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Levels of Dihydrotestosterone, Testosterone, Androstenedione, and Estradiol in Canalicular, Saccular, and Alveolar Mouse Lungs

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Abstract

Androgens and estrogens are known regulators of fetal and postnatal lung development, but their levels in the developing lung have never been determined. We present here, for the first time, a gas chromatography-mass spectrometry (GC/MS) quantification of dihydrotestosterone, testosterone, androstenedione, and estradiol in canalicular, saccular, and alveolar stage lungs of both sexes. Testosterone, androstenedione, and estradiol were observed in all the analyzed lung samples from gestation day (GD) 16.5 to postnatal day (PN) 30, totalizing 383 individual mice. Levels of these three steroids decreased between birth and PN 5. In contrast, dihydrotestosterone was detected only in male samples on GD 19.5, PN 0, and PN 30. A significant sex difference was observed for testosterone and androstenedione but not for estradiol. Steroid levels were also determined in skinned hind legs for comparison. Three-way analysis of variance revealed that tissue (lung or leg) had a significant effect on testosterone levels for both sexes, but not on androstenedione and estradiol levels. Low but significant testosterone and androstenedione levels were observed in all the females and in prepubertal male samples. These levels must be sufficient to induce androgen receptor activation, as suggested by our recent report showing the presence of androgen receptor in the nucleus of several lung cells in corresponding developmental ages and sexes.

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References

  1. Carey MA, Card JW, Voltz JW, Germolec DR, Korach KS, Zeldin DC (2007) The impact of sex and sex hormones on lung physiology and disease: lessons from animal studies. Am J Physiol Lung Cell Mol Physiol 293:L272–L278

    Article  CAS  PubMed  Google Scholar 

  2. Nielsen HC, Zinman HM, Torday JS (1982) Dihydrotestosterone inhibits fetal rabbit pulmonary surfactant production. J Clin Invest 69:611–616

    Article  CAS  PubMed  Google Scholar 

  3. Rodriguez A, Viscardi RM, Torday JS (2001) Fetal androgen exposure inhibits fetal rat lung fibroblast lipid uptake and release. Exp Lung Res 27:13–24

    Article  CAS  PubMed  Google Scholar 

  4. Kimura Y, Suzuki T, Kaneko C, Darnel AD, Akahira J, Ebina M, Nukiwa T, Sasano H (2003) Expression of androgen receptor and 5alpha-reductase types 1 and 2 in early gestation fetal lung: a possible correlation with branching morphogenesis. Clin Sci (Lond) 105:709–713

    Article  CAS  Google Scholar 

  5. Levesque BM, Vosatka RJ, Nielsen HC (2000) Dihydrotestosterone stimulates branching morphogenesis, cell proliferation, and programmed cell death in mouse embryonic lung explants. Pediatr Res 47:481–491

    Article  CAS  PubMed  Google Scholar 

  6. Adamson IY, Bakowska J, McMillan E, King GM (1990) Accelerated fetal lung maturation by estrogen is associated with an epithelial-fibroblast interaction. In Vitro Cell Dev Biol 26:784–790

    Article  CAS  PubMed  Google Scholar 

  7. Chu AJ, Rooney SA (1985) Estrogen stimulation of surfactant synthesis. Pediatr Pulmonol 1:S110–S114

    CAS  PubMed  Google Scholar 

  8. Massaro D, Massaro GD (2004) Estrogen regulates pulmonary alveolar formation, loss, and regeneration in mice. Am J Physiol Lung Cell Mol Physiol 287:L1154–L1159

    Article  CAS  PubMed  Google Scholar 

  9. Trotter A, Ebsen M, Kiossis E, Meggle S, Kueppers E, Beyer C, Pohlandt F, Maier L, Thome UH (2006) Prenatal estrogen and progesterone deprivation impairs alveolar formation and fluid clearance in newborn piglets. Pediatr Res 60:60–64

