Progesterone modulation of D5 receptor expression in hypothalamic ANP neurons, the role of estrogen

Aberrant responses to dopamine consequent to a reduction of D1-like receptors in critical regions of the brain have been implicated in schizophrenia. Whereas estrogen may protect against the onset and incidence of psychosis in the illness, the neurobiological effects of the ovarian steroid remain unclear. Recently we have shown that estrogen augments the expression of D5 receptors, a member of the D1-like receptor family, in central neurons and enhances the functions of the host cells. Employing rat hypothalamic neuron cultures, we report here that another important ovarian steroid, progesterone, also augments dopamine D5 receptor expression in hypothalamic atrial natriuretic factor (ANP) neurons. However, unlike the effect of estrogen, progesterone acts indirectly through potentiating estrogen-mediated changes that include enhancement of D5 receptor expression, immunoreactive (ir)-ANP release and pro-ANP mRNA abundance. We conclude that whilst progesterone has little effect by itself, the steroid works in synergism with estrogen to augment the function of ANP neurons. The possibility that progesterone may further enhance the protective effect of estrogen against the incidence of psychosis in schizophrenia now needs to be considered.