title: Phenotype and steroidogenic potential of PDGFRα-positive rat neonatal peritubular cells.
abstract: Platelet-derived growth factor receptor α (PDGFRα)-positive peritubular cells (PTCs) are suggested to be putative stem Leydig cells. At present little is known about their phenotype and steroidogenic potential. We isolated highly purified PDGFRα-positive neonatal PTCs by magnetic cell sorting (MACS) from 8dpp rat testes and characterized them in vitro. We have demonstrated that PDGFRα-positive PTCs have a mixed phenotype. They expressed PTC-specific genes (αSma, Myh11), pluripotency markers (Pou5f1, nestin, Lifr) and genes encoding steroidogenic enzymes. Treatment with the cAMP-analog (Bu)2cAMP for 7 days upregulated steroidogenic enzyme gene expression and significantly increased their steroidogenic potential. The main end-point steroid was progesterone due to rapid inactivation of CYP17 and 17βHSD. Long-term culturing of PDGFRα-positive PTCs increased the expression of Myh11, and treatment with (Bu)2cAMP attenuated this process. All together, our findings support the hypothesis that neonatal PDGFRα-positive PTCs are steroidogenic competent progeny of stem Leydig cells (SLCs) which give rise to the adult Leydig cell lineage.
authors.affiliation: Department of Women's and Children's Health, Pediatric Endocrinology Unit, Karolinska Institutet and University Hospital, Solna, Sweden.
authors.forename: Luise
authors.initials: L
authors.lastname: Landreh
authors.forename: Jan-Bernd
authors.initials: JB
authors.lastname: Stukenborg
authors.forename: Olle
authors.initials: O
authors.lastname: Söder
authors.forename: Konstantin
authors.initials: K
authors.lastname: Svechnikov
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis; D007381:Intermediate Filament Proteins / Q000378:metabolism; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000378:metabolism; D007985:Leydig Cells / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D010641:Phenotype; D061251:Primary Cell Culture; D011374:Progesterone / Q000096:biosynthesis*; D011375:Progesterone Reductase / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D015290:Second Messenger Systems; D012671:Seminiferous Tubules / Q000166:cytology; D013234:Stem Cells / Q000502:physiology; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013251:Steroid Isomerases / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*; D059467:Transcriptome
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D012739:Gonadal Steroid Hormones; D007381:Intermediate Filament Proteins; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507842:Lifr protein, rat; D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D013739:Testosterone; D011374:Progesterone; D000242:Cyclic AMP; D011375:Progesterone Reductase; C582555:CYP17A1 protein, rat; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D020796:Receptor, Platelet-Derived Growth Factor alpha; D013251:Steroid Isomerases