[Estrogen receptors in the diagnosis and treatment of hormone-dependent tumors].

The paper presents the current data available on the etiology of tumor diseases, among other things, shows the role of hormones, namely: estrogens and their receptors, in the mechanism responsible for the occurrence of these diseases. Each tumor was shown to have its receptor status and to be unresponsive to this or that therapy differently. The efficiency of treatment and its prognosis may be determined if the receptor composition of an involved organ is estimated correctly. The authors summarize the data available in the literature, as well as the results of their own investigations explaining the selective effect of estradiol receptor agonists and antagonists in various tissues. The mRNA varieties that potentially encoding for the synthesis of different subtypes of estrogen receptors (ER) - ER-α and ERß, which are also coded by various genes located in different chromosomes. Pituitary adenomas as hormone-dependent masses are described in detail. The authors data on the concentration of nuclear estrogen receptors in different types of adenomas are given.

[Receptor mechanisms of action of sex hormones. Can the receptor work without a ligand?]

Among endocrinologists, it is generally accepted that most of the effects of steroid hormones are transmitted to the cell through their receptors located on intracellular sites, mainly on the nuclei of cells, and these mechanisms are intensively studied. A lot of information has been accumulated about the specific function of each hormone, changes of which were observed after removal of the gland and its hormonal compensation. The basis of the position of endocrinologists in this situation is the fact that the removal of the gland eliminates many physiological and behavioral responses depending on the secretory function in this gland. To restore a specific response, replacement therapy with the appropriate hormone is necessary. However, researchers are at a standstill when neurotransmitter or growth factors, acting through their own membrane receptors, are able to replace the effects of steroid hormones and activate steroid receptors through secondary messengers, even in the absence of steroid hormones.

[The influence of estrogens on the central nervous system].

The article is dedicated to the influence of sex hormones, especially estrogens, on the central nervous system. The author summarizes literature data and the results of his own research into the mechanism of estrogen action, both via cell receptors and neuromediator systems. The latter include cholinergic, catecholaminergic, and serotonergic systems of various brain structures, such as the hypothalamus, hippocamp, forebrain, substantia nigra etc. The article demonstrates differences between the action of estrogens in male and female subjects, both under physiological conditions and in cases of psychopathological disorders (depression, more often observed in women, and aggressive and anti-social behavior, more typical of men). The data presented in the article demonstrate the scope of the influence of sex hormones on various systemic reactions, such as mood, mental ability display, and sexual behavior. The data on neuroprotector estrogen effects and the discovery of estrogen-independent synaptogenesis in the hypothalamus and hippocamp are related with postmenopausal changes in the brain functioning. Postmenopausal therapy with estrogens may be effective in protection against Alzheimer disease.

[Neuroendocrine effect of sex hormones].

The paper provides a generalization of data and the results of own experiments on influence ovarian steroids on the hypothalamus and other brain areas related to reproduction. Ovarian hormones have widespread effects throughout the brain: on catecholaminergic neurons and serotonergic pathways and the basal forebrain cholinergic system, as well as the hipocampus, spinal cord, nigrostriatal and mesolimbic system, in addition to glial cells and blood-brain barrier. The widespread influences of these various neuronal systems ovarian steroids have measurable effects on mood and affect as well as on cognition, with implications for dementia. There are developmentally programmed sex differenced in hippocampal structure that may help to explain differences in the strategies which male and female rats use to solve spatial navigation problems. The multiple sites and mechanisms of estrogen action in brain underlie a variety of importants effects on cognitive and other brain functions--coordination of movement, pain, affective state, as well as possible protection in Alzheimer's disease. Estrogen withdrawal after natural or surgical menopause can lead to a host of changes in brain function and behavior.

[Developmental stages of the Endocrinology Research Centre of the Russian Academy of Medical Sciences].

The article is devoted to the history of the development of the Endocrinology Research Centre.

[Physiological importance of numerous sex hormone receptors].

Numerous effects of sex hormones on the brain are mediated by interaction with intracellular steroid hormone receptors acting as regulators of transcription. These are the classical receptors ERalpha, ERbeta and ERgamma. Some estrogenic effects cannot be attributed to ERalpha or ERbeta, this suggests the existens of additional receptor subtypes. Rapid effects of estrogen could be explained by the presence of plasma membrane-associated ERs, that may be coupled to downstrem signal transduction pathways typically associated with rapid activation by growth factors and neurotransmitters. Both nuclear and plasma-membrane-associated ERs probably originate from the same gene and transcript that produce ERalpha and ERbeta.

Influence of serotonin on the development and migration of gonadotropin-releasing hormone neurones in rat foetuses.

This study used a pharmacological approach to evaluate the consequences of the metabolic perturbations of neurotransmitters on brain development. Pregnant rats received p-chlorophenylalanine (pCPA), an inhibitor of serotonin (5-hydroxytryptamine, 5-HT) synthesis, or saline (control) from the 11th day of gestation once or daily up to the 15th, 17th and 20th day, followed by processing of the forebrain and/or nasal cranium of foetal males and females for high-performance liquid chromatography of monoamines, radioimmunoassay of gonadotropin-releasing hormone (GnRH) and quantitative and semiquantitative immunocytochemistry for GnRH. The pCPA treatment resulted in a 50-70% depletion of 5-HT in the nasal crania and forebrains at any studied age. Radioimmunoassay showed no change in GnRH content in 5-HT deficient foetuses at E16 compared to controls, being higher in both cases in the rostral forebrain than in the hypothalamus. In controls at E21, the GnRH content in the hypothalamus exceeded that in the rostral forebrain, whereas in the 5-HT deficient group the opposite was found. These data suggest that 5-HT provided a stimulating effect on GnRH neurone migration, and this was confirmed by quantification of GnRH-immunoreactive neurones in the forebrain along the trajectory of their migration. At E18 and E21, the fractions of GnRH neurones in the rostral part of the trajectory in pCPA-treated foetuses were greater than those in control foetuses but the opposite was true for the caudal part of the trajectory. Moreover, 5-HT appeared to control the proliferation of the precursor cells of GnRH neurones and their differentiation, as derived from the observations of the increased number of GnRH neurones in the forebrain of foetuses of both sexes, as well as the region-specific decreased neuronal size and content of GnRH in 5-HT-deficient females. Thus, 5-HT appears to contribute to the regulation of the origin, differentiation and migration of GnRH neurones.

Role of sex hormones in development of pituitary adenoma.

Role of sex hormones in the development of pituitary adenomas was investigated by analyzing the content of nuclear estradiol and testosterone receptors in different tumors of the anterior pituitary: prolactinomas, meningiomas, growth hormone-producing adenomas, astrocytomas, neurinomas, and ependymomas. The concentration of nuclear estrogen and androgen receptors in prolactin-secreting pituitary adenomas was much higher than in growth hormone-producing adenomas and other pituitary tumors.

[The functional activity of the ATP-dependent K+ channels of normal pancreatic beta cells and in pathology]. / Funktsional'naia aktivnost' AFT-zavisimykh K+ kanalov beta-kletok podzhelludochnoi zhelezy v norme i pri patologii.

The paper deals with the analysis of the status of ATP-dependent K+ channels of pancreatic beta cell functional by attenuated under the effect of streptozotocin and simultaneous assessment of their reaction to sulfonylamide agents glybenclamide, glipizil and glyclazid. Highly specific response of the tested ionic channels showed under the effect of both glucose and sulfonylurea agents. Analysis of the time course of electrophysiological processes coursing in them, showed appreciable changes in the time of the channel closing, which led to deceleration of insulin secretin starting from the moment of exposure to glucose or sulfonylurea agents till exocytosis of insulin quantum. Glybenclamide proved to be the most active of the tested agents as regards their secretogenic properties.

[Relationship between regulatory effects of serotonin and testosterone on the development of the LHRH producing system of the rat brain during the prenatal period of development]. / Vzaimosviaz' reguliatornykh vliianii serotonina i testosterona na razvitie liuliberinprodutsiruiushchei sistemy mozga u krys v prenatal'nom periode razvitiia.

We have performed radioimmunoassay of LHRH in rostral and septal-preoptic brain regions, as well as in mediobasal hypothalamus of male and female fetuses at day 21 of the prenatal period after the injection to pregnant females on days 11-20 of gestation of either p-chlorophenylalanine (PCPA) or of a combination of PCPA with ethane-1,2-dimethane sulfonate (EDS). Control animals received the injection of the same volume of physiological saline. In the control fetuses, both males and females, the level of LHRH in the rostral brain region was significantly lower than in the septal-preoptic region. The administration of PCPA increased the level of LHRH in the rostral brain region and decrease it in the septal-preoptic region, the effect being more prominent in males. When EDS was administered on the background of PCPA administration, sex-related differences in the level of LHRH in the studied brain regions were no longer present. It is proposed that serotonin stimulates migration of LHRH neurons in rostral-caudal direction, and this effect of serotonin is more significant in males, since it is potentiated by testosterone.

