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.

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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)

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 contents of dopamine, serotonin, and noradrenaline in rat fetuses developing under the conditions of their deficiency induced by administration of α -methyl-para -tyrosine to females during 11th to 16th or 20th day of pregnancy and in fetuses, whose mothers were given saline at the same time, were determined using HPLC with subsequent electrochemical detection. Administration of α -methyl-para -tyrosine led to decreased levels of dopamine and noradrenaline in the areas of migration of GnRH-neurons in fetuses on days 17 and 21 of prenatal development. The concentration of serotonin remained unchanged, except in the head nasal area in males on day 21. The areas of interaction between the brain catecholaminergic systems and migrating and differentiating GnRH-neurons were determined by double immunohistochemical labeling. Close topographical location of GnRH-immunoreactive neurons and tyrosine hydroxylase-immunoreactive in the area of nucleus accumbens on days 17 and 20, as well as in the median eminence on day 20. The GnRH concentration in the caudal areas of migration of GnRH-neurons under the normal conditions and in the case of catecholamine deficiency was determined using radioimmunoassay. After administration of α -methyl-para -tyrosine the GnRH concentration in the anterior hypothalamus decreased in females. The data obtained suggest the involvement of catecholamines in the regulation of development of GnRH-Neurons during prenatal development. In addition, the adequacy and efficiency of the used model of catecholamine deficiency for studying the development of such neurons was confirmed.