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.
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)
Recent progress in neuroendocrinology provided a basis for the formulation of the integral strategy for the systemic treatment of endocrine diseases. This review presents experimental and clinical evidence of the presence in the hypothalamus of specific receptors of hormones produced by the peripheral endocrine glands and trophic pituitary hormones. Synthesis of specific hypothalamic substances (releasing hormones) maintains the interplay between the neural and endocrine structures. The positive and negative feedback mechanisms in the body ensure the stable functioning of all its organs and systems.
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