Neuroendocrine control of the gonadotropic function of the hypophysis in experimental diabetes.

The stability of the function of the reproductive system depends on a multitude of factors of the internal and external milieux. Serious disturbances in its function, with alterations in carbohydrate homeostasis, underlie such diseases as diabetes mellitus. Disturbances to the functional activity of the reproductive system in laboratory animals with diabetes are known to be associated not only with destructive changes in the gonads, but also with dysfunction of the hypothalamo-hypophyseal complex [9, 11]. Published data show that these lesions have different severities in male and female individuals [7, 8]. The question of the extent to which lesions due to the diabetic state depend on the level of sex steroids and insulin in the body thus far remains unanswered. Unlike the situation in males, females are characterized by cyclic changes in the activity of the reproductive system. Thus, it is possible that differences in the regulation of gonadotropic function in male and female rats, observed in normal animals, could explain their different sensitivities to diabetes. Thus, we elected to carry out various studies of the functional activity of the hypothalamo-hypophyseal-gonadal system in male and female rats with experimental diabetes induced by administration of streptozotocin (STZ).

[The neuroendocrine regulation of gonadotropin and prolactin secretion and the role of neuromediators]. / Neiroéndokrinnaia reguliatsiia sekretsii gonadotropinov i prolaktina i rol' neromediatorov v nei.

The paper deals with the neuroendocrine relationships between true neuromediators of adrenergic and cholinergic nature as well as the neuromediators of peptidic character and the neurosecretory neurons controlling the secretion of gonadotropines and prolactine. The properties of about 30 neuromediators of different character with consideration for the structures of the central nervous system, participation in the synthesis and secretion of gonadoliberine, gonadotropines and prolactine and hence functioning of the reproductive system as a whole are characterized. The significance of the hormonal background of sexual steroids in the system of these complex relationships is analyzed. The author's and literature findings on the time-course of changing the contents of catecholamines in the hypothalamic structures relating to the control of the gonadotropic function of pituitary body are studied; the correlation relationships between a changed level of sexual steroids and gonadotropines in the blood during the cycle and the time-course of changing the catecholamines and luliberine in the hypothalamus are discussed. The possible mechanisms of coordinating the different neuromediators of adrenergic character and amino neuromediators with various mechanisms of action in the regulation of normal activity of the reproductive system are investigated.

[Characterization of pancreatic beta cell receptors binding sulfanilamide drugs]. / Kharakteristika retsteptorov beta-kletok podzheludochnoi zhelezy, sviazyvaiushchikh sul'fanilamidnye preparaty.

Analysis of pancreatic beta-cell receptors binding the sulfanilamide drugs widely used in therapy of type II diabetes, such as glibenclamide, glipizide, and gliclazide, showed that these drugs are characterized by excellent parameters of specific binding to these receptors. The receptors were tested for two parameters: number of binding sites and dissociation constant. Glibenclamide was the most active of the drugs we tested, the other two agents being less active. Binding of these agents was reversible. The problem of identification of the examined receptors of sulfanilamides with K(+)-ATP-sensitive channels, similarly active conductors of the information transported by the sulfanilamide drugs in the mechanism of insulin secretion, is discussed.

[Development of the reproductive system in the progeny of rats with streptozotocin diabetes]. / Stanovlenie reproduktivnoi sistemy u potomstva krys, bol'nykh streptozototsinovym diabetom.

Specificities of functioning and development of the reproductive system and mechanism of its regulation with hypothalamic structures were studied in the progeny of rats with streptozotocin diabetes. For this purpose pituitary sensitivity was analyzed in mature animals, as was functional capacity of the feedback system mediating the hypothalamic regulation of gonadotropin secretion in rat males and females at the age when this system normally starts functioning in health. The hypothalamo-hypophyseo-gonadal system feedback mechanism was found to develop in the progeny of female rats with streptozotocin diabetes later than in health. Pituitary sensitivity to LH-RH was reduced and LH level reduced by 1.5 times in mature progeny of rats with streptozotocin diabetes as compared to that in the progeny of healthy rats. These results permit a conclusion that the progeny of rats with streptozotocin diabetes develop disorders in the mechanism regulating the reproductive system of the body, though not so grave as to make this system functioning impossible.