[Morphofunctional state of reproductive system of ageing male rats in case of using nanocerium].

The influence of nanocrystalline cerium dioxide (NCD, 1 and 100 mg/kg per os daily for 10 days) on morphofuctional state of reproductive system was investigated in ageing male rats. It has been established that activation of hormone-producing testicular Leydig's cells, as well as of secretory and proliferative processes in prostate, underlies the stimulating effect of NCD at a dose 1 mg/kg on hormonal function of testis and spermatogenesis of ageing male rats. NCD used at a dose 100 mg/kg had no significant effect on the assessed indices of morphofuctional state of reproductive system.

[The dynamics of hormonal changes in female rats exposed to chronic stress and androgen excess during pubescence].

The dynamics of blood plasma corticosterone, testosterone and androstenedione levels and their reaction to acute stress (30 min immobilization) in 35-, 40- and 45-day old female rats exposed to chronic stress (daily 30-min immobilization from 35th to 45th day of life) and/or to excess of exogenous androgens (implantation of capsules with testosterone to 33-day old animals) during pubescence was studied. Both control and experimental females in all age groups responded to acute stress by significant elevation of blood plasma corticosterone levels. At the end of the chronic stress session, the extent of adrenals activation in response to acute dosed stress was lowered in androgenized 45-day old females and increased gradually in stressed ones. After acute stress, the blood plasma testosterone level decreased in control 35-day old females and rose - in androgenized females against 10-fold rising of basal hormonal level. In 40-day old control females as well as in androgenized ones exposed to chronic stress during 5 days, the acute dosed stress did not result in significant changes of blood plasma testosterone and elevated blood plasma androstenedione. Stressed 40-day old females with increased basal androstenedione secretion did not respond to acute stress by the hormone level changes while blood plasma testosterone declined significantly. At the end ofpubescence (on the 45th day of life), acute stress did not affect the blood plasma testosterone level in control and androgenized animals, while decreased it in stressed females and increased - in androgenized rats exposed to chronic stress against elevated basal level of the hormone. The conclusion is made about possible functional relationship between the changes in hormonal homeostasis during pubescence and development of reproductive system in mature animals.

[Effect of chronic stress during puberty on the reproductive system of female rats with experimental hyperandrogenicity].

Effects of chronic stress (daily 30-min immobilization) on 35-45 days of life and its combination with androgenization (implantation of testosterone-containing capsules on 33rd day of life) on reproductive system of 2.5 month old female rats were studied. The term of sexual maturation, estrous cycles regularity and structure, blood plasma levels of testosterone, progesterone and androstenedione as well as ovarian histology were examined. Androgenization resulted in the blood plasma testosterone level increase and the androstenedione level decrease, development of oligo- or anovulatory condition characterized by disorders or discontinuation in estrous cyclicity. We also detected abrupt reduction or absence of postovulatory luteal bodies, cysts formation and ovarian interstitial tissue overgrowth. All experimental animals had normal blood plasma corticosterone level. Stressed rats had no considerable changes in reproductive system except of some cyclicity disorders. Stressed against androgenization rats demonstrated delayed pubescence, an increased number of ovarian cysts along with attenuation ofandrogenization-caused negative effects on the sexual cyclicity.

[Enhancing effect of androgen receptor antagonist on gonadotropic inductors of ovulation in rats with polycystic ovaries].

Hormonal indices, phase pattern of estrous cycles, and histological structure of the ovaries were studied in female rats with polycystic ovaries caused by subcutaneous implantation of Silastic capsules with testosterone after consecutive treatment with non-steroid antiandrogen, flutamide (flutafarm), urinary FSH (menopur) and HCG (choragon). It was shown that while the plasma testosterone level was increased, administration of the drugs in subtherapeutical doses interrupted persistent diestrus, renewed estrous cycle, gonadal and uterine weights, induced appearance of postovulatory luteal bodies and restored fertility. Therefore, antiandrogen potentiation of pharmnnaco-dynamic effect of the gonadotropins with regard to their ability to ovulation induction was found out.

Prenatal dexamethasone prevents early and long-lasting neuroendocrine and behavioral effects of maternal stress on male offspring.

