Nucleic Acids Research, Vol 26, Issue 9 2173-2178, Copyright © 1998 by Oxford University Press
A Subramanian, J Wang and G Gil
The level of expression of a number of sexually differentiated liver
proteins is primarily determined by plasma growth hormone (GH). Adult males
have a pulsatile profile of GH release, while females have a relatively
steady-state pattern of GH release. An important subset of these sexually
differentiated hepatic proteins is certain cytochrome P450s (P450s).
CYP3A10/6beta-hydroxylase is a male-specific P450 that catalyzes
6beta-hydroxylation of lithocholic acid, and the pattern of GH secretion is
directly responsible for male-specific expression of this gene. The DNA
element involved in GH-mediated regulation of CYP3A10/6beta-hydroxylase
promoter activity binds a member of the STAT (signal transducers and
activators of transcription) family of proteins. In this study we
functionally demonstrate that two members of the STAT family, STAT 5a and
STAT 5b, mediate GH-dependent regulation of CYP3A10/6beta-hydroxylase
promoter activity. Furthermore, a neighboring DNA element binds NF-Y, a
transcription factor involved in maintaining high levels of transcription
of many genes and known to functionally interact with other factors. In the
CYP3A10/6beta- hydroxylase gene, NF-Y also modulates binding of STAT 5,
thereby modulating GH-mediated activation of its transcription.
ARTICLES
STAT 5 and NF-Y are involved in expression and growth hormone-mediated sexually dimorphic regulation of cytochrome P450 3A10/lithocholic acid 6beta-hydroxylase
Department of Biochemistry and Molecular Biophysics, Medical College of Virginia, PO Box 980614, Richmond, VA 23298-0614, USA.
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