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Biomedical subjects

A G Reznikov

Publications and source records attributed to A G Reznikov.

At least 19 recordsLinked to original sources

[Sex characteristics of neuroendocrine effects of prenatal exposure to exogenous glucocorticoids].

The effects of hydrocortisone acetate treatment of rats during the last gestational week on neurochemical and morphological characteristics of the brain in early postnatal and mature offspring were studied. Disappearance of sexual differences both in aromatase and 5alpha-reductase activities and noradrenaline concentration in the preoptic area in 10-day old rats was found. Meanwhile a sexual dimorphism in serotonin metabolism emerged. In adult offspring, the prenatal exposure to glucocorticoids resulted in disappearance of sexual differences in neurocytes' nuclei volume in medial preoptic and suprachiasmatic nuclei. The adrenocortical reaction to noradrenaline infusion to the 3rd brain ventricle was absent in the experimental males and intensified in females. In males, adrenocortical reaction to restraint decreased while post-stress changes in hypothalamic noradrenaline concentration and hippocampal glutamate decarboxylase activity were not observed. In the similar experiments in females both the augmentation of adrenocortical reaction and inhibition of GABA-ergic system were revealed. The results obtained indicate the modifying effect of prenatal exposure to glucocorticoids on sexual dimorphism of neuroendocrine system.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Early postnatal effects of prenatal exposure to glucocorticoids on testosterone metabolism and biogenic monoamines in discrete neuroendocrine regions of the rat brain.

We investigated the effects of hydrocortisone acetate and dexamethasone administered to pregnant rats during the last gestational week on sexual differentiation of testosterone metabolism and biogenic monoamine contents and turnover in the discrete brain regions in 10-day-old offspring. In the preoptic area, sex-dependent differences in aromatase activity were attenuated by prenatal glucocorticoids. Prenatal dexamethasone but not hydrocortisone acetate caused the inversion of sexual dimorphism of 5alpha-reductase activity in the preoptic area. In the brain preoptic area of the male pups prenatally exposed to hydrocortisone acetate, a decrease in noradrenaline turnover was found. Dopamine turnover in the preoptic area and 5-hydroxytryptamine metabolism in the preoptic area and medial basal hypothalamus increased in females as a result of hydrocortisone acetate treatment. Our results indicate that excess glucocorticoids in prenatal life modifies the basic neurochemical and neurophysiological mechanisms of sexual brain differentiation and might contribute to behavioral and reproductive disorders in adulthood.

Animals↗

Developmental changes in the distribution of corticosteroid-binding globulin in fetal and newborn sheep tissues.

Developmental changes in immunohistochemical localization of corticosteroid-binding globulin (CBG) in fetal and newborn sheep tissues were studied. Tissue samples have been harvested at days 63-64, 100-103, 125-128 and 142-144 of gestation or 2 postnatal days. In the liver, immunoreactive CBG (irCBG) has been identified in hepatocytes. The intensity of CBG staining was highest at 63-64th gestation days and then was lowered gradually down to negligible level in newborn lambs. Within kidney, irCBG was selectively localized to the epithelium of proximal and distal convoluted tubules. Its amount in the course of development followed a pattern similar to that in the liver. By contrast, fetal sheep lung and pancreas demonstrated noticeable rise of irCBG late in gestation. irCBG has been detected in respiratory epithelium of tertiary bronchi, bronchioles and terminal bronchioles, meanwhile alveoli and other lung tissues were CBG-immunonegative. In the pancreas, irCBG staining was associated with acinary cells, whereas Langerhans islets contained no irCBG at all examined stages of pregnancy. Developmental changes in irCBG did not follow reported triphasic profile of fetal sheep plasma CBG concentrations thereby showing the existence of independent cellular mechanisms regulating CBG level in the tissues. Peculiarities of intraorgan distribution and developmental changes in irCBG suggest that intracellular CBG may regulate bioavailable cortisol concentrations in the sheep tissues during fetal and early postnatal life.

Animals↗

Participation of endogenous opioids in pathogenesis of early neuroendocrine manifestations of prenatal stress syndrome.