The hypothesis on the mediating role of hypothalamic-pituitary-adrenocortical (HPA) hormone secretion in neuroendocrine, neurochemical and behavioral alterations generated by prenatal stress in male rat offspring was tested in this study with dexamethasone (Dex) used for suppression of HIPA stress responses. Pregnant dams were being restrained daily for 1 h over the last week of gestation. In male offspring this resulted in attenuation of sex-specific pattern of the protein fractions (on the 5th postnatal day), steroid aromatase activity (on the 10th postnatal day) in the brain preoptic area, and in a decrease of male copulatory behavior, hypothalamic noradrenaline and plasma corticosterone responses to an acute stress, an increase in HPA responses to noradrenergic stimulation and other effects in adulthood. All those changes were prevented with prenatal Dex in a dose of 0.1 mg/kg b.w. injected 30 min prior to restraining pregnant dams. As such, HPA hormone secretion mediates alterations of programming of brain development induced by prenatal stress.

[Calcium-dependent mechanisms of stress disorders and noradrenergic responses of the hypothalamo-pituitary-adrenal system in neonatally androgenized female rats].

The effects of neonatal administration ofverapamil, a calcium L-type channel blocker, on the stress and noradrenergic responses of hypothalamo-pituitary-adrenal (HPA) axis in adult female rats with anovulatory syndrome induced by neonatal androgenization have been studied. There was no adrenocortical response to an acute stress nor noradrenaline infusion in the 3rd brain ventricle in females with persistent estrus. Verapamil pretreatment completely restored the adrenocortical responses to normal level. No changes were found in studied parameters following treatment with verapamil alone. These results demonstrate possible involvement of calcium signalling in pathogenesis of the disorders of HPA function in adult female rats, induced by neonatal androgenization.

[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.

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.

Early and long-term neuroendocrine effects of prenatal stress in male and female rats.

The effects of maternal stress, termed prenatal stress (PNS) on the neuroendocrine regulation of reproduction and the stress reactivity of offspring were studied in rats. PNS prevented the formation of sexual dimorphism in catecholamine levels, aromatase activity, and androgen 5alpha-reductase activity in the preoptic area of the brain and the mediobasal hypothalamus in 10-day-old rats. The morphological correlate of the functional lesions induced by PNS consisted of the elimination of gender-related differences in the volumes of neuron nuclei in the suprachiasmatic nucleus. Prenatal stress altered the stress and adrenergic reactivities of the hypothalamo-hypophyseal-adrenal system in mature males and females. The long-term effects of PNS were regarded as a consequence of the disruption of the hormone-neurotransmitter imprinting of the neuroendocrine system.

[The effect of prenatal stress on the development of hypophyseal gonadotropic function in male rats]. / Vliianie prenatal'nogo stressa na stanovlenie gonadotropnoi funktsii gipofiza u samtsov krys.

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.

[Recovery of various parameters of the functional state of the reproductive system in thymectomized rats as affected by thymic membrane factor]. / Vosstanovlenie nekotorykh pokazatelei funktsional'nogo sostoianiia reproduktivnoi sistemy u timéktomirovannykh krys pod vliianiem membrannogo faktora timusa.

Ten-month-old male rats thymectomized in early post-puberty were ascertained to have lower plasma luteinizing and testicular hormones and higher testicular steroid dehydrogenase activity. Following 24 hours of administration of a thymocyte membrane structural agent, pituitary gonadotropic and gonadal androgenic functions became normal. There was no agreement between the hormonal parameters and the levels of nucleic acids in the testes and prostate.

[The neuroendocrine mechanisms of the development of the anovulatory hyperandrogenic syndrome in rats]. / Neiroendokrynni mekhanizmy rozvytku anovuliatornoho syndromu hiperandrohennoho pokhodzhennia u shchuriv.

The anovulatory syndrome in adult female rats occurred after subcutaneous implantation of silastic capsules with testosterone. Acceleration of testosterone conversion into estradiol in the hypothalamus, suppression of pituitary LH responsiveness to LHRH, increase of blood plasma bioactive LH, estrous cycle disorder as well as morphological changes in ovaries demonstrate the alterations in neuroendocrine control of ovulation.

[The function of the reproductive system in x-ray-irradiated male rats after the transplantation of a culture of testicular cells from newborn piglets]. / Stan reproduktyvnoï systemy u renthenoprominenykh samtsiv shchuriv pislia transplantatsiï kul'tury klityn sim'ianykiv novonarodzhenykh porosiat.

