Effects of corticotrophin-releasing factor and arginine-vasopressin on proopiomelanocortin (POMC) mRNA levels, release and storage of adrenocorticotrophin from mouse anterior pituitary cells.

1. The present studies were undertaken to determine the effects of arginine vasopressin (AVP), corticotrophin-releasing factor (CRF) and AVP in combination with CRF on proopiomelanocortin (POMC) gene expression, and in the release and biosynthesis of POMC products (i.e. ACTH). 2. After a 3 hr treatment, AVP (10(-7) M), CRF (10(-7) M) and AVP (10(-7) M) in combination with CRF (10(-7) M) stimulated ACTH release by 291 +/- 19.2%, 377.4 +/- 25.6% and 462.1 +/- 38.4% (P < 0.01), respectively, with respect to basal secretion; while ACTH content diminished by 84.0 +/- 4.6%, 81.3 +/- 2.1% and 71.0 +/- 1.5% (P < 0.01), respectively, with respect to basal. Total POMC mRNA levels were not affected after a 3 hr treatment. 3. When cells were treated with a wide range of AVP concentrations (10(-11)-10(-7) M) to which we added different concentrations of CRF, modulation of AVP-induced ACTH release was most effective at CRF concentrations of < 10(-10) M. 4. Prolonged (3-6 hr) exposure to as low as 10(-10) M CRF or 10(-9) M AVP resulted in homologous desensitization of ACTH secretion. However, these pretreated cells were able to respond to a further challenge of CRF and AVP. This paper provides new information on the dose ranges over which desensitization and cross-sensitization between CRF and AVP secretory effects take place in mouse anterior pituitary cells.