title: Phosphoprotein phosphatases regulate steroidogenesis by influencing StAR gene transcription.
abstract: The rate-limiting step in steroidogenesis is the transport of cholesterol into the mitochondria, and this is controlled by the steroidogenic acute regulatory (StAR) protein. We have previously shown that inhibition of phosphoprotein phosphatase 1 and 2A (PP1/2A) activities with the PP1/2A inhibitor calyculin A selectively reduces StAR protein expression and thus inhibits the synthesis of steroid hormones. The aim of this study was to determine whether this inhibition of StAR protein expression occurs at the level of transcription of StAR mRNA. We have used a competitive reverse transcription-polymerase chain reaction (RT-PCR) technique to determine whether inhibition of PP1/2A activities has any effect on the levels of StAR mRNA. Exposure of Y1 cells to forskolin significantly increased the expression of StAR mRNA and this forskolin-induced increase was reduced after exposure to Cal A at levels similar to those seen in the controls. These results suggest that cyclic AMP-induced increases in StAR mRNA levels are dependent upon phosphoprotein phosphatase activities.
authors.affiliation: Endocrinology and Reproduction Research Group, Guy's, King's & St. Thomas' School of Biomedical Sciences, Guy's Campus, London Bridge, London, SE1 9RT, United Kingdom. chris.burns@kcl.ac.uk
authors.forename: C J
authors.initials: CJ
authors.lastname: Burns
authors.forename: S L
authors.initials: SL
authors.lastname: Gyles
authors.forename: S J
authors.initials: SJ
authors.lastname: Persaud
authors.forename: D
authors.initials: D
authors.lastname: Sugden
authors.forename: B J
authors.initials: BJ
authors.lastname: Whitehouse
authors.forename: P M
authors.initials: PM
authors.lastname: Jones
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D008387:Marine Toxins; D051379:Mice; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics*; D011284:Pregnenolone / Q000378:metabolism; D054645:Protein Phosphatase 1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000096:biosynthesis* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D008387:Marine Toxins; D010080:Oxazoles; D010750:Phosphoproteins; D012333:RNA, Messenger; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; D005576:Colforsin; D011284:Pregnenolone; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1