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.

Luteinizing hormone-releasing hormone in thymus and hypothalamus of rat fetuses: suppressing effect of antagonist and of antibodies on concanavalin A-induced proliferation of thymocytes.

The effect of endogenous luteinizing hormone-releasing hormone (LHRH) on the proliferation induced by concanavalin A (Con A) in rat fetal thymocytes was studied. A selective antagonist (2 microg per fetus) or antibodies to LHRH (20 microl per fetus) were injected in utero into 20-day-old rat fetuses, and this resulted in a two- or fivefold decrease in the Con A-induced proliferation of thymocytes, respectively. In combined culture of the antagonist (10-5-10-6 M) with fetal thymocytes, the proliferative response was not decreased. The concentration of LHRH was determined by radioimmunoassay in tissues of immunocompetent organs and in blood serum of 18- and 21-day-old fetuses, and the hormone was found in the hypothalamus, thymus, and peripheral blood. The initially low level of LHRH in the thymus increased by 65 and 40%, respectively, on the first day after birth and became similar to the level in the hypothalamus. In the fetal blood serum, the LHRH level was significantly higher than in the thymus and hypothalamus of fetuses of the same age. The hormone concentration was greatest in the 18-day-old fetuses, and it decreased twofold by the 21st day. The findings indicate that LHRH is involved in regulation of T-cell immunity even during prenatal ontogenesis.

[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).

[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.

[Development of hypothalamic regulation of gonadotropic function of the pituitary in hypoinsulinemic rats]. / Formirovanie gipotalamicheskoi reguliatsii gonadotropnoi funktsii gipofiza v usloviiakh gipoinsulinemii u krys.

Effects of temporary hypoinsulinemia induced by streptozotocin in neonatal age on the development of the mechanism of hypothalamic regulation of hypophyseal gonadotropic function in rats were studied. With this aim the authors analyzed the status and functional capacity of feedback system mediating hypothalamic regulation of gonadotropin secretion in female and male rats at the age when this system starts functioning in health. Streptozotocin injection in the neonatal age induced a reduction of estradiol concentration and of estradiol and progesterone-stimulated preovulatory peak of luteinizing hormone (LH) in 28-day-old females and a reduction of LH concentration in 28-day-old castrated males. Reduced estradiol and LH peak were observed in adult females injected streptozotocin during the first week of life and reduced LH level in adult males. These results permit a hypothesis that streptozotocin administration to rats in the neonatal age disturbed the mechanism of hypophyseal gonadotropic function regulation in mature rats.

[Effects of endogenous opioids on the development of reproductive function in rats]. / Vliianie éndogennykh opioidov na stanovlenie reproduktivnoi funktsii krys.

The influence of opioid peptide on the process of formation of reproductive function in rats was studied. Administration of beta-endorphin to neonatal female rats did not affect the concentrations of oestrogen and androgen receptors in the hypothalamus and pituitary, whereas the content of testosterone receptors was significantly higher in both hypothalamus and pituitary. Chronic administration of beta-endorphin to both female and male rats does not affect the concentration of sex hormones. The results obtained indicate that chronic administration of beta-endorphin to neonatal female rats lead to formation of instable contacts in the mechanism of regulation of hypophysis gonadotropic function.

The effect of neonatal castration of male rats on the level of sex-hormone receptors in the hypothalamus and hypophysis of adult animals.

