Oestrogen modulates hypothalamic control of energy homeostasis through multiple mechanisms

The control of energy homeostasis in women is correlated with the anorectic effects of oestrogen, which can attenuate body weight gain and reduce food intake in rodent models. This review investigates the multiple signalling pathways and cellular targets that oestrogen utilises to control energy homeostasis in the hypothalamus. Oestrogen affects all of the hypothalamic nuclei that control energy homeostasis. Oestrogen controls the activity of hypothalamic neurones through gene regulation and neuronal excitability. Oestrogen's primary cellular pathway is the control of gene transcription through the classical oestrogen receptors (ERs) (ERalpha and ERbeta) with ERalpha having the primary role in energy homeostasis. Oestrogen also controls energy homeostasis through membrane-mediated events via membrane-associated ERs or a novel, putative membrane ER that is coupled to G-proteins. Therefore, oestrogen is coupled to at least two receptors with multiple signalling and transcriptional pathways to mediate immediate and long-term anorectic effects. Ultimately, it is the interactions of all the receptor-mediated processes in hypothalamus and other areas of the central nervous system that will determine the anorectic effects of oestrogen and its control of energy homeostasis.