title: Human testicular peritubular cells host putative stem Leydig cells with steroidogenic capacity.
abstract: OBJECTIVE
  We aim to examine the steroidogenic phenotype and the differentiation potential of human testicular peritubular cells (HTPCs) and to explore their possible relationship to the adult Leydig cell lineage.
  
  
  BACKGROUND
  The cells of the adult Leydig cell lineage may reside in the peritubular compartment of the testis. This suggestion is supported by the facts that the rodent peritubular cells can be differentiated toward this lineage and that cAMP enhances their steroidogenic potential.
  
  
  METHODS
  Human testicular biopsies, and derived HTPCs, were analyzed by immunohistochemistry, RT-PCR, and Western blotting. After stimulation by forskolin or platelet-derived growth factor-BB, quantitative RT-PCR was used to compare the levels of mRNAs encoding proteins involved in steroidogenesis and steroid production was analyzed by liquid chromatography and tandem mass spectrometry.
  
  
  RESULTS
  Immunohistochemical analysis revealed that the peritubular cells that form the outer part of the tubular wall express platelet derived growth factor receptor-α. Furthermore, the pluripotency markers (POU domain class 5 transcription factor 1, GATA-binding protein 4), stem Leydig cell markers (platelet derived growth factor receptor-A, leukemia inhibitory factor receptor), and mRNAs encoding proteins involved in steroidogenesis (nuclear receptor subfamily 5, group A, member 1; steroidogenic acute regulatory protein; CYP11A1; CYP17A1; 3β-hydroxysteroid dehydrogenase) were expressed by the HTPCs. Stimulation with forskolin increased the expression of the steroidogenic markers, which was accompanied by the production of pregnenolone and progesterone by HTPCs in vitro. Treatment with platelet-derived growth factor-BB induced expression of steroidogenic acute regulatory protein.
  
  
  CONCLUSIONS
  Our results indicate that the tubular wall of the human testis is a reservoir for cells of the adult Leydig cell lineage and that the steroidogenic potential of these cells can be activated in culture.
authors.affiliation: Department of Women's and Children's Health (L.L., O.S., K.Sv.), Karolinska Institutet, 171 76 Stockholm, Sweden; Department of Anatomy III-Cell Biology (K.Sp., K.Sc., A.M.), Ludwig Maximilian University, 80336 Munich, Germany; School of Pharmacy (M.R.H., S.A.), University of Eastern Finland, 70211 Kuopio, Finland; and Turku Center for Disease Modeling (M.P.), Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
authors.forename: Luise
authors.initials: L
authors.lastname: Landreh
authors.forename: Katrin
authors.initials: K
authors.lastname: Spinnler
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schubert
authors.forename: Merja R
authors.initials: MR
authors.lastname: Häkkinen
authors.forename: Seppo
authors.initials: S
authors.lastname: Auriola
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
authors.forename: Olle
authors.initials: O
authors.lastname: Söder
authors.forename: Konstantin
authors.initials: K
authors.lastname: Svechnikov
authors.forename: Artur
authors.initials: A
authors.lastname: Mayerhofer
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D015870:Gene Expression; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D000071317:Nanog Homeobox Protein; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013737:Testis / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D012739:Gonadal Steroid Hormones; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D020796:Receptor, Platelet-Derived Growth Factor alpha