Part of the book: Neurodegenerative Diseases
The functional changes in hormone-sensitive adenylyl cyclase (AC) signaling system of the central nervous system (CNS) and periphery play a crucial role in etiology and pathogenesis of diabetes mellitus (DM). The identification of these changes in AC signaling system and the abnormalities in AC signaling network are necessary for creation of the new strategies to treat and prevent diabetic pathology. In this chapter, our data and the results of other authors on the changes in hormone-sensitive adenylyl cyclase signaling system (ACSS) in the diabetic brain and heart and on their contribution to etiology and pathogenesis of DM and its complications, diabetic cardiomyopathy in particular, are presented and analyzed, and the promising approaches to treat DM and its complications, which are based on the restoration of AC signaling cascades and their functional interaction, are discussed.
Part of the book: Evolutionary Physiology and Biochemistry
There is evidence that the mass and metabolic status of the adipose tissue that produces adipokines significantly affect the activity of the hypothalamic-pituitary-gonadal (HPG) axis and the synthesis of testosterone. This is due to the fact that adipokines, such as leptin, adiponectin, visfatin and resistin have an important role in the regulation of the male HPG axis and steroidogenesis in the testes. The regulation of the HPG axis by adipokines can be carried out both through the changes the plasma levels of adipokines (a systemic regulation) and through the changes in the expression and activity of adipokines in the pituitary and testes, the components of the HPG axis (an autonomous regulation). This review presents the comprehensive analysis of the involvement of leptin, adiponectin, resistin and visfatin in the regulation of the male HPG axis and the testosterone production, as well as of the possible mechanisms of this regulation. The role of adipokines in the dysregulation of the male reproductive system and the impaired steroidogenic activity in the testes in obesity and type 2 diabetes mellitus are also discussed.
Part of the book: Advances in Testosterone Action
In clinic, the luteinizing (LH) and follicle-stimulating (FSH) hormones and human chorionic gonadotropin (hCG) are used to treat reproductive dysfunctions and in assisted reproductive technology. They are the αβ-heterodimeric complexes and specifically bind to ectodomain of G protein-coupled LH and FSH receptors. This leads to activation of many signaling cascades; some of which are responsible for steroidogenesis, folliculogenesis, and spermatogenesis, while the others, such as β-arrestin pathways, trigger the downregulation of gonadotropin receptors. A low selectivity of the intracellular signaling of gonadotropins and a large number of their isoforms are the main causes of undesirable effects of gonadotropins, limiting their clinical applications. Unlike gonadotropins, the low-molecular-weight (LMW) ligands interact with an allosteric site located in the transmembrane domain of the LH and FSH receptors and selectively activate the certain signaling pathway, preventing a number of side effects of gonadotropins. The LMW ligands are characterized by activity of the full and inverse agonists and neutral antagonists, as well as the positive and negative modulators, and they have the in vivo activity, including when administered orally. This review focuses on the advances in the development of LMW allosteric ligands of the LH and FSH receptors and the prospects for their use in reproductive medicine.
Part of the book: Innovations In Assisted Reproduction Technology