Preliminary characterisation of the neuropeptide melanin concentrating hormone in humans

Melanin concentrating hormone (MCH) is an orexigenic neuropeptide expressed centrally in the zona incerta and lateral hypothalamus. Evidence from rodent studies implicates hypothalamic MCH in the modulation of varied and diverse physiological functions most notably in energy homeostasis but also emerging as a candidate mediator in reproductive activities. These two aspects of normal physiology are intimately related though the pathways through which they integrate are only just being explored. Currently little is known about the actions, sources or targets of peripheral or circulating MCH. This study is the first to describe normal physiological concentrations of circulating MCH in humans. Particular emphasis has been devoted to aspects which might further understanding of the dual roles of circulating MCH in energy balance and reproductive function. A primary objective was to develop and validate a tool with which to quantifiably measure circulating MCH concentrations since previous work in this area has failed to reconcile this objective. Following the successful validation of a radioimmunoassay (RIA), three studies were undertaken with human subjects drawn from 3 distinct sample populations. The chief objectives were 1) to detect changes in circulating MCH post-prandial in association with other metabolic markers of energy homeostasis; 2) to determine associations between circulating MCH concentrations and resting metabolic rate (RMR); and 3) to detect changes in circulating MCH concentrations during the menstrual cycle. The results indicate that circulating MCH concentrations may be involved in glucose homeostasis since there were associations between the post-prandial MCH and the post-prandial insulin response. Circulating MCH may also convey information regarding the nutritional status of the individual, though this appears to be influenced by a combination of gender and adiposity status. Circulating MCH concentrations remained stable over the course of the menstrual cycle and were not strongly aligned to RMR. Whilst there were emergent patterns and trends there were also inconsistencies between the sample populations. This initial characterisation may be constructive for future exploration of the physiological relevance of circulating MCH in humans.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The roles of melanin-concentrating hormone in energy balance and reproductive function: are they connected?

Melanin concentrating hormone (MCH) is an anabolic neuropeptide with multiple and diverse physiologic functions including a key role in energy homeostasis. Rodent studies have shown that ablation of functional MCH results in a lean phenotype, increased energy expenditure and resistance to diet-induced obesity. These findings have generated interest amongst pharmaceutical companies vigilant for potential anti-obesity agents. Nutritional status impacts on reproductive physiology and behaviours thereby optimising reproductive success and the ability to meet energetic demands. This complex control system entails integration of direct or indirect peripheral stimuli with central effector systems and involves numerous mediators. A role for MCH in the reproductive axis has emerged giving rise to the premise that MCH may serve as an integratory mediator between those discrete systems which regulate energy balance and reproductive function. Hence this review focuses on published evidence concerning a) the role of MCH in energy homeostasis and b) the regulatory role of MCH in the reproductive axis. The question as to whether the MCH system mediates the integration of energy homeostasis with the neuroendocrine reproductive axis and if so by what means has received limited coverage in the literature; evidence to date and current theories are summarised here