The concentration of oestradiol (E2) and testosterone (T) cytosolic and nuclear receptors was studied in the pituitary and hypothalamus of adult male rats gonadectomized either on the first day after birth (long-term castrates) or in adulthood (short-term castrates). Intact male rats and short-term castrates had the same levels as each other of cytosolic and nuclear oestrogen and androgen receptors in the pituitary, mediobasal hypothalamus (MBH), and preoptic anterior hypothalamus (POAH). In neonatally castrated males the number of nuclear T-binding sites in the pituitary and both areas of the hypothalamus decreased, whereas the number of nuclear E2-receptors was reduced only in the MBH. The number of E2-receptors in the POAH of such animals increased. The number of E2- and T-binding sites in the nuclear fraction of the MBH and POAH was the same in long-term castrates whether they did not receive testosterone propionate (TP) or received it from 7 days after birth until sexual maturity. Conversely, the T-receptor concentration in the hypophysis of neonatally castrated males who received TP was higher than in such animals which did not, but still lower than the level in intact adult rats; the number of hypophyseal nuclear E2-binding sites in long-term castrates which received TP was 1.5 times higher than in all the other groups of animals. The data demonstrate that in male rats sex-hormone receptors are involved in the sexual differentiation of the brain.

[Effect of alcohol on the content of sex steroid receptors in the hypothalamus and hypophysis of male rats]. / Vliianie alkogolia na soderzhanie retseptorov polovykh steroidov v gipotalamuse i gipofize samtsov krys.

In experimental dipsomania model (formation of physical dependence by method of intensive alcoholization) we have studied receptor binding of testosterone (T) and estradiol (E2) in the hypothalamus and pituitary body of mature male rats. Administration (at 10 and 16 h) of 25% ethanol-saline solution at a dose of 7.5 g/kg of body weight in the course of 5 days significantly decreased serum T level but did not change serum LH and FSH levels. Essential reduction of the nuclear androgen receptors in the preoptic-anterior hypothalamic area (POA), mediobasal hypothalamus (MBH) and adenohypophysis was noted in alcohol-treated rats. Unlike androgen receptors the number of the nuclear E2-binding sites in PaO was significantly increased in these males. Thus the results of the present paper demonstrate that multiple administration of ethanol stipulates deficit of serum T, androgen receptors in MBH and pituitary body that possibly results in separation of negative feedback mechanism between the gonads and pituitary body. Increase of specific binding of E2 to nuclear receptors in PoA might appear to explain feminization of alcohol-treated rats.

[Hypothalamic receptors of sex hormones in the mechanism of the sexual differentiation of the brain in rats]. / Gipotalamicheskie retseptory polovykh gormonov v mekhanizme polovoi differentsirovki mozga u krys.

Studies have been made on the content of receptors of estradiol (E2) and testosterone (T) in cytoplasmic and nuclear fractions of the hypothalamus of male and female rats during neonatal development, as well as in adult females after androgenization in neonatal period and adult males castrated within 3 days of postnatal life. It was shown that both E2 and T are present in the blood serum of male and female newborn rats. In female hypothalamus, only E2 receptors were found, whereas in males both types of receptors were revealed, their content being higher than in females. In adult animals subjected to changes in the level of sex hormones in the blood during early neonatal period, changes in concentration of the receptors in the hypothalamic centres of regulation of tonic and cyclic secretion of gonadotropins were found. The data obtained presumably reveal the role of receptors of sex hormones in sex differentiation of the brain.

[Sex hormone receptors in the hypothalamus and their role in the sexual differentiation of the brain of male rats]. / Retseptory k polovym gormonam v gipotalamuse i ikh rol' v polovoi differentsirovke mozga u krys-samtsov.

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.

[Cytoplasmic and nuclear receptors of estradiol in the hypothalamus and cerebral cortex of female rats in the neonatal period]. / Tsitoplazmaticheskie i iadernye retseptory éstradiola v gipotalamuse i kore golovnogo mozga samok krys v neonatal'nom periode.

The content of estradiol receptors (E2) was studied in the cytoplasmic and nuclear fractions of the female rat hypothalamus and cortex during neonatal development. In the cytosol the E2-binding proteins, having a high capacity, include both true estradiol receptors and proteins identical with alpha-fetoprotein. True E2 receptors were found in the nuclear fraction: their concentration underwent almost no changes in hypothalamus and decreased from the 1st to the 5th day of postnatal development in cortex.

[Cytoplasmic and nuclear testosterone receptors in the hypothalamus of androgenized female and castrated male rats]. / Tsitoplazmaticheskie i iadernye retseptory k testosteronu v gipotalamuse u androgenizirovannykh samok i kastrirovannykh samtsov krys.

