Differential regulation of MAP kinase activity by corticotropin-releasing hormone in normal and neoplastic corticotropes

Corticotropin-releasing hormone (CRH) plays an important role in regulating the development and function of hypothalamic-pituitary-adrenal axis. The m echanisms by which CRH regulates tissue-specific growth, differentiation an d gene expression remain to be established. In the present study, we show t hat CRH differentially regulates MAP kinase activity in normal ovine anteri or pituitary cells and mouse corticotrope AtT20 cells. Incubation of ovine normal anterior pituitary cells with CRH increased MAP kinase activity, an effect mimicked by cAMP and inhibited by the protein kinase A inhibitor H89 . In contrast, incubation of mouse pituitary tumor AtT20 cells with CRH inh ibited MAP kinase activity, an effect also mimicked by forskolin and inhibi ted by H89. This decrease in MAP kinase activity occurred with a time cours e similar to the increase seen in normal anterior pituitary cells. Furtherm ore, both effects of CRH on MAP kinase activity were inhibited by atrial na triuretic peptide (ANP). ANP also reversed the inhibition of DNA synthesis induced by CRH in AtT20 cells. Thus, CRH may differentially regulate cell g rowth in sheep normal anterior pituitary and mouse tumor corticotropes by m odulating MAP kinase activity through a mechanism dependent on cAMP product ion and subject to regulation by ANP. (C) 1998 Elsevier Science Ltd. All ri ghts reserved.