Zona glomerulosa cells were isolated from the adult rat adrenal cortex and maintained in primary monolayer culture. The morphological and functional responses of the cells to different levels of potassium in the culture medium, and to serotonin, angiotensin II, ACTH and dibutyryl cyclic AMP were investigated. Medium containing 11 mM K* stimulated aldosterone biosynthesis during the first week of culture to levels up to 100 times greater than those observed with 6 mM K*, althoug h in both cases aldosterone production eventually declined to undetectable levels. Serotonin at 0.1 and 1.0 mM initially stimulated aldosterone biosynthesis, but to lower levels than those obtained with 11 mM K*. Angiotensi n II at 10 and 100 μg/ml did not stimulate aldosterone biosynthesis by cultured rat zona glomerulosa cells. ACTH at 100 mU/ml, and dibutyryl cyclic AMP at 0.5 mM, initially stimulated aldosterone biosynthesis but later depressed i t to below levels seen in their absence. Thus none of these trophic stimuli were found to be capable of maintaining aldosterone biosynthesis by cultured glomerulosa cells indefinitely. ACTH and dibutyryl cyclic AMP did, however, stimulate the corticosterone output of glomerulosa cells to steadily maintained levels similar to those obtained from ACTH-stimulated fasciculata-reticularis cells in culture. At the same time the mitochondrial cristae of the cultured cells changed from a tubular to a vesicular form in the presence of ACTH. This loss of glomerulosa-specific characteristics, with retention or acquisition of fasciculata-reticularis-like characteristics in the presence of ACTH or cyclic AMP, is discussed.
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