Multiple coupling of neurohormone receptors with cyclic AMP and inositol phosphate production in anterior pituitary cells

Abstract

Regulation of adenohypophyseal hormone secretions has been shown to involve cyclic AMP production, modulation of phosphatidyl inositol diphosphate breakdown and Ca 2+ mobilization. Various neurohormone receptors are positively or negatively coupled to adenylate cyclase activity in anterior pituitary cells. The effects of these neurohormones on adenylate cyclase activity are consistent with the effect on hormone secretions, suggesting that modulation of the enzyme activity is actually involved in the regulation of adenohypophyseal secretions. Thus DA inhibits, whereas VIP stimulates adenylate cyclase activity of the same cell type, which, according to the effect of these neurohormones on prolactin secretion, appear to be lactotrophs. On the other hand, SRIF inhibits, whereas GRF stimulates the adenylate cyclase activity of another cell type, namely somatotrophs, whereas CRF appears to act on a third cell type, corticotrophs. Peripheral hormones have been shown to modulate the sensitivity of anterior pittuitary cells to these neurohormones. Estradiol long-term treatment has an anti-dopaminergic effect on prolactin secretion. The steroid also suppresses the dopamine inhibition of adenylate cyclase. This effect appears selective to the DA inhibition, since A II inhibition of the enzyme is only partially reduced, whereas the somatostatin inhibition is markedly increased. Peripheral hormones seem to affect the sensitivity of adenohypophyseal cells not only by modulating the number of receptors for a given neurohormone but also by interfering with the coupling mechanisms of these receptors. A II and DA inhibit the adenylate cyclase activity of lactotroph cells. The prolactin stimulation induced by angiotensin is not consistent with the effect of the peptide on adenylate cyclase. Pre-treatment with Bordetella pertussis toxin completely suppresses the DA and A II inhibitions of adenylate cyclase activity. The toxin also reverses the DA induced inhibition of prolactin secretion. In contrast the angiotensin stimulation of prolactin release is not affected. In fact, angiotensin markedly stimulates the production of inositol phosphates and this effect is totally unaffected by pertussis toxin. Furthermore, in addition to an inhibition of adenylate cyclase, DA is able to inhibit the A II-induced inositol phosphate production and this effect is blocked by pertussis toxin. The D 2 DA receptor is thus negatively coupled with adenylate cyclase and phospholipase C. The GTP binding protein(s) involved in these couplingscould be G i and/or G o since they are both present in anterior pituitary cells and are both pertussis toxin substrates.