Physiology and gene regulation of the brain NPY Y1 receptor

Neuropeptide Y (NPY) is one of the most prominent and abundant neuropeptides in the mammalian brain where it interacts with a family of G-protein coupled receptors, including the Y1 receptor subtype (Y1R). NPY-Y1R signalling plays a prominent role in the regulation of several behavioural and physiological functions including feeding behaviour and energy balance, sexual hormone secretion, stress response, emotional behaviour, neuronal excitability and ethanol drinking. Y1R expression is regulated by neuronal activity and peripheral hormones. The Y1R gene has been isolated from rodents and humans and it contains multiple regulatory elements that may participate in the regulation of its expression. Y1R expression in the hypothalamus is modulated by changes in energetic balance induced by a wide variety of conditions (fasting, pregnancy, hyperglycaemic challenge, hypophagia, diet induced obesity). Estrogens up-regulate responsiveness to NPY to stimulate preovulatory GnRH and gonadotropin surges by increasing Y1R gene expression both in the hypothalamus and the pituitary. Y1R expression is modulated by different kinds of brain insults, such as stress and seizure activity, and alteration in its expression may contribute to antidepressant action. Chronic modulation of GABAA receptor function by benzodiazepines or neuroactive steroids also affects Y1R expression in the amygdala, suggesting that a functional interaction between the GABAA receptor and Y1R mediated signalling may contribute to the regulation of emotional behaviour. In this paper, we review the state of the art concerning Y1R function and gene expression, including our personal contribution to many of the subjects mentioned above.