Diminished adrenal steroidogenic activity in aging rats: new evidence from adrenal cells cultured from young and aged normal and hypoxic animals

Adrenal cells from 2-6-month-old young rats (Y cells) and from 19-25-month-old aged male rats (O cells) were adapted to primary monolayer culture. The cultures of Y and O cells appeared to be primarily epithelial and rounded up in response to stimulation with adrenocorticotropic hormone (ACTH). The general morphology of O cells was comparable to that observed in Y cells except for the presence of lipofuscin-like granules, a cellular marker of aging, in O cells, but not in Y cells. ACTH-stimulated steroid production by O cells was 52% lower than that by Y cells. Exposure of intact young rats to hypoxia (0.5 atmosphere) for 21 days prior to sacrifice and culture resulted in a 122% increase of ACTH-stimulated adrenal steroidogenic activity in the cultured cells, but this effect was not observed in adrenal cells cultured from hypoxic aged rats. The results suggest that there is an age-related diminution in rat adrenal steroidogenic capacity in response to ACTH stimulation in culture derived from Y and O animals; hypoxic stress magnifies this difference.