title: Bone mineral density and testicular failure: evidence for a role of vitamin D 25-hydroxylase in human testis.
abstract: OBJECTIVE
  Mutations in the CYP2R1 gene, highly expressed in the testis and encoding vitamin D 25-hydroxylase, result in a vitamin D deficiency and a defective calcium homeostasis leading to rickets.
  
  
  OBJECTIVE
  Our aim was to investigate CYP2R1 expression in pathological testis samples and relate this to vitamin D metabolism in testiculopathic patients. DESIGN, PATIENTS, SETTING: Testis samples for in vitro study and 98 young men were transversally evaluated at Padova's Center for Male Gamete Cryopreservation.
  
  
  METHODS
  CYP2R1 mRNA expression and protein production were evaluated by quantitative RT-PCR, Western blot analysis, and immunofluorescence. Hormonal and bone-marker levels, and bone densitometry by dual-energy x-ray absorptiometry, were determined in patients with Sertoli-cell-only syndrome and severe hypospermatogenesis.
  
  
  RESULTS
  We found a lower gene and protein expression of CYP2R1 in samples with hypospermatogenesis and Sertoli-cell-only syndrome (P < 0.05) and a colocalization with INSL-3, a Leydig cell marker, at immunofluorescence. In all testiculopathic patients 25-hydroxyvitamin D levels were significantly lower and PTH levels higher compared to controls (P < 0.05). Furthermore, testiculopathic patients showed osteopenia and osteoporosis despite normal testosterone levels compared with controls both with increased bone-marker levels and altered dual-energy x-ray absorptiometry in the femoral neck and lumbar spine (for all parameters, P < 0.05).
  
  
  CONCLUSIONS
  Our data show an association between testiculopathy and alteration of the bone status, despite unvaried androgen and estrogen levels and no other evident cause of vitamin D reduction. Further studies in larger cohorts are needed to confirm our results.
authors.affiliation: Department of Histology, Microbiology, and Medical Biotechnologies, Section of Clinical Pathology and Centre for Male Gamete Cryopreservation, University of Padova, Via Gabelli 63, 35121 Padova, Italy. carlo.foresta@unipd.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Foresta
authors.forename: Giacomo
authors.initials: G
authors.lastname: Strapazzon
authors.forename: Luca
authors.initials: L
authors.lastname: De Toni
authors.forename: Lisa
authors.initials: L
authors.lastname: Perilli
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Mambro
authors.forename: Barbara
authors.initials: B
authors.lastname: Muciaccia
authors.forename: Leonardo
authors.initials: L
authors.lastname: Sartori
authors.forename: Riccardo
authors.initials: R
authors.lastname: Selice
mesh_terms: D000328:Adult; D053713:Azoospermia / Q000151:congenital; D015519:Bone Density / Q000235:genetics / Q000502:physiology*; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015331:Cohort Studies; D000072467:Cytochrome P450 Family 2; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007248:Infertility, Male / Q000209:etiology / Q000235:genetics / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D009845:Oligospermia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054331:Sertoli Cell-Only Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D013733:Testicular Diseases / Q000150:complications / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D013737:Testis / Q000378:metabolism / Q000473:pathology; D014807:Vitamin D / Q000378:metabolism
chemical_list: D014807:Vitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase