kiss1-protein--human and Metabolic-Syndrome

Sex steroid hormones, most notably estradiol, play a pivotal role in the sex-specific organization and function of the kisspeptin system. Endocrine--disrupting compounds are anthropogenic or naturally occurring compounds that interact with steroid hormone signaling. Thus, these compounds have the potential to disrupt the sexually dimorphic ontogeny and function of kisspeptin signaling pathways, resulting in adverse effects on neuroendocrine physiology. This chapter reviews the small but growing body of evidence for endocrine disruption of the kisspeptin system by the exogenous estrogenic compounds bisphenol A, polychlorinated biphenyl mixtures, and the phytoestrogen genistein. Disruption is region, sex, and compound specific, and associated with shifts in the timing of pubertal onset, irregular estrous cycles, and altered sociosexual behavior. These effects highlight that disruption of kisspeptin signaling pathways could have wide ranging effects across multiple organ systems, and potentially underlies a suite of adverse human health trends including precocious female puberty, idiopathic infertility, and metabolic syndrome.

Topics: Animals; Benzhydryl Compounds; Estradiol; Female; Genistein; Humans; Infertility; Kisspeptins; Menstrual Cycle; Metabolic Syndrome; Neurosecretory Systems; Phenols; Phytoestrogens; Puberty, Precocious; Sexual Behavior; Signal Transduction

Metabolic syndrome (MetS) clusters cardiovascular and metabolic risk factors along with hypogonadism and erectile dysfunction. Lifestyle modifications including physical exercise (PhyEx) are well-known treatments for this condition. In this study, we analyzed the effect of PhyEx on hypothalamic-pituitary-testis axis and erectile function by use of an animal MetS model, previously established in rabbits fed a high-fat diet (HFD). Rabbits fed a regular diet (RD) were used as controls. A subset of both groups was trained on a treadmill. HFD rabbits showed typical MetS features, including HG (reduced T and LH) and impairment of erectile function. PhyEx in HFD rabbits completely restored plasma T and LH and the penile alterations. At testicular and hypothalamic levels, an HFD-induced inflammatory status was accompanied by reduced T synthesis and gonadotropin-releasing hormone (GnRH) immunopositivity, respectively. In the testis, PhyEx normalized HFD-related macrophage infiltration and increased the expression of steroidogenic enzymes and T synthesis. In the hypothalamus, PhyEx normalized HFD-induced gene expression changes related to inflammation and glucose metabolism, restored GnRH expression, particularly doubling mRNA levels, and regulated expression of molecules related to GnRH release (kisspeptin, dynorphin). Concerning MetS components, PhyEx significantly reduced circulating cholesterol and visceral fat. In multivariate analyses, cholesterol levels resulted as the main factor associated with MetS-related alterations in penile, testicular, and hypothalamic districts. In conclusion, our results show that PhyEx may rescue erectile function, exert anti-inflammatory effects on hypothalamus and testis, and increase LH levels and T production, thus supporting a primary role for lifestyle modification to combat MetS-associated hypogonadism and erectile dysfunction.

Topics: Animals; Blood Glucose; Cholesterol; Dynorphins; Erectile Dysfunction; Gonadotropin-Releasing Hormone; Hypogonadism; Hypothalamo-Hypophyseal System; Kisspeptins; Luteinizing Hormone; Macrophages; Male; Metabolic Syndrome; Physical Conditioning, Animal; Rabbits; Testis; Testosterone; Triglycerides; Tumor Necrosis Factor-alpha