CHANGES IN ADRENOCORTICOTROPIC HORMONE (ACTH) RELEASE FROM THE CULTURED ANTERIOR-PITUITARY-CELLS OF STREPTOZOTOCIN-INDUCED DIABETIC RATS

We examined ACTH release from cultured anterior pituitary cells of str eptozotocin (STZ)-induced diabetic rats. Rats 1 week after the injecti on of STZ (55 mg/kg, i.v.) were used as a short-term diabetic model, w hile rats 8 weeks after the injection of STZ were used as a long-term diabetic model. ACTH release induced by corticotropin-releasing factor s (CRF) was significantly increased in the short-term diabetic rats, w hereas ACTH release decreased in the long-term diabetic rats, A stimul ator of adenylate cyclase, forskolin, caused marked increases in ACTH release in short-term diabetic rats, whereas it did not affect the lon g-term diabetic rats. An L-type Ca2+ channel agonist, BAY K 8644, did not affect ACTH release in the short-term diabetic rats, although it d ecreased ACTH release in long-term diabetic rats. In addition, CRF-ind uced ACTH release also increased in normal anterior pituitary cells cu ltured under high glucose conditions (25 mmol/l) for 5 d. These result s suggest that the increase in the CRF-induced ACTH release from cultu red anterior pituitary cells of short-term diabetic rats appears to in volve the cAMP system in part, In contrast, the decrease in the CRF-in duced ACTH release from the cultured anterior pituitary cells of long- term diabetic rats may indicate a change in the properties of the L-ty pe Ca2+ channel coupled with the CRF receptor, or in the CRF receptor itself.