Cyclic AMP-induced expression of steroidogenic acute regulatory protein is dependent upon phosphoprotein phosphatase activities.
In addition to the well-documented role of protein kinases in the regulation of steroid production, phosphoprotein phosphatase (PP) activity is required for steroidogenesis. In the present study, we have used the mouse Y1 adrenocortical cell line to identify the site of action of PPs on steroid production by measuring the effects of PP inhibition on the expression of the steroidogenic acute regulatory (StAR) protein and on steroid production. Forskolin-induced activation of cyclic AMP-dependent protein kinase (PKA) enhanced steroidogenesis and this was accompanied by an increased expression of StAR protein. Both steroidogenesis and StAR protein expression were inhibited by two structurally dissimilar inhibitors of PP1 and PP2A activities, okadaic acid and calyculin A. These results suggest that inhibition of PP1 and PP2A inhibits steroid production by preventing the expression of the StAR protein, implicating PP1/2A dephosphorylation reactions as important regulators of stimulus-dependent StAR protein expression, and thus of steroidogenesis.
Jones
P M
PM
Endocrinology and Reproduction Research Group, School of Biomedical Sciences, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK. peter.jones@kcl.ac.uk
Sayed
S B
SB
Persaud
S J
SJ
Burns
C J
CJ
Gyles
S
S
Whitehouse
B J
BJ
D000302:Adrenal Cortex / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008387:Marine Toxins; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D011284:Pregnenolone / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein
D004791:Enzyme Inhibitors; D006888:Hydroxycholesterols; D007527:Isoenzymes; D008387:Marine Toxins; D010080:Oxazoles; D010750:Phosphoproteins; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; C003585:22-hydroxycholesterol; D005576:Colforsin; D019319:Okadaic Acid; D011374:Progesterone; D011284:Pregnenolone; C059041:calyculin A; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017027:Protein Tyrosine Phosphatases