Search PubMed⌕ Search

Biomedical subjects

N D Nosenko

Publications and source records attributed to N D Nosenko.

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↗

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↗

[The perinatal stress modification of the reactivity of the hypothalamo-hypophyseal-adrenal system].

The literature data and the results of authors research work concerning long-term effects of prenatal stress and of early postnatal handling on the hypothalamic-pituitary-adrenal stress response are reviewed in the article. Functional state of that system, and the role of hormones, biogenic monoamines and glucocorticoid receptors of the brain in pathogenesis of its alteration are discussed. Special reference is made to gender- and age-related effects of pre- and postnatal stress. The body of evidences supports basic states of the brain hormone-neurotransmitter imprinting during early ontogenesis.

Acute Disease↗

[Physical endurance in rats exposed prenatally to stress of exogenous glucocorticoids].

Gender- and age-related peculiarities of the influence of prenatal stress or exogenous glucocorticoids on physical endurance in rats were found in the experiments using fatigue test. Normal adult females were of greater endurance than males. Prenatal stress resulted in increased physical fatigue mainly in females while sexual differences were reversed. Hydrocortisone acetate administration to pregnant rats prevented sexual dimorphism in physical fatigue development in adult animals due to increase of physical endurance in males and its decrease in females. In aging rats disappearance of both sexual differences and prenatal stress effects took place against a background of fast physical fatigue development.

Age Factors↗

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 sexual dimorphism of the monoaminergic system of the brain: the effects of prenatal stress and neonatal androgenization in rats].

Prenatal stress and neonatal androgenization manifest themselves by early postnatal changes in sexual differences of catecholamine and indoleamine contents and turnover in the preoptic area and mediobasal hypothalamus in 10-day-old rats. Neonatal androgenization did not prevent the formation of sexual dimorphism of noradrenaline content and turnover in the preoptic area but enhanced sexual differences of dopamine turnover in both these brain areas.

Animals↗

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↗

Influence of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced injury of dopaminergic nigrostriatal system on movement components of the instrumental reflex and motor thalamic neurons' reactions in the cat.

Peculiarities of excitation and inhibition in ventral lateral and ventral anterior thalamic neurons were studied in cats with movement disorders (bradykinesia and muscle rigidity) induced by injury of nigrostriatal dopaminergic neurons with neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (5 mg/kg daily, intramuscularly for five days). As was shown in chronic experiments, mean discharge frequency of neurons related to initiation of upper limb movements increased. Excitation of these neurons coincided with movement initiation, flexion and extension becoming more prominent and prolonged as compared with normal animals. In parallel to those changes, bradykinesia developed. In acute experiments performed under ketalar anaesthesia and myorelaxine immobilization it was found that neurotoxin caused a decrease of the inhibition duration and effectiveness in relay and non-relay thalamic motor nuclei neurons. The inhibition deficiency was accompanied by a shortening of latencies of orthodromic responses evoked by red nucleus stimulation. Two days after the last neurotoxin injection, light microscope examination revealed that about 48% of neurons located in the pars compacta of substantia nigra were destroyed. Electron microscopic analysis showed hydropic changes in perykaria and dendrites in most neurons of the substantia nigra pars compacta that are typical of the light type of degeneration. Pathomorphological processes in the synaptic apparatus were also found. The content of dopamine in the caudate nucleus fell to 30% as compared with intact animals. The suggestion is made that the deficiency of inhibition developed in motor thalamic neurons in response to nigrostriatal system destruction results from attenuation of dopamine-modulated direct GABAergic nigrothalamic influences and/or might be connected with increased inhibition of inhibitory interneurons of the same thalamic nuclei conditioned by pallidum disinhibition.

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↗

[Excitation and inhibition processes in the neurons of the thalamic motor nuclei of normal cats and following an N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced lesion of the nigrostriatal dopaminergic system].

Peculiarities of excitation and inhibition evoked in motor thalamic nuclei (VA-VL) neurons by electrical stimulation of red nucleus were studied on intact cats and after injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 5 mg/kg i.m., p.d. during five days). Two days after the last injection as much as 48% of nigral neurons were destroyed and the content of dopamine in the caudate nucleus fell to 30% as compared to intact animals. Before acute experiments all cats were anaesthetized with ketalar and immobilized with myorelaxine. It was found that MPTP injections caused a decrease of the inhibition duration and effectiveness in relay and nonrelay VA-VL neurons. The inhibition deficiency was accompanied by shortening of latencies of orthodromic responses evoked by red nucleus stimulation and facilitation of antidromic spikes invasion into somata of relay neurons after motor cortex stimulation. It was suggested that the reduction of GABAergic nigro-thalamic influences modulated by dopamine underlay the developing deficiency of inhibition.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

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↗

It is possible that noradrenaline is the biogenic monoamine responsible for androgen-dependent sexual brain differentiation.

The effect of neonatal testosterone propionate (TP) treatment and its combination with alpha-methyl-p-tyrosine (alpha MPT) on noradrenaline, dopamine and serotonin contents in the hypothalamus of 7-day-old female rats has been studied. The property of alpha MPT to prevent anovulatory sterility in neonatally androgenized rats earlier established by the authors is related to interfering with a rise of hypothalamic level of noradrenaline induced by TP in the early postnatal period. The experimental data give evidence against the participation of dopamine in sexual differentiation of the brain and indicate the secondary character of serotonin content changes in the hypothalamus in relation to the noradrenaline level. Hence, noradrenaline may participate in androgen-dependent sexual differentiation of the hypothalamus.

Androgens↗

New evidences for participation of biogenic monoamines in androgen-dependent sexual differentiation of hypothalamic control of gonadotropin secretion in rats.

Corpora lutea have been found in the ovarian tissue transplanted into the anterior ocular chamber of castrated two-month-old male rats receiving on 3rd through 7th post-natal days alpha-methyl-p-tyrosine or p-chlorophenylalanine. Administration of these agents in combination with testosterone propionate to newborn female rats prevented essentially development of the anovulatory syndrome and maintained a normal picture of vaginal smears, ovarian and uterine structure as well as cyclic changes of adenohypophyseal and blood plasma lutropin contents and normal levels of estradiol and progesterone in the blood plasma except of progesterone level in animals receiving alpha-methyl-p-tyrosine. The preventive effect of the adrenoblocking agents droperidol and propranolol was weak and inconstant. Results suggest participation of catecholamines and serotonin in the androgen-dependent sexual differentiation of the brain in rats.

Animals↗

[Effect of neonatal androgenization on biogenic monoamines of the hypothalamus and the functional activity of the rat pituitary].

Injection of testosterone-propionate to female Wistar rats on the 2nd--4th days of birth failed to alter the serotonin level, but produced a sharp fall of the noradrenaline and dopamine levels in the hypothalamus of 3 1/2-month-old animals. This was accompanied by an increase in the prolactin content in the adenohypophysis with the retention of the normal somatotropic activity. The results of these studied indicated the participation of catecholamines in the pathogenesis of the anovular sterility, and elucidated current views on the control of the hypophysial gonadotropic function.

Animals↗