A link between lung androgen metabolism and the emergence of mature epithelial type II cells.
Lung maturation is delayed in male fetuses compared with female fetuses, which has been attributed to higher levels of androgens in the male lung. Our previous studies demonstrated that the genes encoding for the 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) type 5 (androstenedione --> testosterone) and type 2 (the opposite reaction) are expressed in human epithelial type II (PTII)-like A549 cells and in human lung fibroblasts, respectively. Here, we aim to explain the physiological relevance of androgen synthesis by PTII cells. We showed that both 17 beta-HSD type 2 and type 5 genes are upregulated in correlation with the emergence of mature PTII cells in both male and female developing lungs of the mouse. In contrast, the androgen receptor gene is expressed equally in both sexes with no temporal regulation. We conclude that the expression profile of the 17 beta-HSD type 5 gene does not explain the presence of higher levels of androgen in the male fetal lung, but that androgen synthesis must be a normal feature of mature PTII cells for both sexes. The production of androgens after the emergence of mature PTII cells should negatively regulate PTII cell maturation and, thus, a role for androgens in cell reprogramming is suggested.
Provost
Pierre R
PR
Laboratory of Ontogeny and Reproduction, Department of Obstetrics and Gynecology, and Centre de Recherche en Biologie de la Reproduction, Faculty of Medicine, Laval University, Quebec, Quebec, Canada.
Simard
Marc
M
Tremblay
Yves
Y
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000728:Androgens / Q000235:genetics / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D002384:Catalysis; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins; D008168:Lung / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C; D012737:Sex Factors; D013739:Testosterone / Q000096:biosynthesis
D000728:Androgens; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D037721:Pulmonary Surfactant-Associated Protein C; C489679:SFTPC protein, human; C489680:Sftpc protein, mouse; D013739:Testosterone; D000735:Androstenedione; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase