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We investigated gender-related differences in dynamics of the brain sexual steroids during learning and the decrease of conditioned reflex in the modeling experiment. It was revealed that, before training to conditioned reflexes, females manifested a greater anxiety than males. Significant differences between males and females in formation of the conditioned reflex of passive avoidance were not revealed, whereas the conditioned response decrease were by 2-3 days faster in male rats than in females. It was revealed that there was an increase of testosterone content in various structures of the brain, especially in hippocampus and frontal cortex with its constant level in the blood plasma in learning conditioned response of passive avoidance in male adult rats. Also an increased estradiol concentration was found in females' amygdale, while increased value of estradiol was detected in hippocampus and the singular cortex in decrease of the conditioned response of passive avoidance. In blood plasma, the testosterone level was not changed, and the estradiol concentration was reduced significantly after the decreased conditioned reflex. Different dynamics of changes in the levels of sex steroids in the brain and the blood plasma can indicate a probability of their formation in nervous tissue. The correlation analysis confirms the conception about selective involvement of the brain's testosterone and estradiol in the specific structures in realization ofthe learning and memory processes in adult male and female rats.

The aim of this review is a review of literature data, which characterize participation of monoamines brain systems and sex steroids in regulation (modulation) of the amygdalas' functions. Shown were characteristic noradrenergic, dopaminergic and serotoninergic systems and their representation in amygdala. Effect ofnoradrenaline, dopamine and serotonine on neurons of Amygdala was shown realized from appropriate cell receptors under modulated influence of sex steroids. Combined participation of monoamines and sex steroids occur in regulation of activity in cyclic centre of secretion and releasing of gonadotropins, constituted a base of forming adaptive (sexual, food and aggressive-defensive) behaviour, including stress reaction. The presented data could be used for understanding influence of gender factor on personality characteristics of humans, cognitive abilities and behavioural reactions, and also in application to development of optimal medicinal treatment of psychoneurological diseases.

The purpose of research is the definition of androgens role and myocardial androgen receptors and sex steroids in males under metabolic and hormonal "stress" induced by the experimental diabetes. Research was carried out on 60 rats-males, mass 180,0-200,0 g. The diabetes reproduced by single injection of alloxan (200mg/kg). Androgen receptors were revealed by the radiometric and radioautography methods. The content of glucose, immunoreactive insulin, testosteron, estradiol, corticosteron and somatotropin were defined in animals blood plasma. On the early terms of alloxan diabetes estradiol concentration increase against a background of testosteron decrease which causes the "feminization" of the sexual hormonal balance. On the other side the increase of androgen receptors expression by cardiomyocytes causes the intensification of myocardium tissue physiologic ability to androgens perception positively influencing on the metabolism. Consequently, androgens provoke stimulating effect on the myocard metabolism in males at early stages of the experimental diabetes.

The interaction between prolactin and theophylline as well as between prolactin and guanosine triphosphate during Ca2+ release from intracellular stores of estradiol-treated porcine oocytes isolated from the ovary at the stage of follicular growth were studied using fluorescent Ca(2+)-sensitive probe chlortetracycline. In the absence of estradiol, prolactin or theophylline induced Ca2+ release from intracellular stores; however, no increase in Ca2+ release was observed after their combined action. Conversely, Ca2+ release from intracellular stores increased only after the combined exposure to prolactin and theophylline in the the presence of estradiol. In the absence of estradiol, guanosine triphosphate induced calcium release alone and together with prolactin. Protein kinase C regulated Ca2+ release from intracellular stores after the combined exposure to prolactin and theophylline only in the presence of estradiol; while the activation of protein kinase C required no estradiol during the combined exposure to prolactin and guanosine triphosphate. The data obtained indicate the effect of estradiol on Ca2+ release from intracellular stores after the combined exposure to prolactin and theophylline, while no such effect was observed after the combined exposure to prolactin and guanosine triphosphate.

