Modern concept of neuroendocrine and epigenetic regulation of the onset of puberty and sexual development. Translational studies on the role of the KISS/KISS1R system

Background. Kisspeptin system plays a fundamental role in the neuroendocrine control of hypothalamic-pituitary-gonadal axis, initiation of puberty and fertility. These observations suggest that kisspeptin system is a potential novel therapeutic and diagnostic approach for treating children with delayed puberty and hypogonadotropic hypogonadism and is currently a focus of translational research. Objective. Estimation of the functional activity of the kisspeptin system and its role in the genesis of delayed puberty. Design and methods. The experimental part of the study included 53 male Wistar rats. The clinical part of the study included 75 somatically healthy boys. The expression levels of kisspeptin receptors KISS1R in central androgen dependent tissues were evaluated by immunohistochemical method. Kisspeptin receptor levels and serum levels of kisspeptin were assessed by ELISA. Serum levels of luteinizing hormone and follicle-stimulating hormone were evaluated by chemiluminescent immunoassay. Results. A negative regulatory feedback was established between the concentration of kisspeptin and plasma testosterone both in the experimental and clinical parts of the study. Hypotestosteronemia leads to a significant decrease in the number of kisspeptin receptors in androgen-dependent tissues. Low testosterone levels cause degenerative-dystrophic changes in the neurons of the medial arcuate nucleus of the hypothalamus, which undergo partial regression during testosterone therapy. The level of kisspeptin significantly increases in individuals with delayed puberty. Serum kisspeptin levels exceeding 16.9 pg/ml is a reliable predictor of delayed puberty. Conclusion. Obtained results indicate the importance of translating them into clinical practice in order to substantiate novel diagnostic and therapeutic approach to the management of central forms of delayed puberty.

boys, gonadotropin-releasing hormone, hypogonadism, kisspeptin, puberty, testosterone

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