Apoptotic cell death in the rat adrenal gland: an in vivo and in vitro investigation

Abstract

Adrenocortical cell apoptosis was studied by using an established in vivo model, the hypophysectomized rat, and an in vitro model, viz., rat adrenal glands in short-term organ culture. In vivo, apoptosis (biochemical autoradiographic analysis of internucleosomal DNA cleavage) was weak and not apparent until 12-24 h after hypophysectomy. In situ histochemical localization of 3'-end DNA strand breaks revealed that apoptosis in vivo occurred nearly exclusively in subpopulations of zona reticularis cells. Adrenocorticotropic hormone (ACTH) maintenance completely blocked these indices of apoptosis. By contrast, apoptosis (DNA fragmentation) in cultured rat adrenal glands without ACTH was extensive and relatively rapid, being apparent after 1 h and increasing with the duration of incubation. ACTH attenuated (by 44%) but did not completely block apoptosis in vitro. Thus, ACTH appears to be the sole pituitary hormone that forestalls apoptosis of terminally differentiated adrenocortical (zona reticularis) cells. However, the discrepancy between in vitro and in vivo models in terms of the magnitude and rate of DNA fragmentation suggests that, in vivo, other factors finely regulate the magnitude of adrenocortical apoptotic cell death.

Synthetic modified N-POMC1–28 controls in vivo proliferation and blocks apoptosis in rat adrenal cortex

“…In addition, the evidence for the remodeling of the vasculature after hypophysectomy reinforces the observation that POMC peptides are also required for the maintenance of adult cortical vasculature (Thomas et al 2003). Finally, in contrast to the results of short-term adrenal culture (Carsia et al 1996), the susceptibility of the ZG to triggered cell death is similar to that of other regions. The anti-apoptotic action of ACTH is expected, but the efficiency of the synthetic N-POMC 1-28 is noteworthy.…”

Transition from organogenesis to stem cell maintenance in the mouse adrenal cortex

“…10,18,19 Nevertheless, it is still not clear whether (1) the adult adrenocortical zones are maintained by independent proliferation of cells within a zone, (2) the ZG and ZF/ZR are maintained separately by stem cells located at the border between the ZG and ZF (ZI/ZU in the rat), or (3) the entire cortex is maintained by centripetal migration of cells from a peripheral stem cell population located either within the capsule, or the subcapsular region of the ZG. 20,21 A recent study has suggested a variant of the third possibility involving two populations of embryonic adrenocortical progenitors, both of which are capable of generating all the steroidogenic cell types in the adrenal cortex.…”

Target cells for cytochrome P450-catalysed irreversible binding of 7,12-dimethylbenz[a]anthracene (DMBA) in rodent adrenal glands

“…DMBA-induced apoptosis has recently been observed in rat adrenal zona reticularis (Tsuta et al 2001), and also in pre-B cells cocultured with bone marrow stromal cells from AhR-null mice (but not from CYP1B1-null mice), indicating a need for CYP1B1 (Heidl et al 1999). Cells undergoing spontaneous apoptosis are found mainly in the zona reticularis of rat (Wyllie et al 1973;Zajicek et al 1986;Carsia et al 1996;Mitani et al 1999;Tsuta et al 2001). Given the fact that adrenal CYP1B1 is induced both by the AhR-agonist PCB 126 (Pang et al 1999) and by ACTH (Brake et al 1999), focal CYP1B1-catalysed DMBA binding in the zona reticularis may therefore occur in cells programmed to undergo apoptosis (Nebert et al 2000).…”