Tissue-specific Regulation of Pituitary Proopiomelanocortin Gene Transcription by Corticotropin-releasing Hormone, 3',5'-cyclic Adenosine Monophosphate, and Glucocorticoids

The release of pituitary hormones derived from POMC is under multihormonal and tissue-specific control in the anterior and intermediate lobes of the pituitary where the same single-copy POMC gene is expressed. In order to assess the tissue-specificity of POMC regulation at the gene level, we have previously shown that glucocorticoids inhibit POMC gene transcription in the anterior but not in the intermediate pituitary. In the present work, we have investigated the role of corticotropin-releasing hormone (CRH) and cAMP in the differential regulation of anterior and intermediate pituitary POMC gene transcription. Using pituitary cells in primary culture and nuclear run-on transcription assays, we found that cAMP increases POMC gene transcription rate to the same extent in both anterior and intermediate pituitary cells while CRH only increases anterior pituitary POMC transcription rate. This observation contrasts with the stimulation of ACTH and alpha MSH release from anterior and intermediate pituitary cells, respectively, by both CRH and cAMP. In the anterior pituitary, both CRH and cAMP stimulated as well as basal POMC transcription rates are inhibited by glucocorticoids. In the anterior pituitary, both CRH stimulation and glucocorticoid inhibition of POMC transcription are rapid and do not require de novo protein synthesis. Thus, we report that transcription of the POMC gene is differentially regulated by CRH, cAMP, and glucocorticoids in anterior and intermediate pituitary tissues, in much the same way as the control of POMC processing and release.