Ionic, neuronal and endocrine influences on the proopiomelanocortin system of the hypothalamus

Increasing evidence supports a neurotransmitter or a neuromodulator action for peptides derived from proopiomelanocortin in the hypothalamus. Peptide release involves sodium, potassium and calcium ion channels and is dependent on the presence of extracellular calcium ions at the time of depolarisation of neuronal membranes. Dopaminergic and gamma-aminobutyric acid-containing neuronal systems inhibit POMC-derived peptide release from the hypothalamus through D2-dopamine and GABAA receptors, respectively. Serotoninergic mechanisms exert a biphasic effect on peptide release being directly stimulatory at low concentrations of serotonin and indirectly inhibitory at higher concentrations via interactions with the endogenous dopaminergic system. Cholinergic and glutamergic drugs stimulate peptide release through nicotinic and N-methyl-D-aspartate receptors, respectively. Finally, circulating steroids regulate the hypothalamic POMC system with testosterone stimulating POMC gene expression whilst oestradiol and glucocorticoids induce an inhibitory control.