Models to elucidate the regulation of adrenal cell death

Hypophysectomy-induced apoptosis in the rat adrenal gland is slow (not apparent until 12-24 h) and in-situ, 3'-end labeling (ISEL) of DNA strand breaks is restricted to a subpopulation of zona reticularis cells. In addition, it is completely blocked by ACTH. By contrast, apoptosis in the intact rat adrenal gland, cultured in the absence of trophic support, is extensive and rapid. Culture-triggered apoptosis (as determined by oligonucleosome formation) is attenuated by ACTH and is largely restricted to the zonae fasciculata and reticularis even at 3 h (as determined by ISEL and DAPI cytochemistry). Thus, this organ culture system may help elucidate factors that can acutely regulate adrenocortical cell survival. Quartered glands have a nearly 2-fold increase in oligonucleosome formation compared to intact glands at 3 h and are resistant to the antiapoptotic action of ACTH. In contrast, ACTH-induced corticosterone secretion is not attenuated. Angiotensin II (Ang II) enhances culture-triggered apoptosis, and its apoptotic action is attenuated by ACTH. These observations suggest that 1) acute hormonal modulation of apoptosis may require some level of gross adrenal structural integrity, and 2) ACTH and Ang II act in an antagonistic fashion to regulate adrenocortical apoptosis. The apoptotic effect of Ang II may be mediated via the type 2 receptor.