliferation in the esophagus and small intestine are very contradictory and need to be reexamined. Moreover, only the effects of acute or short-term treatments with glucocorticoids have been demonstrated, whereas nothing is known about their effects under chronic exposure. This work was therefore carried out to examine proliferative activity in the esophagus and small intestine under conditions of acute and chronic glucocorticoid exposure. Rats were treated with either glucocorticoid triamcinolone acetonide or vehicle for 3, 33, or 63 days. Proliferation was assessed in the basal layer of esophageal epithelium and in the epithelium of jejunal crypts, using three criteria, as the number of mitotic, bromodeoxyuridine-labelled, and proliferating cell nuclear antigen-labelled cells. Treatment with glucocorticoid for 3 days led to a slight decrease in all parameters in the esophageal epithelium and had almost no effect on proliferation in the epithelium of jejunal crypts. Long-term treatment with glucocorticoid for either 33 or 63 days resulted in an increase in all parameters tested in both esophageal and jejunal crypt epithelia. Sixty-three-day treatment had a more prominent and significant (P < 0.05) effect. These results suggest that acute glucocorticoid treatment nonsignificantly reduces the number of cells in the cell cycle in the esophageal epithelium, whereas chronic treatment increases the number of proliferating cells in both esophageal and jejunal crypt epithelia.

Animals↗
PubMed1998

Role of mast cells in oestradiol effects on the uterus of ovariectomized rats.

The role of mast cells and their main secretory products in the effects of oestradiol on the uterus was investigated. Ovariectomized rats were treated with a single injection of oestradiol (10 micrograms per rat, i.m.) or vehicle together with drugs affecting the activity of mast cells, cromoglycate (10 mg per rat, i.m.), which diminishes the degranulation of mast cells, or compound 48/80 (0.5 mg per rat, i.m.), which enhances this process. Oestradiol or vehicle was also administered with two important secretory products of mast cells, heparin (0.4 mg per rat, i.m.) or histamine (2 mg per rat, i.m.). All drugs were injected simultaneously with oestradiol (first injection) and then every 6 h until the animals were killed. Observations were performed at 24, 36 and 48 h after oestradiol or vehicle injection. The condition of mast cells was determined by the percentage of degranulated mast cells in sections stained with toluidine blue. Oestradiol-induced effects in the uterus were estimated by the mitotic index, proliferating cell nuclear antigen-labelling index, DNA content, volumes of cells, nuclei and nucleoli in the luminal epithelium, glandular epithelium and stroma cells of the endometrium. Cromoglycate treatment resulted in a decrease in both mast cell degranulation and all examined oestradiol effects in the uterus at all periods of observation. Compound 48/80 increased mast cell degranulation and expression of one aspect of oestradiol effects on the volumes of cell compartments. Histamine or heparin led to a marked increase in the cell, nucleus and nucleolus volumes in all uterine structures. However, heparin produced a depression in proliferation, whereas histamine had a weak transient stimulating action on this process. No effects of the protocols were found in the absence of oestradiol treatment. These results suggest that mast cells are involved in the realization of oestrogen action, including the stimulation of cell growth and proliferation in the uterus, and that the effect of mast cells is mediated by both histamine and heparin.

Analysis of Variance↗
PubMed1998

Effect of long-term glucocorticoid treatment on oestradiol-induced proliferation in the uterus of ovariectomized rats.

The aim of this study was to examine the effect of long-term treatment with glucocorticoids on the uterine response to oestradiol. Ovariectomized rats were treated with crystal triamcinolone acetonide (0.1 mg/100 g, i.m.) or saline (0.1 ml/100 g i.m.) for 29 days. Over this period five injections were administered, one per week. On the second day after the last triamcinolone injection, rats were treated with a single injection of oestradiol dipropionate (5 micrograms/100 g, s.c.) or vehicle (olive oil, 0.1 ml/100 g, s.c.). The effects of oestradiol in the uterus were determined by measuring mitotic index, bromodeoxyuridine (BrdU)-labelling index (BrdU was injected 2 h before the rats were killed; 2 mg/100 g, i.p.), and proliferating cell nuclear antigen (PCNA)-labelling index 24, 36 and 48 h after the injection of oestradiol or vehicle. Long-term treatment with glucocorticoids resulted in dissimilar changes in oestradiol-induced proliferation in epithelial and connective-tissue (stroma) components of the uterus. In luminal and glandular epithelia, there was an initial reduction in proliferation at 24 h, followed by an increase at 36 h and a further reduction at 48 h after the oestradiol injection. In stromal cells of the endometrium, triamcinolone treatment caused a large constant increase in oestradiol-induced proliferation throughout the experiment. The glucocorticoid treatment had no effect on the parameters without oestradiol administration.

