The mode of adrenocorticotrophin action in stimulating steroidogenesis: the obligatory role of adenosine 3′:5′-cyclic monophosphate and the involvement of rapidly-turning-over protein

Schulster, Dennis; Richardson, M. C.; Mackie, Caroline

doi:10.1042/bj1290008p

Cited by 6 publications

(1 citation statement)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several workers (Grahame-Smith et al, 1967;Schulster et al, 1972) have reported a 3min time-lag between the addition of ACTH and the onset of steroidogenesis. It has been suggested that this might be the time taken for synthesis ofa protein in response to ACTH, and there is some evidence that the time-lag may increase in the presence of submaximal doses of cycloheximide, which would be consistent with this hypothesis.…”

Section: Vol 142mentioning

confidence: 99%

Measurement of the dynamics of stimulation and inhibition of steroidogenesis in isolated rat adrenal cells by using column perfusion

Lowry¹,

McMartin²

1974

Biochemical Journal

View full text Add to dashboard Cite

Isolated adrenal cells were perfused in a small column by using Bio-Gel polyacrylamide beads as an inert supporting matrix, and the time-course of the response to various stimuli was observed by measuring fluorogenic 11-hydroxycorticosteroids in the effluent. A small but significant response was observed 1 min after stimulation with physiological concentrations of ACTH (adrenocorticotrophin), but the response did not start to build up rapidly for 3-4min and eventually reached a plateau after 9-10min. A similar pattern of events was observed for the decay of the steroid output on removal of ACTH. ACTH analogues, including one with a long duration of action in vivo, were found to produce responses with similar kinetics. However, cyclic AMP caused a more rapid increase in steroidogenesis and its effects were more short-lived after withdrawal. If, as present evidence suggests, cyclic AMP is produced rapidly after ACTH stimulation the delayed build-up of the steroidogenic response to ACTH would indicate that cyclic AMP may not be the intracellular mediator. When inhibitors were applied during ACTH stimulation, aminoglutethimide, which blocks mitochondrial conversion of cholesterol into pregnenolone (3beta-hydroxypregn-5-en-20-one), caused a rapid fall in steroid output (1 min), whereas cycloheximide took longer to achieve its full effect. Nevertheless, the response had fallen by 50% in 2 min, indicating a much shorter half-life than that previously reported for the labile protein implicated in steroidogenesis. In addition the rapid response to cyclic AMP makes it unlikely that steroid production is induced as a result of initiation of protein synthesis. This suggests that the labile protein plays an obligatory but permissive role in the development of the response. Column perfusion has proved to be a simple technique which can readily yield accurate data on responses of cells to stimulants and inhibitors.

show abstract

Section: Vol 142mentioning

confidence: 99%