    Article  CAS  PubMed  Google Scholar 

  10. Massaro D, Massaro GD (2006) Estrogen receptor regulation of pulmonary alveolar dimensions: alveolar sexual dimorphism in mice. Am J Physiol Lung Cell Mol Physiol 290:L866–L870

    Article  CAS  PubMed  Google Scholar 

  11. O’Shaughnessy PJ, Baker PJ, Heikkila M, Vainio S, McMahon AP (2000) Localization of 17beta-hydroxysteroid dehydrogenase/17-ketosteroid reductase isoform expression in the developing mouse testis—androstenedione is the major androgen secreted by fetal/neonatal leydig cells. Endocrinology 141:2631–2637

    Article  PubMed  Google Scholar 

  12. Barkley MS, Geschwind II, Bradford GE (1979) The gestational pattern of estradiol, testosterone and progesterone secretion in selected strains of mice. Biol Reprod 20:733–738

    Article  CAS  PubMed  Google Scholar 

  13. Wong L, Spearow JL, Castracane VD, Barkley M (1995) Genetic variation in plasma androgens and ovarian aromatase activity during mouse pregnancy. Proc Soc Exp Biol Med 208:277–282

    CAS  PubMed  Google Scholar 

  14. Stahl F, Gotz F, Dorner G (1991) The influence of fetal adrenals on the androgen levels during brain differentiation in human subjects and rats. Exp Clin Endocrinol 98:131–139

    Article  CAS  PubMed  Google Scholar 

  15. Heikkila M, Peltoketo H, Leppaluoto J, Ilves M, Vuolteenaho O, Vainio S (2002) Wnt-4 deficiency alters mouse adrenal cortex function, reducing aldosterone production. Endocrinology 143:4358–4365

    Article  CAS  PubMed  Google Scholar 

  16. Zoetis T, Hurtt ME (2003) Species comparison of lung development. Birth Defects Res B Dev Reprod Toxicol 68:121–124

    Article  CAS  PubMed  Google Scholar 

  17. Motelica-Heino I, Castanier M, Corbier P, Edwards DA, Roffi J (1988) Testosterone levels in plasma and testes of neonatal mice. J Steroid Biochem 31:283–286

    Article  CAS  PubMed  Google Scholar 

  18. Boucher E, Provost PR, Plante J, Tremblay Y (2009) Androgen receptor and 17beta-HSD type 2 regulation in neonatal mouse lung development. Mol Cell Endocrinol 311:109–119

    Article  CAS  PubMed  Google Scholar 

  19. Drolet R, Simard M, Plante J, Laberge P, Tremblay Y (2007) Human type 2 17 beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy. Reprod Biol Endocrinol 5:30

    Article  PubMed  Google Scholar 

  20. Labrie F, Belanger A, Belanger P, Berube R, Martel C, Cusan L, Gomez J, Candas B, Castiel I, Chaussade V, Deloche C, Leclaire J (2006) Androgen glucuronides, instead of testosterone, as the new markers of androgenic activity in women. J Steroid Biochem Mol Biol 99:182–188

    Article  CAS  PubMed  Google Scholar 

  21. Hanley K, Rassner U, Jiang Y, Vansomphone D, Crumrine D, Komuves L, Elias PM, Feingold KR, Williams ML (1996) Hormonal basis for the gender difference in epidermal barrier formation in the fetal rat. Acceleration by estrogen and delay by testosterone. J Clin Invest 97:2576–2584

    Article  CAS  PubMed  Google Scholar 

  22. Kao JS, Garg A, Mao-Qiang M, Crumrine D, Ghadially R, Feingold KR, Elias PM (2001) Testosterone perturbs epidermal permeability barrier homeostasis. J Invest Dermatol 116:443–451

    Article  CAS  PubMed  Google Scholar 

  23. Ellsworth K, Harris G (1995) Expression of the type 1 and 2 steroid 5 alpha-reductases in human fetal tissues. Biochem Biophys Res Commun 215:774–780