Analysis of Variance↗
PubMed1997

Influence of growth hormone on the uterine response to oestradiol in rats.

The aim of this study was to examine the effect of growth hormone on the uterine response to oestradiol. Ovariectomized rats were treated with a single injection of oestradiol dipropionate (10 micrograms per rat, i.m.), together with a single injection of human growth hormone (0.04 mg per rat, i.m.). The effects of oestradiol in the uterus were determined by measuring the following: mitotic index; the percentage of cells positive for the proliferating cell nuclear antigen (using immunocytochemistry); the DNA content (using Feulgen's method); and the volume of cells, nuclei and nucleoli (using morphometry) in the luminal epithelium, glandular epithelium and stroma of the endometrium 24, 36 and 48 h after injection with oestradiol. All values for all structures were decreased after oestradiol and growth hormone treatment compared with values of rats treated with oestradiol only. However, parameters that reflected proliferative processes (mitotic indices, the number of cells positive for proliferating cell nuclear antigen, and DNA content) were much more reduced than those indicating cell growth (volumes of cells, nuclei and nucleoli). In the absence of oestradiol, administration of growth hormone did not influence the uterine parameters tested. The effect of growth hormone is likely to be brought about by changing the mechanism of oestrogen action on the uterus.

Analysis of Variance↗
PubMed1997

Effect of heparin on oestradiol-induced cell growth and proliferation in the uterus of ovariectomized rats.

The aim of this study was to examine the role of heparin in the realization of oestradiol (OE2) effects in the uterus. Ovariectomized rats were treated with a single injection of OE2 dipropionate (10 micrograms/rat, i.m.) along with injections of heparin (in doses of 0.4 mg/rat, i.m.). OE2 effects in the uterus were determined by measuring mitotic indices, proliferating cell nuclear antigen (PCNA)-labelling indices, DNA content, and volumes of cells, nuclei and nucleoli in luminal and glandular epithelia and stromal cells of the endometrium 24, 36 and 48 h after the injection of OE2. Heparin treatment inhibited the OE2-stimulated increase in mitotic activity and DNA content of the uterine structures, whereas OE2-induced increases in cell, nucleus and nucleolus volumes in all uterine structures tested at all the times were greatly augmented by heparin. The OE2-induced increase in PCNA-labelling index in all the cell types had a tendency to increase as the result of heparin action. In the absence of OE2, heparin had no effect on any of the uterine parameters. The effect of heparin is probably realized via changes in the mechanism of oestrogen action in the uterus. Heparin probably prevents passage of the cells from the G1- to the S-phase of the cell cycle and prolongation of the G1-phase with consequent accumulation of the cells in this phase of the cell cycle. This probably leads to reduction of mitotic activity. Furthermore, cells in G1-phase probably prolong their biosynthetic processes causing enlargement of the cell, nucleus and nucleolus volumes.

Animals↗
PubMed1996

The role of prolactin in realization of estradiol action in the uterus of ovariectomized rats.

The aim of this study was to examine the role of prolactin (PRL) in promoting the effects of estradiol (E2) on the uterus. Ovariectomized rats were given a single injection of E2 dipropionate (10 micrograms/rat), along with injections of ovine prolactin (PRL; a single dose--2.5 IU/rat), or injections of metoclopramide (a single dose--0.5 mg/rat), or injections of bromocriptine (a single dose--0.25 mg/rat). The effects of E2 on the uterus were determined by measuring mitotic indexes; cell, nucleus and nucleolus volumes (morphometry), and DNA content (Feulgen's method) in luminal and glandular epithelia, endometrial stromal cells at 24, 36 and 48 h after the injection of E2. It is revealed that at each time point after E2 and PRL or metoclopramide treatment almost all the tested parameters were lower than those in control rats treated with E2 and distilled water. The values obtained in all the periods after E2 along with bromocriptine treatment were higher compared with those in E2-treated animals. Most of the results are statistically significant (P < 0.05-0.001). In the absence of E2 none of the drugs used influenced the uterine parameters tested. The effect of PRL is likely to be mediated by their receptors in the uterus, and it occurs by changing the mechanism of estrogen action in the uterus. The actions of metoclopramide and bromocriptine are probably also mediated by PRL.

Analysis of Variance↗
PubMed1996

Effect of chronic stress on estradiol action in the uterus of ovariectomized rats.

The aim of this study was to investigate the development of estradiol (E2) effects in ovariectomized rat uterus under chronic stress. The chronically stressed rats (swimming and overcrowded cages) were treated with a single injection of E2 dipropionate (10 micrograms/ rat, i.m.) in olive oil (0.1 ml/rat). Control groups of ovariectomized rats included one group treated with the same dose of E2 but maintained in stress-free conditions, a second group subjected to the same procedure of chronic stress but injected with olive oil only, a third group treated with olive oil and maintained in stress-free conditions, and a final group which consisted of uninfluenced ovariectomized rats. E2 effects were determined by measuring activity of proliferation (mitotic index), cellular, nuclear, and nucleolar volumes (morphometry), DNA content (Feulgen's method) in luminal and glandular epithelia, stromal cells of endometrium at 24, 36 and 48 h after injection of E2 or olive oil. In chronically stressed rats treated with E2, at each time point almost all the parameters in all the structures were significantly (P < 0.05-0.001) higher, than in unstressed E2-treated rats. In E2-untreated rats, the stress did not influence uterine tissues. Thus, the chronic stress enhances strongly the E2-induced effects in the uterus of ovariectomized rats. It is likely mediated by the changes of some steps in the mechanism of estrogen action that leads to the increase in the sensitivity of uterine structures to estrogens.

Animals↗
PubMed1990

[Granular biogenic amine-containing cells of the rat endometrium as components of the system of mononuclear phagocytes].

To 10 non-inbred white mature rats 24 h before sacrifice 7.0 ml of Indian ink colloid solution has been injected intraperitoneally. Histochemical reactions of Falk-Hillarp (catecholamines, serotonin) have been performed on nonfixed cryostat slices of the uterus, those of Cross, Even, Rost (histamine) against non-specific esterase and acid phosphatase. Before carrying out these reactions, the slices have been examined under luminescent microscope LUMAM-I3 by means of luminescent and usual illumination in order to reveal cells, possessing autoluminiscence and containing phagocyted Indian ink particles. Presence of autoluminescence, phagocyted material, catecholamines and serotonin, histamine, nonspecific esterase, acid phosphotase, prostaglandin E2 in the same granular cells of the rat endometrium have been stated. All cellular properties revealed are specific for macrophages. A conclusion is made that granular biogenic amine-containing cells of endometrium can be considered as belonging to the system of mononuclear phagocytes.

Animals↗
PubMed1989

[Histamine distribution in the uterine structures of ovariectomized rats administered estradiol, histamine antagonists and an inhibitor of prostaglandin synthesis].

In the experiments performed on ovariectomized rats, using luminescent-histochemical method for revealing histamine after Cross, Ewen and Rost, it has been demonstrated that estradiol facilitates increasing histamine content in the uterine structures, as well as its redistribution--histamine content increases in the glandular and tegmental epithelia, in stromal cells, smooth myocytes and it decreases in macrophages. These manifestations of estradiol action are absent after cymetidin and indometacin, but not tavegil administration. The first two inhibit the morphological effect of estradiol in the uterus, indometacin making it in a greater degree. It is supposed that estradiol action, concerning provision of the uterine structures with histamine, takes place together with prostaglandins participation and at hormonal activation of H2-receptors. Taking into account the literature data on stimulating influence of estradiol on macrophagal phagocytosis and secretion, a conclusion is made that decreasing content of histamine in macrophages at estrogenization results from histamine release by these cells; macrophages are potential sources of histamine in the uterus.

Animals↗
PubMed1988

[Localization of histamine in uterine structures].

By means of luminescent-histochemical method of Cross, Even, Rost histamine is revealed in all uterine structures. Visual and fluorometric data demonstrate uneven distribution of histamine in the organ's structures. A high content of histamine is specific for macrophages and mast cells, less high--in tegmental epithelium and endometrial glands. A low level of histamine have endometrial stroma, smooth myocytes, cells of the serous membrane and vessels. Basing on the literature data, concerning various sensitivity of the uterine tissues to estrogens and regarding effect of the estrogens upon histamine metabolism in the uterine and regarding interconnection of the histamine receptors in the uterus and the estrogens, a suggestion is made that various contents of histamine in the uterine structures depend on various amount of the histamine receptors in them and on different abilities of the uterine tissues to inactivate histamine. The ability of macrophages to accept free forms of bioamines, as it is described in the literature, evidently can be spread to the uterine macrophages, where a high content of histamine is revealed.

Animals↗