Matvienko M. Morphofunctional stаtus of rat hypothalamic-gonadal complex in the interaction of kisspeptinergic and alpha-adrenergic systems and melatonin.

The present thesis deals with the indicators of cellular functional activity of the hypothalamic nuclei and gonads (the nuclear cross-sectional area of neurocytes and astrocytes of the preoptic and the arcuate hypothalamic nuclei; the nuclear cross-sectional area of Leydig cells and the the testicular tubule diameter) in rats of different ages with a special reference to blockade and activation of alpha-adrenergic and kisspeptinergic systems and melatonin administration. It has been found that the functional state of the elements of the hypothalamic-gonadal complex is determined not only by the kisspeptinergic and the alpha-adrenergic systems signly, but it's a result of their interaction. While the alpha-adrenergic system is the upstream one in the mechanisms of reproductive regulation than the kisspeptinergic system and it defines the activity level of the gonadotropic axis. At once it is proved that aforementioned systems change their comparative efficiency as mediators of inhibitive and activating effects of each other with age. that The kisspeptinergic system was shown to modulate the rat hypothalamic-gonadal complex at all tested ontogenetic stages. In 1-month-old animals the alpha-adrenergic system and the epiphysis mediate their effects through the kisspeptinergic system and they also are able to act directly on the hypothalamus and the gonads. But the epiphysis and the alpha-adrenergic system of 3-month rats influence on the hypothalamus bypassing the kisspeptinergic link. In 24-month animals the alpha-adrenergic system acts on the hypothalamus indirectly through the kisspeptinergic one and it also can influence directly. Melatonin has the inhibitive effect on the hypothalamic-gonadal complex of old rats by the feedback mechanisms. It is investigated that kisspeptin activates the cells of rat hypothalamic nuclei and the testicles, and the peptide-antagonist (P-234) makes the opposite effect on the above-mentioned links of the gonadotropic axis. It's shown that in all age groups of animals the combined administration of melatonin and kisspeptin induces the cellular activation, and the blocker of the kisspeptinergic receptors (P-234) together with melatonin does not considerably effect on the cellular activity of the hypothalamic nuclei. In 1- and 3-months animals there was inhibition of gonadal function after combined administration of the kisspeptinergic receptors blocker (P-234) and melatonin. Administration of melatonin and kisspeptin leads to even greater activation of the testicular function than melatonin only. In 24-months rats the inhibitory effect of melatonin on the gonadal function is partially abolished after combined administration of both kisspeptin and its antagonist (P-234). It is established that administration of the kisspeptinergic receptors blocker (P-234) together with mezaton results in abolition of mezaton activating effect. On the other hand, the combined administration of prazosin and kisspeptin completely abolishes the inactivating effect of prazosin, although the signs of activation, inherent to kisspeptin, occur only in some cases. After combined administration of the blockers and the activators of the alpha-adrenergic and the kisspeptinergic systems the effects of mezaton and prazosin are completely eliminated in the gonads due to oppositely directed influences of the kisspeptinergic receptors blocker (P-234) and kisspeptin in all age groups of the animals respectively. Keywords: hypothalamic-gonadal complex, arcuate nucleus, preoptic nucleus, neuron, astrocyte, kisspeptin, kisspeptin antagonist (P-234), melatonin, mezaton, prazosin.