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Abstract: Prolactin regulatory element-binding (PREB) protein is a transcription factor not only in pituitary but also adrenal gland. Steroid 11β-hydroxylase (CYP11B1), a member of the cytochrome p-450 superfamily, is responsible for the last step of glucocorticoid biosynthesis in the adrenal cortices of many kinds of animals. In the present study, we have examined the role of PREB in regulating CYP11B1. CYP11B1 expression was found to be regulated by cAMP, which stimulated the expression of PREB. In addition, PREB induced the expression of the luciferase reporter protein that was under the control of the CYP11B1 promoter. Electrophoretic mobility shift analysis (EMSA) showed that PREB mediates its transcriptional effect by binding to the PREB-responsive cis-element (PRCE) of the CYP11B1 promoter. The knockdown of PREB expression attenuated the effects of cAMP on CYP11B1 expression. In summary, our data showed that in the adrenal gland, PREB regulates the transcription of the CYP11B1 gene via cAMP. [Copyright &y& Elsevier]

Abstract: The entry of cholesterol contained within high-density lipoprotein (HDL) into adrenocortical cells is mediated by a human homologue of SR-BI, CD36, and LIMPII Analogous-1 (CLA-1) and thus augmenting their growth. To address the role of CLA-1, we created a mutant mCLA that lacked the C-terminal tail. HDL CE selective uptake by cells carrying the mCLA-1 receptor was fully active and equivalent to those transfected with full-length CLA-1 (fCLA-1). Expression of mCLA inhibited the proliferation of an adrenocortical cell line and the incorporation of [3H]thymidine into the cells. This effect was sensitive to wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). Our transcriptional studies revealed that the inhibitory action of mCLA required the transcriptional factor AP-1 and the effect of HDL on AP-1 activation was also abrogated by wortmannin. These findings raise the possibility that the inhibitors of the effects of HDL may be of therapeutic value for adrenocortical tumor. [Copyright &y& Elsevier]