Individual and combined effects of chorionic gonadotropin (CG), estradiol, and progesterone on the production of IFNgamma and IL-4 by human peripheral blood lymphocytes was studied in vitro together with certain intracellular mechanisms underlying the hormonal effects. High CG dose (100 IU/ml) proved to significantly decrease IFNgamma level in the T cell culture supernatant, although this effect was not observed at the background of steroid hormones. In contrast, progesterone (100 ng/ml) increased IFNgamma production by activated T lymphocytes but proved inefficient in a physiological combination with CG and estradiol. IL-4 production was almost doubled by all studied hormones and their combinations, which considerably decreased the IFNgamma/IL-4 ratio in the culture. Inhibition analysis employing blockers of cAMP-dependent protein kinase (H-89) and L-type calcium channels (verapamil) as well as an antagonist of progesterone nuclear receptors (RU-486) demonstrated that the inhibitory (for IFNgamma) and stimulatory (for IL-4) effects of CG were mediated by cAMP, while the effects of steroid hormones on the production of these cytokines were realized through genomic and non-genomic mechanisms (the latter mechanisms were largely mediated by L-type calcium channel regulation). Overall, the studied reproductive hormones could efficiently regulate synthesis of the main Th1 (IFNgamma) and Th2 (IL-4) cytokines by T lymphocytes and seem to play the key role in changing the pregnancy-specific pattern of secreted cytokines.

Progesterone and oestradiol serum level was investigated in WAG/Rij rats with genetically determined absences. Blood samples were drawn before and after the pregnancy following the parturition. The serum concentration of progesterone increased after the 3rd day of pregnancy. There is no increasing of oestradiol during pregnancy as large as this. The progesterone is kept high to the 18th day of pregnancy and drastically decreased before the parturition. Common duration of absences--spontaneous spikewave discharges (SWD), frequency and the duration of every SWD decreased from 3rd to 19th days of pregnancy before the parturition. On the basis of these data and modern investigations, regulation of GABAA receptor expression during pregnancy by progesterone (Brusaartd A. B. et al., 1999) it can be assumed that the changes in the parameters of SWD are possibly correlated with the progesterone changes in serum during pregnancy in WAG/Rij rats.

The paper provides a comparative analysis of the effects of imbalance of gonadal hormones on behavioral processes in rats of both sex. Learning was assesses in active and passive avoidance paradigms, behavior was evaluated in the "open field" test. Hemigonadectomy in male rats or hemiovariectomy in female rats was found to fail to modify the dynamics of acquisition and reproduction of active avoidance and passive reactions as compared to the controls, but to affect the pattern of animal behavior in the "open field" test. Castration of rats of both sex impaired the acquisition and retention of active avoidance performance. Excess of testosterone in male rats significantly inhibited the ability of the animals to form an active avoidance response. Excessive estradiol levels in female rats accelerated the acquisition of active avoidance performance and greatly attenuated extinction of this performance. Gonadal hormonal treatment did not alter the reproducibility of passive avoidance performance. The lack of estrogens resulted in amnesia of passive avoidance performance while that of androgens failed to destroy passive avoidance performance. Excessive estradiol in female rats or its lack in male rats significantly modified the pattern of animal behavior in the "open field" test. The absence of estrogens or their excess did not affect the behavior of rats with exception of individual components.

Silver fox males were tested for sexual and agonistic behaviour after introduction of a female at different stages of the reproductive cycle. The high level of aggressive interactions between male and female and no mountings were observed out of the reproductive season. During the reproductive season, the introduction of anoestrus female did not affect the aggressive behaviour but increased the number of mountings while introduction of a receptive female reduced aggressive contacts and augmented sexual behaviour in pairs independently of mating. Considerable variations in testosterone and oestradiol but not cortisol plasma levels were observed between different stages of sexual activity. At the beginning of the reproductive season, silver fox males responded to anoestrus females with significant increase in their blood levels of testosterone and oestradiol. Contents of these two hormones did not change in males during the reproductive season when they encountered a receptive female. A female did not elicit any cortisol response in a male during different periods of the reproductive cycle. The data obtained suggest that the sexual behaviour in silver fox males can be facilitated by testosterone and oestradiol while aggressive interactions between male and female occur independently of these hormones.

Examinations of 33 patients with the polycystic ovaries syndrome with measurements of monoamines, ovarian and gonadotropic hormones, and prolactin revealed disordered monoaminergic regulation in all the patients, manifesting by reduced dopamine level in normoprolactinemia and its reduction parallelled by increase of serotonin level in hyperprolactinemia. Disturbances in monoaminergic regulation result in increased level of LH and reduction of FSH levels in all the patients, as well as different prolactin levels. Hyperandrogenism in patients with the polycystic ovaries syndrome and normoprolactinemia is determined by a unidirectional increase of testosterone and androstenedione, whereas in hyperprolactinemia a sharp increase of testosterone content occurs in parallel with decrease of androstenedione level. Normal total estradiol level was associated in all the examinees with manifest relative hypoestrogenism. The detected disorders in hormonal-mediator relationships in patients with the polycystic ovaries syndrome give us new information on the pathogenesis of this condition, which may be important for its diagnosis and treatment.

