Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Effects of environmental endocrine disruptors and phytoestrogens on the kisspeptin system. 2355 19

Adipose tissue produces factors, including adipokines, cytokines and chemokines which, when released, systemically exert endocrine effects on multiple tissues thereby affecting their physiology. Adipokines also affect the hypothalamic-pituitary-gonadal (HPG) axis both centrally, at the hypothalamic-pituitary level, and peripherally acting on the gonads themselves. Among the adipokines, leptin, adiponectin, resistin, chemerin and the peptide kisspeptin have pleiotropic actions on the HPG axis affecting male and female fertility. Furthermore, adipokines and adipose tissue-produced factors readily affect the immune system resulting in inflammation, which in turn impact the HPG axis, thus evidencing a link between metabolic inflammation and fertility. In this review we provide an overview of the existing extensive bibliography on the crosstalk between adipose tissue-derived factors and the HPG axis, with particular focus on the impact of obesity and the metabolic syndrome on gonadal function and fertility.
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PMID:The impact of adipose tissue-derived factors on the hypothalamic-pituitary-gonadal (HPG) axis. 2685 2

We evaluated the effect of cafeteria diet (CAF) on the mRNA levels and DNA methylation state of feeding-related neuropeptides, and neurosteroidogenic enzymes in discrete hypothalamic nuclei. Besides, the expression of steroid hormone receptors was analyzed. Female rats fed with CAF from weaning increased their energy intake, body weight, and fat depots, but did not develop metabolic syndrome. The increase in energy intake was related to an orexigenic signal of paraventricular (PVN) and ventromedial (VMN) nuclei, given principally by upregulation of AgRP and NPY. This was mildly counteracted by the arcuate nucleus, with decreased AgRP expression and increased POMC and kisspeptin expression. CAF altered the transcription of neurosteroidogenic enzymes in PVN and VMN, and epigenetic mechanisms associated with differential promoter methylation were involved. The changes observed in the hypothalamic nuclei studied could add information about their differential role in food intake control and how their action is disrupted in obesity.
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PMID:Cafeteria diet differentially alters the expression of feeding-related genes through DNA methylation mechanisms in individual hypothalamic nuclei. 2847 74

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.
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PMID:Physical activity counteracts metabolic syndrome-induced hypogonadotropic hypogonadism and erectile dysfunction in the rabbit. 3064 74

Puberty is the process whereby an individual acquires the ability to reproduce, and the attainment of puberty in a timely manner is critical for both humans and livestock. For livestock, the initiation of puberty at the appropriate time aids in increasing lifetime productivity, thus maximizing profitability for producers. For humans, particularly females, early or late puberty is associated with several adverse health outcomes, including polycystic ovary syndrome, obesity, metabolic syndrome, osteoporosis, and psychosocial distress. Therefore, characterizing the mechanisms responsible for puberty onset would have a significant impact on human and animal health. It has been postulated that a group of neurons in the arcuate nucleus of the hypothalamus may play a role in puberty onset. These neurons contain kisspeptin, neurokinin B (NKB), and dynorphin and are often called KNDy neurons. Although the role of kisspeptin in puberty onset has been heavily researched, the involvement of NKB and dynorphin is not well defined. This mini-review focuses on the role of NKB in the initiation of puberty in female sheep. Stimulation of the receptor for NKB, NK3R, elicits LH secretion in a GnRH-dependent manner in prepubertal ewes, and both functional and neuroanatomical changes to the NKB system, particularly within the preoptic area, appear to occur as female sheep transition from a prepubertal to an adult state. Thus, NKB is likely an important component of puberty onset in sheep, although its integration with other systems that impact the pubertal process, such as photoperiod and nutrition, remains to be elucidated.
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PMID:Role of neurokinin B in ovine puberty. 3220 83