Regulation of expression of the genes encoding steroidogenic enzymes.

Simpson E, Lauber M, Demeter M, Stirling D, Rodgers R, Means G, Mahendroo M, Kilgore M, Mendelson C, Waterman M
J Steroid Biochem Mol Biol. 1991 40 (1-3): 45-52

PMID: 1958546 · DOI:10.1016/0960-0760(91)90166-3

In recent years it has become apparent that tropic hormones involved in steroidogenesis act to regulate the expression of the enzymes involved in the various steroidogenic pathways. This is particularly evident in the ovary where the episodic secretion of steroids throughout the ovarian cycle is regulated largely by changes in the levels of the particular enzymes involved in each step of the steroid biosynthetic pathways. Recently, the genes for the various cytochrome P450 species involved in ovarian steroidogenesis, namely cholesterol side-chain cleavage P450 (P450SCC), 17 alpha-hydroxylase P450 (P450(17 alpha], and aromatase cytochrome P450 (P450AROM) have been isolated and characterized, making it possible to study the regulation of expression at the molecular level. To this end, a series of chimeric constructs have been prepared in which fragments of the 5'-untranslated region of bovine P450(17 alpha) and P450SCC have been inserted upstream of the chloramphenicol acetyl transferase (CAT) and beta-globin reporter genes. These constructs have been used to transfect primary cultures of bovine luteal and thecal cells. The results indicate that cAMP responsiveness lies within defined regions of genes which do not contain a classical CRE, similar to previous results utilizing adrenal cells in culture. Furthermore, although constructs containing both the P450(17 alpha) and P450SCC 5'-upstream regions are expressed in both luteal and thecal cell cultures, only those containing the P450SCC sequences are expressed in luteal cells. Studies on the expression of P450AROM indicate that the promoter which is responsible for its expression in human placenta is not operative in the corpus luteum. Thus estrogen biosynthesis may be regulated by the differential use of tissue specific promoters, thus accounting for the complexity and multifactorial nature of the expression of this activity.

MeSH Terms (19)

Animals Aromatase Base Sequence Blotting, Northern Blotting, Western Cattle Chloramphenicol O-Acetyltransferase Cholesterol Side-Chain Cleavage Enzyme Exons Female Gene Expression Regulation, Enzymologic Genome, Human Globins Humans Molecular Sequence Data Ovary RNA, Messenger Steroid 17-alpha-Hydroxylase Steroids

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