title: 17Beta-HSD type 5 expression and the emergence of differentiated epithelial Type II cells in fetal lung: a novel role for androgen during the surge of surfactant.
abstract: Lung maturation is delayed in male fetuses compared to female fetuses. This has been attributed to higher levels of androgens in the male lung. We previously showed that the genes encoding for the 17beta-hydroxysteroid dehydrogenase (HSD) type 5 (conversion of androstenedione in testosterone) and type 2 (the opposite reaction) are, respectively, expressed in the human epithelial Type II (PTII)-like A549 cells and in human lung fibroblasts. Here, we aim to explain the physiological relevance of androgen synthesis by PTII cells. We showed that 17beta-HSD type 2 and type 5 genes are both up-regulated in correlation with the emergence of mature PTII cells in both male and female developing lungs of the fetal mouse. In contrast, the androgen receptor gene is expressed at similar levels in both sexes with no temporal regulation. In conclusion, the expression profile of the 17beta-HSD type 5 gene does not explain the presence of higher levels of androgens in the male fetal lung but that androgen synthesis must be a normal characteristic 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 novel and normal role for androgens in cell reprogramming is proposed.
authors.affiliation: Laboratory of Ontogeny and Reproduction, Laval University Medical Center, Centre de Recherche en Biologie de la Reproduction (CRBR), Department of Obstetrics and Gynecology, Laval University, Que., Canada G1V 4G2. yves.tremblay@crchul.ulaval.ca
authors.forename: Yves
authors.initials: Y
authors.lastname: Tremblay
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Provost
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases; D000728:Androgens / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D004960:Estradiol Dehydrogenases / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins; D008168:Lung / Q000254:growth & development*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000235:genetics; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics; D012737:Sex Factors; D015854:Up-Regulation
chemical_list: D000728:Androgens; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; D011944:Receptors, Androgen; C489680:Sftpc protein, mouse; D015067:17-Hydroxysteroid Dehydrogenases; C032690:3-alpha-(17-beta)-hydroxysteroid dehydrogenase (NAD(+)); C510576:Akr1c6 protein, mouse; D004960:Estradiol Dehydrogenases