The effect exerted by transplantation of the 5 day culture of testicles from newly born piglets on the hypogonadal state of mature X-ray irradiated (3 Gy) rats was studied. It has been found that a month after transplantation (two months after irradiation) the hypogonadal state disappeared for a while, which is confirmed by normalization of the weight of seminal vesicles, content of testosterone and biologically active lutropine, restoration of the reproductive function of rats. No significant changes in steroidogenesis activity have been found, which proves a substituent character of transplantation. The effect disappears three months later but certain restoration of the content of nucleic acids in the testicles is observed.

[Effect of 131I incorporation on the status of the reproductive system in male rats and the dose-dependent effect]. / Vliianie inkorporatsii 131I na sostoianie reproduktivnoi sistemy samtsov krys dozozavisimogo éffekta.

Radioactive 131I was injected in single doses 9.25, 37, and 92.5 kBq to prepubertal (30-day-old) male rats. Iodine incorporation in doses 37 and 92.5 kBq resulted in some functional changes in the reproductive system of mature rats: blood testosterone level increased, its hypothalamic aromatization intensified, and biologically active LH level in the blood dropped. Incorporation of 9.25 kBq of 131I had no effect on male reproductive system. A possibility of direct injury to rat testicles by 131I incorporation is suggested.

[The functional activity of the hypothalamo-hypophyseal-gonadal system in male rats in the late periods after x-ray irradiation]. / Funktsional'naia aktivnost' gipotalamo-gipofizarno-gonadnoi sistemy u samtsov krys v otdalennye sroki posle rentgenovskogo oblucheniia.

The hypothalamo-hypophysis-gonad system was studied in male rats 1, 3 and 6 months after external irradiation with doses of 2 and 3 Gy. Irradiation with a dose of 3 Gy was shown to cause a decrease in the level of LH and testosterone in blood plasma, impairment of steroidogenesis in the testes and diminution of their mass. All this was most pronounced 6 months after X irradiation. The morphofunctional status of prostate, inhibited by X radiation, was restored by that time.

[The role of testosterone metabolism in the hypothalamus in regulating the gonadotropic function of the hypophysis in male pre- and postpubertal rats]. / Rol' metabolizma testosterona v gipotalamuse v reguliatsii gonadotropnoi funktsii gipofiza u samtsov krys pre- i postpubertatnogo vozrasta.

Experiments were staged on immature (21 days) and mature (3.5 mos.) Wistar male rats to investigate the influence of the aromatase inhibitor 1, 4, 6-androstatriene-3, 17-dione on the activity of the aromatase and 5 alpha-reductase enzymatic complexes of the hypothalamus and the blood levels of LH and testosterone (T). The formation of 5 alpha-dehydrotestosterone against a background of aromatase activity inhibition was increased in mature rats and was unchanged in immature animals. The blood levels of LH and T were increased, the reaction of LH in immature animals being more marked. A conclusion has been made of a role of T aromatic transformations in the hypothalamus in tonic inhibition of LH secretion by endogenous T and a possible involvement of this mechanism in the maturation of male rats.

[Androgen status in rabbits after long-term administration of non-steroid androgen antagonist niftolid]. / Androgennyi status u krolikov v usloviiakh prodolzhitel'nogo vvedeniia nesteroidnogo antiandrogena niftolida.

Niphtholid (25 mg/kg/dl for 60 days) significantly increases the LH and testosterone blood levels but has no marked effect on ++androstenedione and testosterone-estradiol-binding globulin levels in Chinchilla++ mature rabbits. The concentration of latter was elevated against a background of low testosterone and androstenedione and high LH levels in the castrated rabbits. The obtained results show that niphtholid exerts a continuous stimulating and pronounced effect on the rabbit pituitary-gonadal axis and simultaneously prevents the manifestation of suppressing androgen effect on testosterone-estradiol-binding globulin contents in the organism.

[Specific binding of androgens by the skin in hirsutism of ovarian genesis]. / Spetsificheskoe sviazyvanie androgenov kozhei pri girsutizme ovarial'nogo geneza.

The role of raised skin sensitivity to circulating androgens in the pathogenesis of hirsutism, determined by the syndrome of polycystic ovaries, was studied. A two-fold increase in the specific binding of 3H-methyltrienolone++ was noted in the cytosol fraction of the public skin of women suffering from hirsutism as compared to healthy women using saturation analysis. The specific binding of androgens indicated an increase in the content of androgen receptors of the skin in hirsutism.