TY - JOUR
T1 - Regulation of expression of the genes encoding steroidogenic enzymes
AU - Simpson, Evan
AU - Lauber, Markus
AU - Demeter, Michelle
AU - Stirling, David
AU - Rodgers, Raymond
AU - Means, Gary
AU - Mahendroo, Mala
AU - Kilgore, Michael
AU - Mendelson, Carole
AU - Waterman, Michael
N1 - Funding Information:
Acknowledgements--This work was supported, in part, by USPHS Grants Nos HD 13234, DK28350, and AG08174, as well as by Grant No. 32.25326.88 from the Swiss National Foundation for Scientific Research. M.D., G.M. and M.M. were supported, in part, by USPHS Training Grant No. T32-HD07190. The authors gratefully acknowledge the expert editorial assistance of Sandra Finley.
PY - 1991
Y1 - 1991
N2 - In recent years it has become apparent that tropic hormones involved in steroidogenesis act to regualte 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), 17α-hydroxylase P450 (P45017α), 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 P45017α and P450SCC have been inserted upstream of the chloramphenicol acetyl transferase (CAT) and β-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 P45017α 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.
AB - In recent years it has become apparent that tropic hormones involved in steroidogenesis act to regualte 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), 17α-hydroxylase P450 (P45017α), 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 P45017α and P450SCC have been inserted upstream of the chloramphenicol acetyl transferase (CAT) and β-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 P45017α 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.
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U2 - 10.1016/0960-0760(91)90166-3
DO - 10.1016/0960-0760(91)90166-3
M3 - Article
C2 - 1958546
AN - SCOPUS:0025931845
SN - 0960-0760
VL - 40
SP - 45
EP - 52
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - 1-3
ER -