Receptors for testosterone (T) in the preopticoanterior hypothalamus (PO) and in the arcuate nucleus and median eminence (ARC + ME) were examined in neonatally androgenized female and neonatally castrated male rats. As a result of neonatal castration of males, the concentration of cytoplasmic and nuclear receptors for T in the PO dropped to an undetectable level. In the ARC + ME, the number of T-binding sites in the cytosole fraction remained unchanged, while that in the nuclear fraction decreased 2-fold. In the cytosole fraction of neonatally androgenized females, receptors for T were detectable only in the ARC + ME, the level of binding being not different from that seen in this hypothalamic area in intact and neonatally castrated males. At the same time in the nuclear fraction, receptors for T were detectable in both hypothalamic areas, the number of T-binding sites in the ARC + ME being 1.5 times less than in the PO. The data obtained attest to the involvement of receptors for T in sexual differentiation of the brain and regulation of gonadotropic function of the hypophysis.

[Dynamics of the changes in the content of testosterone and estradiol receptors in the hypothalamus of male rats in the course of sexual development]. / Dinamika izmeneniia soderzhaniia retseptorov k testosteronu i éstradiolu v gipotalamuse samtsov krys v khode polovogo razvitiia.

The content of receptors to testosterone and estradiol in hypothalamus of the male rats was studied during their sexual maturation (7, 14, 21, 28, 35 and 42 days). In all the age groups of animals the concentration of receptors to testosterone in the cytoplasmic and nuclear fractions of hypothalamus was at a relatively constant level, except in 7 day old males in which the minimal concentration of cytoplasmic and the maximal concentration of nuclear receptors were noted. The highest values of estradiol-binding sites in cytosol of hypothalamus were observed on the 7th and 14th days and in the nuclear fraction on the 28th, 35th and 42nd days of life. The binding of both the hormones with their receptors is a specific process characterized by a high affinity. A suggestion is put forward that receptors both to androgens and estrogens take part in the brain sexual differentiation.

[Estradiol receptors in the hypothalamus of androgenized female and castrated male rats]. / Retseptory éstradiolu v gipotalamuse u androgenizirovannykh samok i kastrirovannykh samtsov krys.

The content of receptors to estradiol was determined in cytosol of preoptical-anterior hypothalamic area and arcuate nucleus and medial eminence region of the neonatally androgenized females, neonatally castrate male and, for the control, in sexually mature intact rat males and females. The neonatal androgenization of females resulted in the decrease of the content of receptors in preoptical-anterior hypothalamic area and did no affect their content in arcuate nucleus and medial eminence region. The neonatal castration of males resulted in the increase of the content of receptors in preoptical-anterior hypothalamic area and its decrease in arcuate nucleus and medial eminence region.

[Dynamics of the content of estradiol cytoplasmic and nuclear receptors in the rat hypothalamus in the course of the estrous cycle and postnatal development]. / Dinamika soderzhaniia tsitoplazmatichekikh i iadernykh retseptorov k éstradiolu v gipotalamuse krys v khode éstral'nogo tsikla i postnatal'nogo razvitiia.

The content of receptors to estradiol in the cytoplasmic and nuclear hypothalamus fractions was studied in female rats during the postnatal development and oestral cycle. In the cytosol of 7 and 14 days old females and in the nuclear fraction of 7 days old females, E2-binding proteins having high capacity were identified as L-fetoprotein. The appearance of true receptors to E2 in the cytosol was shown in the 21 day old females and in the nuclear fraction in the 14 days old ones. In the other age periods until the 35th day, the parallel decrease in the content of both cytoplasmic and nuclear receptors was observed. The binding capacity of the cytoplasmic and nuclear receptors to estradiol in the preoptical area and the arcuate nucleus and median eminence area suffered marked changes with respect to different stages of the oestral cycle, and, within each stage, to day time.