title: CYP21A2 expression is localized in the developing distal epithelium of the human perinatal lung and is compatible with in situ production and intracrine actions of active glucocorticoids.
abstract: Glucocorticoids play essential roles in lung development. We investigated for expression of CYP21A2 (21-hydroxylase) as well as for the presence of the corresponding protein and identification of CYP21A2-expressing cells in several human developing lungs. Expression of some related genes was also assessed. CYP21A2 and CYP17A1 (P450c17) mRNAs were found in all the 34 lung samples from 17 to 40 weeks' gestation at variable levels. No correlation was found according to sex but a correlation with age was detected for CYP17A1 only. In contrast, CYP11B1 (11β-hydroxylase)- and CYP11B2 (aldosterone synthase)-mRNAs were not detected. Significant levels of the CYP21A2 protein were detected in all the analyzed samples, while only very low signals were detected for CYP17A1 protein. In situ hybridization revealed that CYP21A2 was almost exclusively expressed in the distal epithelium. It was reported that the lung distal epithelium of human fetuses also express 11β-hydroxysteroid dehydrogenase type 2, which catalyzes cortisol inactivation into cortisone. Based on this information, intracrine glucocorticoid actions should take place from CYP21A2 products through the glucocorticoid receptor in the absence of cortisol. In contrast, mineralocorticoid receptor activation did not seem to depend on deoxycorticosterone produced from local activity of CYP21A2 because of the reported circulating amounts of aldosterone.
authors.affiliation: Reproduction, Mother and Youth Health, Centre de recherche CHU de Québec, Québec, QC, Canada; Centre de Recherche en Biologie de la Reproduction (CRBR), Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Wafae
authors.initials: W
authors.lastname: Bouhaddioui
authors.affiliation: Reproduction, Mother and Youth Health, Centre de recherche CHU de Québec, Québec, QC, Canada; Department of Obstetrics/Gynecology & Reproduction, Faculty of Medicine, Université Laval, Québec, QC, Canada; Centre de Recherche en Biologie de la Reproduction (CRBR), Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Provost
authors.affiliation: Reproduction, Mother and Youth Health, Centre de recherche CHU de Québec, Québec, QC, Canada; Department of Obstetrics/Gynecology & Reproduction, Faculty of Medicine, Université Laval, Québec, QC, Canada; Centre de Recherche en Biologie de la Reproduction (CRBR), Faculté de Médecine, Université Laval, Québec, QC, Canada. Electronic address: yves.tremblay@crchudequebec.ulaval.ca.
authors.forename: Yves
authors.initials: Y
authors.lastname: Tremblay
mesh_terms: D000367:Age Factors; D000450:Aldosterone / Q000378:metabolism; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D003900:Desoxycorticosterone / Q000378:metabolism; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008168:Lung / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000254:growth & development / Q000378:metabolism*; D012737:Sex Factors; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D013255:Steroid 21-Hydroxylase / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D003900:Desoxycorticosterone; D000450:Aldosterone; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D006854:Hydrocortisone
keywords: 11-Deoxycortisol; 21-Hydroxylase; Deoxycorticosterone; Glucocorticoids; Lung development; Mineralocorticoids; Respiratory distress syndrome