We studied sex dimorphism in the content of norepinephrine and activity of enzymes involved in testosterone metabolism in the preoptic hypothalamic area of 10-day-old rats. Prenatal stress eliminated sex-related differences in these indices. These disturbances were absent in rats subjected to prenatal stress under conditions of opioid receptor blockade with naltrexone. These data attests to the important role of opioids in the pathogenesis of prenatal stress syndrome.

Animals↗

Neuroendocrine mechanisms of development of experimental hyperandrogen-induced anovulation.

An experimental model of hyperandrogen-induced anovulatory infertility (s.c. implantation of Silastic capsules containing testosterone into adult female rats) was used to study morphological, hormonal, and biochemical measures characterizing the state of the hypothalamo-hypophyseal-ovarian system. Impairments in functional androgen metabolism in the hypothalamus were seen, with decreases in the Luliberin sensitivity of the hypophysis, changes in the structure of estral cycles, and morphological changes in the ovaries; these findings are evidence for neuroendocrine disturbances in the control of ovulation. Flutamide, an experimental antiandrogen, led to partial normalization of the hormonal, biochemical, and morphological characteristics, as well as to recovery of fertility in females with anovulatory infertility.

Androgen Antagonists↗

Endocrine mechanisms of suppressive effect of low dose estrogen-antiandrogen treatment on androgen-dependent organs of male rats.

The effects of low doses of hexestrol (Hex) (2-40 micrograms/kg bw) and flutamide (FI) (10 mg/kg bw) on some endocrine mechanisms in mature intact male rats are described in the present paper. It has been shown that each preparation, administered separately for 10 days, induced a moderate decrease in the weight of the ventral prostate (VP), anterior prostate lobe or coagulating gland (CG) and seminal vesicles (SV), in the DNA content and number of cells in the VP. 5 alpha-reductase activity was also decreased; the epithelium secretory activity of the VP was suppressed. After combined FI (10 mg/kg bw) and Hex (40 micrograms/kg bw) the following castration-like effects were observed: an abrupt fall in the weight of the accessory sexual glands, a decrease of DNA level and cell number in the VP as well as a suppression of the production of 5 alpha-reductase metabolites in this structure. Histologically, a marked degenerative changes in the VP secretory epithelium was observed; on the contrary an hyperplasia of connective and smooth muscle cells was evident. When FI alone was administered to rat, the above-mentioned changes were accompanied by a pronounced elevation of plasma bio-LH and testosterone (T) levels, also an increase of testicular delta 5-3 beta-hydroxysteroid dehydrogenase activity was observed. On the contrary, when Hex was administered alone or in combination with FI, bio-LH and T levels and enzyme activity decreased. We conclude that Hex administration in low doses, in combination with FI, could be an alternative method for a complete androgen blockade of the accessory sexual glands.

Androgen Antagonists↗

Early postnatal changes in sexual dimorphism of catecholamine and indoleamine content in the brain of prenatally stressed rats.

Sexual dimorphism in catecholamine and indoleamine content in the brain preoptic area and mediobasal hypothalamus was studied in 10-day-old rat pups whose mothers had been exposed to the daily 1-h immobilization stress during the last week of pregnancy. Concentration of noradrenaline in the preoptic area and 5-hydroxyindoleacetic acid in the mediobasal hypothalamus of the prenatally stressed male offspring as well as dopamine content in the mediobasal hypothalamus and 5-hydroxyindoleacetic acid content in the preoptic area of the females were increased by 59%, 45%, 34%, 76%, respectively. Dopamine content in the preoptic area of the female pups was decreased. In addition, an increase of 5-hydroxytryptamine metabolism in the female preoptic area has been revealed. As a result of prenatal stress, sex-related differences in noradrenaline and 5-hydroxyindoleacetic acid concentrations in the preoptic area and those in dopamine concentration in the mediobasal hypothalamus disappeared. The suggestion is made that the early changes in sexual dimorphism of the brain catecholamines and 5-hydroxytryptamine metabolism in prenatally stressed rats may be responsible for the development of the long-term disorders of sexual differentiation of the neuroendocrine functions.

Animals↗

[The effect of prenatal stress on the development of hypophyseal gonadotropic function in male rats].

Significant changes of the aromatase and 5 alpha-reductase hypothalamic activity were found in juvenile prenatally stressed male Wistar rats. The blood plasma testosterone level increased following niftolide (NF) or 1, 4, 6-androstatine-3, 17-dione (ATD) administration. Prenatal stress seems to exert a modifying effect upon the regulating mechanisms of the pituitary gonadotropin function, lowering the functional reserves of the hypothalamo-hypophyseal-testicular axis in pre- and postpubertal male rats.

Androgen Antagonists↗

Catecholamines in steroid-dependent brain development.

UNLABELLED: Sex-specific peculiarities of catecholamine (CA) content and turnover in neuroendocrine brain areas and their modification with neonatal steroids or prenatal stress (PS) in Wistar rats were studied. No changes in noradrenaline (NA) content and turnover rate were found in the preoptic area (POA), meanwhile dopamine (DA) turnover rates in the POA and mediobasal hypothalamus (MBH) were increased in neonatally androgenized 10-day-old females. Treatment of female neonates with various catecholestrogens increased hypothalamic NA content by 30-95% but only 4-hydroxyestradiol-17 beta induced anovulation. 6-Hydroxydopamine had no significant impact on hypothalamic CA content in neonates and did not prevent testosterone-induced persistent estrous. Maternal stress (restriction for 1 h a day, 15-21st days of pregnancy) resulted in a decrease of hypothalamic NA and blood plasma corticosterone response to acute stress in adult male offspring. Sex differences in CA content in the POA and MBH disappeared in 10-day-old prenatally stressed rats. CONCLUSIONS: (1) sexual brain differentiation needs co-operative actions of sex steroids and CA to be completed; and (2) early changes in CA content and turnover induced by PS or neonatal steroid exposure predetermine long-term alterations of the stress responsiveness, reproductive behaviour and neuroendocrine control of ovulation.

Animals↗

Effects of neuropeptide Y on gonadotropin and prolactin release in normal, castrated or flutamide-treated male rats.

This study was carried out to clarify the central effects of neuropeptide Y (NPY) on gonadotropin and prolactin (PRL) release in the male rat and to evaluate the hypothesis that it may play a role in negative feedback regulation of gonadotropin secretion in the male. NPY (4 micrograms in 2 microliters 0.9% NaCl) or an equal volume of saline was microinjected into the third cerebral ventricle of conscious, unrestrained rats and its effects on plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH) and PRL concentrations, and the gonadotropin response to LH-releasing hormone (LHRH) were measured by radioimmunoassay in noncastrated, castrated (3 days before the experiment) rats or animals treated with flutamide, an androgen receptor blocker (10 mg/kg b.w. per day subcutaneously for 3 days). Blood samples were drawn periodically from a Silastic catheter in the external jugular vein just before and for 120 min after intraventricular injections. At 90 min after injection 25 ng of LHRH were infused intravenously and 3 additional blood samples were withdrawn at 10-min intervals after the injection. Normal male rats responded to NPY with a decrease in plasma LH concentrations at 60 min. Plasma LH was significantly lower at 120 min than values in the saline-injected controls. At that time there was a significant 2-fold augmentation of their response to LHRH. In contrast, NPY elevated plasma FSH significantly versus values in controls at 15 and 30 min after injection, but the FSH release in response to LHRH was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Augmentation of the sterilizing effect of neonatal androgenization with tropolone, a catechol-O-methyltransferase inhibitor, in female rats.

The influence of tropolone, a catechol-O-methyltransferase (COMT) inhibitor, on the sterilizing effect of neonatal testosterone propionate (TP) has been studied in Wistar female rats. Tropolone-induced changes in COMT activity and noradrenaline (NA) and dopamine (DA) contents in the hypothalamus have been evaluated. Inhibition of COMT activity was maximal 3 h after a single injection of 0.6 mg tropolone on postnatal day 5. An increase in DA level was observed 6 h after drug injection, whereas the NA content was elevated 24 h after tropolone administration. A sexual dimorphism in hypothalamic NA content in rats was found on postnatal day 10: it was higher in males than in females. The rise of catecholamines in the hypothalamus of 10-day-old female rats induced by COMT inhibition with tropolone (0.3 mg on postnatal days 5 and 7) was unable to masculinize developing neuroendocrine regions responsible for sexual cyclicity. At the same time, combined administration of tropolone (0.1 mg daily on postnatal days 4-10) and TP (0.025 mg on day 4) enhanced the sterilizing effect of the androgen. An anovulatory sterility appeared in all experimental animals. It is suggested that a cooperative interaction occurs between catecholamines and sex steroids as determinants of brain sexual differentiation.

