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 streptozotocin (STZ)-induced diabetic rats. Rats 1 week after the injection of STZ (55 mg/kg, i.v.) were used as a short-term diabetic model, while rats 8 weeks after the injection of STZ were used as a long-term diabetic model. ACTH release induced by corticotropin-releasing factors (CRF) was significantly increased in the short-term diabetic rats, whereas ACTH release decreased in the long-term diabetic rats, A stimulator of adenylate cyclase, forskolin, caused marked increases in ACTH release in short-term diabetic rats, whereas it did not affect the long-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 decreased ACTH release in long-term diabetic rats. In addition, CRF-induced ACTH release also increased in normal anterior pituitary cells cultured under high glucose conditions (25 mmol/l) for 5 d. These results suggest that the increase in the CRF-induced ACTH release from cultured anterior pituitary cells of short-term diabetic rats appears to involve the cAMP system in part, In contrast, the decrease in the CRF-induced ACTH release from the cultured anterior pituitary cells of long-term diabetic rats may indicate a change in the properties of the L-type Ca2+ channel coupled with the CRF receptor, or in the CRF receptor itself.