Multiple hormonal control of pars intermedia cell activity

Abstract

In rat pars intermedia cells, the rate of α-melanocyte-stimulating hormone (α-MSH) secretion was so far known to result from a balance between the stimulatory effect of β-adrenergic agonists and the inhibitory influence of dopaminergic substances. Recently, we have identified a second stimulatory substance, namely corticotropin-releasing factor (CRF). CRF is a potent stimulator of pars intermedia adenylate cyclase activity, cAMP accumulation and α-MSH release. A requirement for calcium ions was observed on basal as well as on CRF-induced α-MSH secretion. The β-adrenergic and CRF effects on adenylate cyclase activity, as well as the dopamine inhibition of adenylate cyclase activity, are potentiated by guanine nucleotides (GTP). Stimulation of the β-adrenergic receptor with isoproterenol causes a rapid loss in cAMP responsiveness, which can be completely blocked by β-adrenergic antagonists and partially prevented by dopamine. These findings suggest that CRF should now be considered, in addition to β-adrenergic agents, as a stimulator of the activity of pars intermedia cells and that cAMP is also involved as mediator of its action. Changes of receptor sensitivity, as well as interaction of the two stimulatory receptors with the inhibitory dopaminergic receptor, are involved in the fine control of pars intermedia cell activity. All three receptors appear to exert their action through a common pathway, namely changes of adenylate cyclase activity.