Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 372, Issue 1-2, Pages 96-104Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2013.03.019
Keywords
Testis; Neonatal peritubular cells; PDGFR alpha; Stem cells
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Funding
- Karolinska Institutet
- Frimurare Barnhuset in Stockholm
- Stiftelsen Olle Engkvist Byggmastare
- Pediatric Research Foundation
- Sallskapet Barnavard
- Vetenskapsradet (VR), VR/FA
- Barncancerfonden
- Deutsche Forschungsgemeinschaft (DFG) [STU 506/3-1]
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Platelet-derived growth factor receptor alpha (PDGFR alpha)-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 PDGFR alpha-positive neonatal PTCs by magnetic cell sorting (MACS) from 8dpp rat testes and characterized them in vitro. We have demonstrated that PDGFR alpha-positive PTCs have a mixed phenotype. They expressed PTC-specific genes (alpha Sma, Myh11), pluripotency markers (Pou5f1, nestin, Lifr) and genes encoding steroidogenic enzymes. Treatment with the cAMP-analog (Bu)(2)cAMP 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 17 beta HSD. Long-term culturing of PDGFRa-positive PTCs increased the expression of Myh11, and treatment with (Bu)(2)cAMP attenuated this process. All together, our findings support the hypothesis that neonatal PDGFR alpha-positive PTCs are steroidogenic competent progeny of stem Leydig cells (SLCs) which give rise to the adult Leydig cell lineage. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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