Rat adrenal glomerulosa and fasciculata-reticularis cell sensitivity to comparable molar doses of angiotensin II (AII) (2.4 X 10(-12) to 2.4 X 10(-4) M) and ACTH (alpha-1-24-adrenocorticotropin) (3.5 X 10(-13) to 3.5 X 10(-8) M) as well as small increments in potassium (K+) (3.7 to 13 meq/liter) was investigated. Glomerulose cells responded to physiological levels of AII (2.4 X 10(-10) M) and alpha-1-24-ACTH (3.5 X 10(-12) M), whereas an increment of as little 0.3 meq/liter in medium K+ also significantly increased aldosterone production. Of the three stimuli, alpha-1-24-ACTH caused the greatest aldosterone rise (11 times control). Fasciculata-reticularis cells responded only to alpha-1-24-ACTH. Whereas the threshold sensitivity was no lower than with glomerulosa cells, the maximum response was significantly greater (63 times control). These findings are consistent with findings documented in vivo in man, suggesting that the control of aldosterone secretion is similar in these two species.
The present study compares changes in cytosolic calcium and steroidogenesis when rat adrenal cells are stimulated with potassium (K+), angiotensin II (AII), ACTH, and (Bu)2cAMP (cAMP). The calcium-sensitive fluorescent dye, quin 2, was used to determine cytosolic calcium concentrations. K+ and AII both induced parallel increases in cytosolic calcium and aldosterone output. Removal of external calcium from the incubation media or addition of nifedipine inhibited the rise in cytosolic calcium in response to these two secretagogues. Inhibition of release of intracellularly-bound calcium by incubating the cells with 8-(N-N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride or dantrolene sodium reduced the rise in cytosolic calcium in response to these two secretagogues by 40-50%. In contrast, neither ACTH nor cAMP altered cytosolic calcium levels in the glomerulosa cells, even though quin 2-loaded cells showed a normal steroidogenic response to these agents. Thus, there was a dissociation between the cytosolic calcium response and steroidogenesis during cAMP stimulation of glomerulosa cells. Fasciculata cells incubated in the presence of increasing concentrations of cAMP, ACTH, K+, or AII failed to demonstrate an increase in cytosolic calcium, although the cells had a normal steroidogenic response to ACTH and cAMP. These results suggest that the responses of fasciculata and glomerulosa cells to secretagogues have different dependencies on calcium. The fasciculata cell has little calcium dependency while the glomerulosa cell has a variable dependency. In the glomerulosa cell, both AII and K+ induced similar responses in steroid output and cytosolic calcium, suggesting an important role for cytosolic calcium as a mediator of the steroidogenic effect of these secretagogues. Furthermore, part of the increase in cytosolic calcium induced by these agents is due to release of intracellularly bound calcium and part from increased calcium flux across the cell membrane. The absence of such dependency with cAMP suggests that an increase in intracellular calcium levels is not required for increased steroidogenesis in glomerulosa cells.
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