Histological, electron microscopic and histoautoradiographic methods were used to study structural and neurochemical features of the development of neurons of the hypothalamic paraventricular nuclei (PVN) and the medullary nucleus of the solitary tract (NST), which had been grafted from 20-day-old rat fetuses into the anterior eye chamber of ovariectomized female rats not exposed (control group) and exposed (experimental group) to prolonged estrogen action (during 4 weeks). The exposure to estrogen stimulated the growth, cell differentiation, RNA transcription and synaptogenesis in the grafted PVN and NST neurons. The data obtained seem to provide additional evidence that PVN and NST neurons belong to sex-dependent brain neurons.

The influence of estradiol (E2) was studied on the production of type III procollagen by cultivated fibroblasts from the skin of healthy donors and SSD patients. It has been found that when in the norm E2 (concentration 10(-8) and 10(-7) M) inhibits the production of type III procollagen. In SSD the hormone's effect is not found. Here the quantity of E2 receptors in cells from SSD patients is 1.96 time lower than the norm. The resulted data testify to the fact that the decrease of E2 receptors in fibroblasts from SSD patients may be one of the factors contributing to the increase in the functional activity of cells and to the fibrosis progression.

A study was made of the effect of ovariectomy and administration of estradiol-dipropionate on the level of estrogen receptors, low molecular protein fractions, incorporating fatty acid binding proteins (FABP), and free fatty acids (FFA) in the protein fractions of the cytosol of the intestinal mucosa of mature and immature female rabbits. The female rabbit upper intestinal mucosa was shown to possess cytoplasmic estrogen receptors and to have low metabolic activity of estradiol dehydrogenase (not being target tissue). Ovariectomy caused a decrease in the level of estrogen receptors, protein fractions, incorporating FABP, and FFA in them in enterocyte mucosa cytosol as compared to respective parameters in female rabbits in the pubertal and mature periods of their development. Estrogens were involved in the regulation of the level of intestinal fatty acid binding protein fractions and in ensuring physiological concentrations of absorbed fatty acids.

The relationships between gonadal and glucocorticoid hormones and reproductive behaviour were estimated in two groups of silver fox males classified as either low or high sex activity. Levels of testosterone and cortisol in peripheral plasma measured by radioimmunoassay did not differ between the groups. However, when receptive females were introduced to experimental males, levels of testosterone in plasma increased significantly only in the males with high sex activity within 1 hr after a test of sexual behaviour. Low sex activity of silver fox males correlated with an increased level of aggressive behaviour and decreased fertility.

Patients with the uninhibited urinary bladder of the hyperreflexia type and the vesicoureteral reflux were subjected to multimodality examinations which included excretory urography, retrograde cystometry, cystography, profilometry of the ureterovesical anastomosis, cytologic investigation of estrogenic saturation, determination of the concentration of follicle-stimulating hormone of the pituitary and estradiol by means of radioimmunoassay. As many as 56 girls aged 4 to 15 years underwent examination. It has been demonstrated that dysfunction of the urinary bladder of the hyperreflexia type is of crucial role as an active mechanism of extra-vesicalization of the intra-vesical part of the ureter, associated with its antireflux function distress.

The peculiarities of physical growth and sexual maturity were investigated in 300 girls with accelerated physical development aged 9 to 17 years. It was found, that maximum rates of the somatic formation, a high level of the growth hormone and testosterone as well as low estradiol secretion are seen during the prepubescent stage of maturity. After the menarche the somatic formation rates, the growth hormone and testosterone secretion decrease, whereas estradiol secretion progressively rises.

Gel electrophoresis was used in a comparative study of prolactin content in the hypophysis of rats of different age and sex, and at various stages of the estral cycle. The hormone level in the pubertal rats was twice or thrice greater than in the immature ones; it was by 16% less at the diestrus than at the estrus stage. There was no change in the hypophysis prolactin content in male rats at puberty. Ovariectomy was accompained by a sharp reduction of prolactin in the hypophysis. Replacing estradiol therapy increased the amount of prolactin in the hypophysis, without bringing it, however, to the level characteristic of intact rats. Estrogens are responsible for the maintenance of prolactin level, but apparently other factors influencing its content in the hypophysis also exist.

Estradiol (10(-7)-2 . 10(-5)M) is shown to inhibit the activity of phosphodiesterase of the soluble fraction of the mature rat womb tissue and to have no effect on the activity of adenylate cyclase of this tissue membrane fraction and on the phosphodiesterase of the tissue of the brain, heart and outer segments of the rod-cell. When blocking the estradiol cytosol receptors by clomiphene there is no inhibitory effect of the hormone on the activity of phosphodiesterase of the womb tissue preparations. Specific binding of estradiol by the cytosol receptors increases in the presence of guanylic nucleotides (10(-5)-10(-4)M); ATP does not affect this process. In the presence of guanyl-5-ilimidodiphosphate (Gpp(NH)p), a nonhydrolyzed analog of GTP, clomiphene does not block receptor binding of estradiol. ATP and GTP (10(-6)-10(-5)M), contrary to Gpp (NH)p, inhibit the phosphodiesterase activity. Independent of their effect on the enzymic activity, all the studied nucleotides partially or completely eliminate the inhibitory effect of estradiol on phosphodiesterase.

In adult rats estradiol was found to enhance functional activity of mast cells, whereas progesterone inhibited substantially this effect. The experiments with denervated uterus revealed that the stimulating estrogen effect on mast cells in its tissues was in part associated with activated neuromediation induced by these hormones.

A study was made of the content in human milk of hormones which regulate together with their specific function processes of protein assimilation and synthesis. These hormones (thyroxine, triiodothyronine, 17 beta-estradiol, prolactin, 11-hydroxycorticosteroids) were determined in the first days of lactation, in the most important period in the nutrition of a newborn and in the formation of lactation. Chromatography, radioimmunoassay and fluorometry were used. The aim of the study was to determine the levels of exogenous hormones which influence the metabolism of proteins received by a newborn. During the first 10 days of lactation the content of prolactin in human milk was 154.5-546.0 muunits/ml, that of 17 beta-estradiol 34.2-124.4 pg/ml, that of thyroxine 0.5-1.1 micrograms%, that of triiodothyronine 8.6-20.8 ng%. A possible involvement of milk hormones in the regulation of anabolic processes of a newborn as well as changes in the first 3-6 days of lactation of the prolactin and 17 beta-estradiol content in milk in connection with the regulation of the start of lactation are discussed.

Cloning of DNA and complementary mRNA of bovine, rat and human proopiomelanocortin (POMC) was carried out. A structural analysis of the cloned cDNA of POMC was performed. Using restriction fragments of bovine, rat and human POMC cloned cDNA, probes for molecular hybridization based on one-chain bacteriophage M13 were made. Using the dot-hybridization technique with labeled [32P] POMC cDNA, the effect of 17 beta-estradiol and adrenalectomy on the POMC mRNA level in rat hypophysis was studied. The hormone was shown to significantly decrease the POMC mRNA content at a concentration of 4 and 8 micrograms per 100 g of body weight 4 hours after injection. Adrenalectomy caused a 2-3-fold increase in the POMC mRNA level in rat hypophysis after a period of 5-7 days. The possibility of polyhormonal control of POMC genome transcription is discussed.

A study was made of reception of 17 beta-estradiol, progesterone, and testosterone in human endometrium during pregnancy. In the cytozol of the endometrium each of the sex steroids was bound by three different receptor components, two of which were represented by highly specific proteins. The maximal capacity of specific cytozol receptors to each of the sex steroids was measured in normal and pathological pregnancy; in the latter case the number of receptors to progesterone proved to be decreased. It is supposed that one of the specific binding components is necessary only under conditions of increased functional load upon the organ.

The administration of methiamide, a blocker of histamine H2-receptors, to rats was shown to prevent the induction of hexokinase (HK) and glucose-6-phosphate dehydrogenase (G-6PD) caused by both histamine and estradiol. An inhibitory effect of methiamide remained stable up to 16 h after histamine and estradiol administration. Diphenhydramine, a blocker of histamine H1-receptors, produces a short-term inhibitory effect on the HK and G-6PD activity stimulated by histamine and estradiol. The short-term nature of the diphenhydramine effect may be attributed to a low affinity to histamine H2-receptors and histamine fast dissociation. It may be concluded that some of the estradiol effects, particularly the HK and G-6PD induction in the uterus are histamine-mediated, apparently by means of H2-receptors. The administration of histamine to rats increases the uterus mass causing its inundation, and H1- and H2-blockers prevent this effect of histamine. However, the above histamine antagonists do not inhibit uterus inundation caused by estradiol. A conclusion is made that estradiol stimulates the uterus inundation not only by means of histamine but also by some other means.

