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Appetite control and reproduction: leptin and beyond.
C J Small1, S A Stanley, S R Bloom
1Department of Metabolic Medicine, Division of Investigative Science, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
Seminars in Reproductive Medicine
|January 22, 2003
Summary
The hypothalamus regulates reproduction and energy balance through complex neurocircuitry. Key signals like leptin and the melanocortin system link nutrition to reproductive function, with ongoing research in humans.
Area of Science:
- Neuroendocrinology
- Metabolic Regulation
- Reproductive Physiology
Background:
- Hypothalamic neurocircuitry is crucial for regulating reproduction, energy intake, and expenditure, maintaining body weight and fertility.
- Reproductive function is closely linked to feeding; undernourishment down-regulates the reproductive axis via circulating factors and hypothalamic circuits.
- Leptin, a peripheral signal indicating body fat stores, links nutrition and reproduction by modulating hypothalamic neuropeptide circuits that influence gonadotropin-releasing hormone release and food intake.
Purpose of the Study:
- To explore the role of the melanocortin system in human reproduction, building on rodent studies.
- To investigate the connection between nutrition, energy balance, and reproductive function.
- To highlight the importance of peripheral signals like leptin and ghrelin in regulating these interconnected physiological processes.
Main Methods:
- Review of existing literature on hypothalamic neurocircuitry, leptin, melanocortin system, and ghrelin.
- Analysis of findings from rodent models and their translation to human physiology.
- Examination of genetic mutations (e.g., MC4 receptor, AgRP) and their impact on obesity and anorexia nervosa.
Main Results:
- Mutations in the melanocortin MC4 receptor are prevalent in morbid obesity (up to 4%).
- Agouti-related peptide gene mutations are found in some anorexia nervosa patients.
- Melanocortin system activation via intranasal administration of a fragment decreases adiposity in humans, suggesting a role in energy balance.
Conclusions:
- The melanocortin system's influence on human reproduction requires further investigation, despite its established role in rodents and impact on energy balance.
- Peripheral signals like leptin and ghrelin are critical regulators of reproduction, food intake, and energy expenditure, acting directly or via hypothalamic feedback.
- Understanding these neurocircuitries and signals is key to addressing metabolic and reproductive disorders.