Animals↗

[Increase of noradrenaline contents in the hypothalamus of neonatal female rats under the effects of 4-hydroxyestradiol-17beta].

Catecholamine content was studied in hypothalamus of neonatal Wistar female rats treated with 4-hydroxyestradiol-17 (4-OH-E2) in a dose of 10 mg for 1-5 days of life. 4-OH-E2 induced a reliable increase in hypothalamic noradrenaline level in 24 h after the last injection, but not on the 7th, 10th or 12th postnatal days. There was no change in dopamine level. We have postulated a relationship between the increase in hypothalamic noradrenaline content induced by 4-OH-E2 and defeminization effects of 4-OH-E2 on the developing brain of female rats.

Age Factors↗

[Uptake of testosterone by tissues of human fetal prostatic rudiments].

The common and specific uptake of 3H-testosterone (3H-T) by tissues of urogenital sinus (UGS) and bladder (BL) in human 10-12 weeks fetuses was studied. The values of common and specific 3H-T uptake in UGS were significantly higher than those in BL. A high specific uptake of labeled hormone was also detected in UGS mesenchyme separated from epithelium. The authors did not reveal any sexual dimorphism of 3H-T uptake by UGS tissues.

Epithelium↗

[Effect of destruction of the lateral septal nucleus on the hormonal reserves of the hypothalamo-hypophyseo-testicular system].

Presence of a parahypothalamic-adenohypophyseal way of the influence of the lateral septal nuclei (LSN) lesion on the gonads was suggested on the basis of study of hormonal reserves of the hypothalamo-hypophyseal-testicular system in adult male albino rats in experiments using niftolide (flutamide) after the lesion of the LSN, the medial-basal hypothalamus remaining intact or isolated.

3-Hydroxysteroid Dehydrogenases↗

Prevention of the anovulatory syndrome and testosterone-induced rise in catecholamine level in the hypothalamus of newborn rats with steroid aromatase inhibitors.

Testosterone propionate administration in a dose of 50 micrograms on the 5th day of the postnatal life did not change hypothalamic noradrenaline and dopamine levels in female rats on the 7th, 8th, 12th days of life but increased it significantly in 10-day-old animals. This rise was completely prevented by steroid aromatase inhibitors (4-androstene-3,16,17-trione, 0.5 mg or 1,4,6-androstatriene-3,17-dione, 1 mg per animal) on the 5th or 7th days of life. Aromatase inhibitors reduced the anovulatory syndrome occurrence in neonatally androgenized rats from 93% to 15-17%. The data obtained prove the importance of testosterone conversion into estrogen for sexual brain differentiation. They support authors' hypothesis that testosterone-induced rise of hypothalamic catecholamine content in newborn female rats is evoked by the estrogen metabolites of testosterone.

Animals↗

[Effect of steroid aromatase inhibitors on the catecholamine content of the hypothalamus of neonatally androgenized rats].

Administration of 50 micrograms of testosterone propionate to newborn female rats on the 5th day of life provoked a reliable increase in noradrenaline and dopamine concentrations in the hypothalamus of 10-day-old rats. Neonatal administration of aromatase inhibitors on the 5th and 7th days of life prevented testosterone-induced increase in catecholamine concentrations. The data obtained prove the integration of the processes of testosterone aromatization and catecholamine accumulation in androgen-dependent brain differentiation.

Androstatrienes↗

[Cessation of ovarian cycles in a young mouse while in parabiosis with an older one].

Female mice 3 and 22-24 months of age were jointed in heterochronic parabiosis. That led to permanent estrus in young mice and maintenance of intact anestrus in old mice. After 8-9 weeks of parabiosis there appeared morphological signs of accelerated ageing in the ovaries of young animals, while no changes in the ovaries of old mice were observed. Serum progesterone of young partners decreased to the levels of old animals and estradiol levels remained unchanged, while prolactin content in adenohypophysis was the same as in young single animals but exceeded the level noted in young mice in parabiosis with young partners. Hormone content in old parabionts remained unchanged, as compared to the control. An old organism is thought to be the source of unidentified factors suppressing the ovarian function in young animals.

Aging↗