    Article  CAS  PubMed  Google Scholar 

  24. O’Shaughnessy PJ, Baker PJ, Johnston H (2006) The foetal Leydig cell—differentiation, function and regulation. Int J Androl 29:90–95; discussion 105-108

    Google Scholar 

  25. Habert R, Picon R (1984) Testosterone, dihydrotestosterone and estradiol-17 beta levels in maternal and fetal plasma and in fetal testes in the rat. J Steroid Biochem 21:193–198

    Article  CAS  PubMed  Google Scholar 

  26. Plante J, Simard M, Rantakari P, Cote M, Provost PR, Poutanen M, Tremblay Y (2009) Epithelial cells are the major site of hydroxysteroid (17beta) dehydrogenase 2 and androgen receptor expression in fetal mouse lungs during the period overlapping the surge of surfactant. J Steroid Biochem Mol Biol 117:139–145

    Article  CAS  PubMed  Google Scholar 

  27. Provost PR, Simard M, Tremblay Y (2004) A link between lung androgen metabolism and the emergence of mature epithelial type II cells. Am J Respir Crit Care Med 170:296–305

    Article  PubMed  Google Scholar 

  28. Tremblay Y, Provost PR (2006) 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. Mol Cell Endocrinol 248:118–125

    Article  CAS  PubMed  Google Scholar 

  29. Provost PR, Boucher E, Tremblay Y (2009) Apolipoprotein A-I, A-II, C-II, and H expression in the developing lung and sex difference in surfactant lipids. J Endocrinol 200:321–330

    Article  CAS  PubMed  Google Scholar 

  30. Plante J, Simard M, Rantakari P, Cote M, Provost PR, Poutanen M, Tremblay Y (2009) Epithelial cells are the major site of hydroxysteroid (17beta) dehydrogenase 2 and androgen receptor expression in fetal mouse lungs during the period overlapping the surge of surfactant. J Steroid Biochem Mol Biol 117:139–145

    Article  CAS  PubMed  Google Scholar 

  31. Provost PR, Tremblay Y (2007) Mouse 3alpha-hydroxysteroid dehydrogenase mRNA: a marker of lung maturity. J Steroid Biochem Mol Biol 103:61–64

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grant No. 171140-05 from the Natural Sciences and Engineering Research Council of Canada (NSERC) to YT. EB received Ph.D. scholarships from the Respiratory Health Network of the Fond de Recherche en Santé du Québec (RHN-FRSQ), the Fond Québécois de la Recherche sur la Nature et les Technologies (FQRNT), and the Strategic Training Initiative in Research in Reproductive Health Sciences (STIRRHS).

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Authors and Affiliations

  1. Reproduction Axis, Perinatal and Child Health, CHUQ Research Center, 2705 Laurier Boulevard, Rm T-1-49, Quebec City, QC, Canada

    Eric Boucher, Pierre R. Provost, Audrey Devillers & Yves Tremblay

  2. Centre de Recherche en Biologie de la Reproduction (CRBR), Laval University, Quebec City, QC, Canada

    Eric Boucher, Pierre R. Provost, Audrey Devillers & Yves Tremblay

  3. Department of Obstetrics and Gynecology, Faculty of Medicine, Laval University, Quebec City, QC, Canada

    Pierre R. Provost & Yves Tremblay

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  1. Eric Boucher
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  2. Pierre R. Provost
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  3. Audrey Devillers
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  4. Yves Tremblay
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Correspondence to Yves Tremblay.

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Boucher, E., Provost, P.R., Devillers, A. et al. Levels of Dihydrotestosterone, Testosterone, Androstenedione, and Estradiol in Canalicular, Saccular, and Alveolar Mouse Lungs. Lung 188, 229–233 (2010). https://doi.org/10.1007/s00408-010-9231-x

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  • DOI: https://doi.org/10.1007/s00408-010-9231-x

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