The author presents the results obtained at the Laboratory of Hormone Biological Standardization, Institute of Experimental Endocrinology and Chemistry of Hormones, AMS USSR. The combination of adenohypophyseal cell cultivation with radioimmunoassay to determine hypophyseal hormones and the technique of labeled precursors provided an opportunity to definea group of regulators influencing the adenohypophysis directly, and to isolate it from biologically active factors, a hypophyseotropic effect of which is mediated by the hypothalamus. It has been shown that some secretogenes can play the role of the regulators of cell division in the adenohypophysis. The effects of the hormonal regulators on the proliferation and differentiation of hypophyseocytes are made both directly and indirectly. The diversity of regulatory effects on some hypophyseal functions is emphasized; it results in the recognition of heterogeneity of some endocrinopathies previously regarded as belonging to the same nosological entities.

The effect of estradiol on DNA synthesis in hepatocytes was investigated for a study of the functional importance and mechanism of action of sex steroids in the liver. After administration of 17, beta-estradiol dipropionate at a dose of 20 micrograms per 100 g of body mass to ovariectomized albino female rats for 11 days the kinetics of incorporation of 3H-thymidine triphosphate in liver cell nuclei and chromatin was determined. A stimulating effect of the hormone on the tracer incorporation in the nuclei and chromatin was established. A similar tendency was noted in immature female rats. The tracer incorporation depends on the cytosol presence in the system. The rate of incorporation has been shown to increase under the influence of the liver cytosol of intact rats. In can be assumed that estradiol is involved in the regulation of liver DNA synthesis raising matrix activity and modulating cytosol factor activity.

Experiments were conducted on rats; it was shown that insulin, adrenaline, hydrocortisone, somatotropin, estradioldipropionate, deoxycorticosteroneacetate caused a rise of the membrane potential of individual muscle fibers, hepatocytes, motor neurons of the spinal cord, critical depolarization threshold, membrane resistance, shifts, in the K+, Na+ content. Simultaneously with these changes of the electrical properties of the membrane there occurred a rise of the RNA fraction synthesis, transcribing capacity of chromatin. Inhibitors of protein biosynthesis (actinomycin D, olivomycin, X-irradiation) prevented the hyperpolarization development and activation of genetic apparatus, whereas energy metabolsim inhibitors (sodium fluoride, monoiodine acetate, 2,4-dinitrophenol) failed to influence the rise of the membrane potential caused by hormones. Shifts in the electrical properties of cell membranes caused by hormones are connected with the genetic apparatus activation.

The content of receptors to estradiol and testosterone was determined in cytoplasmic and nuclear fractions of hypothalamus and brain cortex of male rats in the early postnatal period. Receptors to both estradiol and testosterone were revealed in cytosol and nuclear fractions, with the decrease in their concentration observed from days 1 to 5. The data obtained demonstrate that receptors to sexual hormones take part in the brain differentiation and regulation of hypophysis gonadotropic function by male or female type.

The effect of verapamil, the blocker of calcium channels, on estradiol modulation of the LH-RH effect on the secretion of the luteinizing hormone was studied in experiments on ovariectomized rats. It was shown that verapamil influenced neither the basal nor the LH-RH activated secretion of the hormone from the pituitary gland. However verapamil inhibited the effect of estradiol increasing the secretory response to LH-RH. Hence, the modulating effect of estradiol on the secretion of the luteinizing hormone depended on the transport of extracellular calcium into hypophyseal cells.

A single total body cooling was found to cause a more distinct alteration in carbohydrate metabolism in lung tissue of male rats as compared with female rats. These metabolic alterations were less distinct in castrated males. Preadministration of one of the sex hormones (testosterone, estradiol or progesterone) into the castrated males led to normalisation of carbohydrate metabolism in cooling; among the sex steroids estrogen was the most effective.

Effect of estradiol propionate on activity of seven enzymes from rabbit uterus was studied. Simultaneously with the known estrogen-induced enzymes, activity of some other enzymes from uterus cells (tyrosine transaminase, acetylcholinesterase, butyrylcholinesterase) was also studied. The hormone induced all the enzymes studied except of butyrylcholinesterase. After induction with the estrogen a new isoenzyme fraction was found in peroxidase: at the same time, content of isoenzymes of lactate dehydrogenase, tyrosine transaminase and acetylcholinesterase was increased.

The effect of estradiol and progesterone on the activity of 3 regulatory enzymes of glycolysis (hexokinase, phosphofructokinase and pyruvate kinase) in the brain of female rats was studied in the initial phase of hormonal action. Steroids were capable of modifying epileptic activity caused by pentetrazol, the action of estradiol being epileptogenic, that of progesterone anticonvulsant. Hormone action modifying epileptic activity, probably results from changes in intracellular metabolism and from changes in electrogenesis of nerve cells, the second mechanism being predominant.