Modulation of steroidogenesis by selenium in a novel adrenal cell line developed using targeted tumorigenesis.
Glutathione peroxidase (GPx-1) is a selenoenzyme that metabolizes H(2)O(2), a source of potentially toxic free radicals. Steroidogenesis is markedly inhibited by H(2)O(2) in vitro.


OBJECTIVE
to study the effects of selenium deficiency on GPx activity and adrenal steroidogenesis in a novel adrenal cell line developed using targeted tumorigenesis.


METHODS
AN4Rppc7 cells were grown for 7 days in serum-free medium. 8-Br-cAMP-stimulated concentrations of steroid hormones were measured by RIA. StAR (Steroid Acute Reactive Protein) mRNA was measured by Northern blot.


RESULTS
selenium deficiency caused a 99% There was a 51%, progesterone, corticosterone and aldosterone production, respectively (p<0.05 by ANOVA). StAR mRNA was not affected by selenium.


CONCLUSIONS
selenium deficiency causes a marked decrease in GPx activity. Decreased steroid hormone production occurs for selenium concentrations equal or lower than 5 nM. The absence of changes in StAR mRNA content suggests that selenium deficiency does not affect cholesterol access to the mitochondria.
Chanoine
J P
JP
Department of Pediatrics, Endocrine and Diabetes Unit, University of British Columbia, Vancouver V5Z 4H4, BC, Canada. jchanoine@cw.bc.ca
Compagnone
N A
NA
Wong
A C
AC
Mellon
S H
SH
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D003345:Corticosterone / Q000096:biosynthesis; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012643:Selenium / Q000172:deficiency / Q000494:pharmacology*; D014158:Transcription, Genetic; D000094765:Glutathione Peroxidase GPX1; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000450:Aldosterone; D011374:Progesterone; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D012643:Selenium; D003345:Corticosterone; D000094765:Glutathione Peroxidase GPX1