Regulation of the biosynthesis of steroidogenic enzymes.
Recombinant DNA technology can permit study of the regulation of steroid hydroxylase gene expression at three levels. The first of these is cAMP-regulated gene expression. In the adrenal, ACTH, via cAMP, increases the expression of the genes for all of the cytochrome P-450 species involved in the steroid biosynthetic pathway, as well as the iron-sulfur protein, adrenodoxin. This action of cAMP is inhibited by cycloheximide, suggestive of the involvement of a regulatory protein factor in mediating this action of cAMP. The second level is tissue-specific regulation of steroid hydroxylase gene expression. An example of this which we have studied is the expression of cholesterol side-chain cleavage cytochrome P-450 (P-450sec) and 17 alpha-hydroxylase cytochrome P-450 (P-450(17) alpha) in the bovine ovary. P-450sec is expressed at high levels in the corpus luteum but at low levels in follicles, whereas P-450(17)alpha is expressed in follicles, but is undetectable in the corpus luteum. The third level is fetal imprinting. A number of the cytochrome P-450 species involving in the steroidogenic pathway are expressed in the fetal adrenal at a time when exposure of the gland to ACTH is very low, suggestive that factor(s) other than pituitary ACTH mediate this expression in fetal life.
Simpson
E R
ER
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Health Science Center, Dallas 75235-9051.
Mason
J I
JI
John
M E
ME
Zuber
M X
MX
Rodgers
R J
RJ
Waterman
M R
MR
D000311:Adrenal Glands / Q000187:drug effects / Q000196:embryology / Q000201:enzymology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D010053:Ovary / Q000201:enzymology; D013250:Steroid Hydroxylases / Q000235:genetics*
D000324:Adrenocorticotropic Hormone; D003577:Cytochrome P-450 Enzyme System; D000242:Cyclic AMP; D013250:Steroid Hydroxylases