Expression of CYP27A, a gene encoding a vitamin D-25 hydroxylase in human liver and kidney

OBJECTIVEVitamin D-3 (D-3) is not active but must be hydroxylated at C-25 i n liver before acquiring its hormonal potential in the kidney. The sterol-2 7 hydroxylase (gene symbol: CYP27A) catalyses the oxidation of sterol side chain in bile acid synthesis but the enzyme is also known as a D-3-25 hydro xylase. DESIGN The study examined the expression of the gene encoding CYP27A in adu lt and fetal human livers and kidneys. SUBJECTS Thirty-nine adults (18 men and 21 women; mean age 58 years in men and 57 years in women) and three normal fetuses gestational age 17-19 weeks were studied. MEASUREMENTS Tissue CYP27A mRNA and serum 25OHD concentrations were measure d. RESULTS Normal specimens: CYP27A transcript was found to be higher in adult than in fetal livers but its expression was similar in adult and fetal kid neys. In fetuses, no difference was observed between CYP27A levels in liver s and kidneys. In adult livers CYP27A levels were higher in women than in m en. Hepatic CYP27A mRNA and serum 25OHD concentrations were both found to b e higher in summer than in winter. Multiple linear regression analyses indi cate that the season of the year and the serum 25OHD concentrations (but no t 1,25(OH)(2)D concentrations) are the best predictors of CYP27A mRNA abund ance in normal adult livers. In situ hybridization illustrates a clear labe l in hepatocytes which increases in intensity in the perivenous region of t he hepatic acinus. Pathological specimens: In one man with an hepatic carci noma there was a very large increase in CYP27A (> 1000 fold) compared to th e level found in the normal liver. In that patient, serum 25OHD concentrati ons were found to be high considering the level of CYP27A mRNA in the norma l hepatic area suggesting that the neoplastic tissue contributed to the C-2 5 hydroxylation of vitamin D. Specimens obtained from two patients sufferin g from focal hepatic hyperplasia indicate that in one case the level of CYP 27A mRNA was twice as high in the pathological than in the normal area whil e in the other its levels were similar in both areas. No difference in the CYP27A transcript was observed between specimens obtained from normal areas and those obtained form either an hepatic adenoma or from two intrahepatic colonic metastases. CONCLUSIONS CYP27A is present not only in the human adult liver but also in the adult kidney, and in the fetal liver and kidney. Our findings illustra te that CYP27A can be significantly upregulated in certain pathological sit uations such as in hepatic carcinoma and that the neoplastic tissue could c ontribute to the circulating concentration of 25OHD.