This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Provost, P. R. Articles by Tremblay, Y. Search for Related Content PubMed PubMed Citation Articles by Provost, P. R. Articles by Tremblay, Y.

Androgen Inactivation in Human Lung Fibroblasts: Variations in Levels of 17ß-Hydroxysteroid Dehydrogenase Type 2 and 5-Reductase Activity Compatible with Androgen Inactivation

Laboratories of Ontogeny and Reproduction (P.R.P., R.D., N.F., Y.T.), Centre Hospitalier Unìversitaire de Québec, Pavillon Centre Hospitalier de l’Université Laval, Québec, Canada G1V 4G2; Department of Obstetrics and Gynecology (C.H.B.), HealthPartners Regions Hospital, St. Paul, Minnesota 55101; and Department of Obstetrics and Gynecology and Centre de Recherche en Biologie de la Reproduction (Y.T.), Faculty of Medicine, Laval University, Québec, Canada G1V 4G2

Address all correspondence and requests for reprints to: Dr. Yves Tremblay, Laboratory of Ontogeny and Reproduction, Room T-1–58, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, 2705 Laurier Boulevard, Québec, Canada G1V 4G2. E-mail: . yves.tremblay{at}crchul.ulaval.ca

Abstract

Androgens delay lung maturation through their action on lung fibroblasts. Knowing that testosterone is secreted by the lung epithelial-like cell line A-549, we have studied the metabolism of androgens by several human lung diploid fibroblasts cell lines. No 17-ketosteroid reductase activity was detected. In contrast, testosterone was transformed mainly into androstenedione and androstanedione with no 5-dihydrotestosterone formed, indicating the presence of 17ß- hydroxysteroid dehydrogenase (HSD) type 2 and 5-reductase activities. The eight cell lines analyzed had either a low or high 17ß-HSD type 2 activity level. No correlation between these levels and the sex or age stage of cells was established, but Northern blot analysis of human lung RNA samples of five adult subjects revealed very similar variations between subjects in the level of 17ß-HSD type 2 mRNA. The 5-reductase activity had a marked substrate preference for androstenedione, the product of 17ß-HSD type 2. When tritiated testosterone was used as substrate, only barely detectable levels of 5-dihydrotestosterone were observed by HPLC in the presence of the 17ß-HSD type 2 inhibitor EM-919. The use of unlabeled testosterone or of the antiandrogen hydroxyflutamide demonstrated that the tritiated testosterone substrate itself had no effect on levels of 5-reduction. In fact, in these cells, 5-reductase has no significant activity on testosterone, but it further converts the product of 17ß-HSD type 2, thus playing a role with 17ß-HSD type 2 in androgen inactivation. Because androgens delay lung maturation and surfactant synthesis by their action on lung fibroblasts, it is of particular interest to find that the steroid metabolism of these lung fibroblast cells is oriented toward androgen inactivation. Because lung fibroblasts of subjects with low 17ß-HSD type 2 expression levels are likely to be exposed to higher levels of androgens, an allelic variation of the 17ß-HSD-2 gene is suspected, which would result in familial incidence of respiratory distress. This is in line with reported cases of familial incidence of respiratory distress.

This article has been cited by other articles:

				P. R Provost, E. Boucher, and Y. Tremblay Apolipoprotein A-I, A-II, C-II, and H expression in the developing lung and sex difference in surfactant lipids J. Endocrinol., March 1, 2009; 200(3): 321 - 330. [Abstract] [Full Text] [PDF]

				M. A. Carey, J. W. Card, J. W. Voltz, D. R. Germolec, K. S. Korach, and D. C. Zeldin The impact of sex and sex hormones on lung physiology and disease: lessons from animal studies Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L272 - L278. [Abstract] [Full Text] [PDF]

				M. C. Henson and V. D. Castracane Leptin in Pregnancy: An Update Biol Reprod, February 1, 2006; 74(2): 218 - 229. [Abstract] [Full Text] [PDF]

				G. Pelletier, V. Luu-The, S. Li, and F. Labrie Localization of Type 8 17{beta}-hydroxysteroid Dehydrogenase mRNA in Mouse Tissues as Studied by In Situ Hybridization J. Histochem. Cytochem., October 1, 2005; 53(10): 1257 - 1271. [Abstract] [Full Text] [PDF]

				P. R. Provost, M. Simard, and Y. Tremblay A Link between Lung Androgen Metabolism and the Emergence of Mature Epithelial Type II Cells Am. J. Respir. Crit. Care Med., August 1, 2004; 170(3): 296 - 305. [Abstract] [Full Text] [PDF]

				M C Henson, K F Swan, D E Edwards, G W Hoyle, J Purcell, and V D Castracane Leptin receptor expression in fetal lung increases in late gestation in the baboon: a model for human pregnancy Reproduction, January 1, 2004; 127(1): 87 - 94. [Abstract] [Full Text] [PDF]