Sexual behavior is a constituent of the reproductive function of the organism. In sexually mature individuals the synchronization of the level of sexual activity with the reaction of the hypothalamo-hypophyseo-gonadal system to the relevant environmental stimuli is a necessary condition for the preservation of the species. In this context, the study of the neuroendocrine mechanisms shaping a specific level of activity of sexual behavior is an important problem for investigators. The dependence of the level of sexual activity on the integrity of certain CNS structures (first of all, the olfactory bulbs, amygdala, hypothalamus, and hypophysis) has been established. It has been demonstrated that label sex steroids accumulate selectively, and the regulation of the function of the gonads on the negative feedback principle is also accomplished in these regions precisely. In addition to the participation of the sex steroids in the formation of a specific level of sexual activity, an important role has been established at the present time for luliberin (LHRH) producing system and the neurotransmitters. The stability of the functioning of the reproductive system depends on a multiplicity of factors of the internal and external milieu. Serious disturbances in its function are associated with the alteration in carbohydrate homeostasis underlying a disease such as diabetes mellitus. This is manifested in a reduction in the weight of the accessory sex glands, steroidogenic activity and spermatogenesis, in a change in the secretion of gonadotropins, as well as in a diminution of fertility and sexual behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Investigations to assess the state of the reproductive system in female rats in experimental streptozotocin (STZ)-induced diabetes have been a logical continuation of studies we have carried out previously [4, 5] to analyze the interrelationship of disturbances of the reproductive system and sexual behavior in male rats in diabetes. It is known that by contrast with males, cyclical changes in the activity of the reproductive system are characteristic for females. Consequently, it is not excluded that the differences observed in the norm in the regulation of the gonadotropic function of the hypophysis in male and female rats may explain the fact that males are in the main more sensitive to the hyperglycemic action of STZ than females [13]. In addition, some data point to nonidentical changes in the organism of males and females in the presence of an insulin deficit [10]. Bestetti et al. [7] have concluded, on the basis of the results of morphological and physiological investigations, that changes in the hypophysis are less clearly manifested in the females than the males. The interpretation of the results obtained by various investigators when studying the reproductive system in diabetic females has been complicated by the presence of cyclical changes.The disturbances in cyclicity in the severe forms of diabetes may be caused by the numerous disturbances of the hypothalamohypophyseogonadal axis, which includes both CNS structures and the ovarian level.A comprehensive investigation was carried out in this study of the of the functional activity of the hypothalamohypophyseogonadal system in female rats with streptozotocin-induced diabetes. The concentration of nuclear receptors of the sex hormones in the adenohypophysis and regions of the hypothalamus which participate in the regulation of the secretion of the gonadotropins through the feedback mechanism was determined for this purpose. In addition, the sensitivity of the hypophysis to luliberin (LH-RH) in ovariectomized female rats with compensatory administration of estradiol (E2) and progesterone was determined to exclude a possible disturbance in the secretion of steroids at the ovarian level in diabetes. MATERIALS AND METHODSThe experiments were carried out in white mongrel, sexually mature female rats, weighing 170-200 g, which were maintained in a controlled temperature regime (22-25*C) and controlled illumination (light from 0500 to 1900 h). In the course of the experiment all animals had free access to food and water. The intact cycling and ovariectomized females were administered STZ (intraperitoneally) in a dose of 60 mg per 1 kg of body weight in 0.2 ml of citrate buffer, pH 4.5. Only those rats in which the blood glucose concentration was no less than 12 mmole/liter were selected for the experimental group (at a level in the control females of 2.7-3.6 mmole/liter). Fourteen days after the induction of diabetes, vaginal smears were taken daily from the females to check estral cyclicity. Persistent diestrus (D) was observed in 65-80% of the diabetic ani...

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It is known that the disturbance in the functional activity of the reproductive system of the organism in diabetic laboratory animals is associated not only with destructive changes in the gonads, but with dysfunction of the hypothalamohypophyseal complex as well [11, 12]. It has been demonstrated that the decrease in the basal secretion of gonadotropins and sex hormones and the absence of its cyclical changes in female rats with experimental diabetes may be determined by disturbances in the central hypothalamic regulation of the reproductive system [6, 14]. The possibility of changes in the secretion of gonadotropins that are associated with a disturbance in the sensitivity of gonadotrops of the hypophysis to the action of luliberin (LH-RH) has not been excluded. Also, it is known from the literature that these disturbances are manifested to different degrees in male and female individuals [3]. The question as to the degree to which the disturbances arising in diabetes depend on the level of sex steroids and insulin in the organism remains controversial [4, 19]. Considering the fact that insulin may participate directly in the regulation of the function of the gonadotrops [2], we investigated under in vitro conditions its influence on the sensitivity of the hypophysis to LH-RH in a model of ovariectomized female rats with streptozotocin-induced diabetes which received estradiol as compensatory hormone therapy. MATERIALS AND METHODSThe experiments were carried out in white mongrel, sexually mature female rats, weighing 160-180 g, which were maintained in a controlled temperature regime (22-25~ and controlled illumination (light from 0500 to 1900 h). The animals were ovariectomized under ether anesthesia, and were administered streptozotocin (STZ) after 7 days in a dose of 60 mg per 1 kg of body weight in 0.2 ml of citrate buffer (pH 4.5), intraperitoneally, or the same volume of buffer. Rats in which the blood glucose concentration was greater than 12 mmole/liter were selected for the experimental group (in the control animals, 2.7-3.6 mmole/liter). The animals received estradiol benzoate (E2), 21-25 days after the administration of STZ, in a dose of 5/zg in 0.2 ml of olive oil. The rats were decapitated after 72 h; the adenohypophyses were extracted and were divided into two portions, and two halves from different hypophyses were each preincubated in 1 ml of medium 199, saturated in an atmosphere of 95 % 02 and 5 % CO 2, and containing 20 mmole HEPES and 20 mmole bacitracin (Serva). After changing the medium, the hypophyses were incubated at 37~ with constant agitation, with the addition of LH-RH (50 ng/ml) and/or insulin (24/xAU/ml) for 5 h, collecting aliquots of 20/zl each every hour for the subsequent determination of luteinizing (LH) and follicle stimulating (FSH) hormones; the medium was replaced by new medium after 4 h.The determination of the concentration of LH and FSH in the medium was carried out by radioimmunoassay, using NIDDK kits (USA). The concentration of the hormones was expressed in nanograms ...

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