Testicular synthesis and vitamin D action

J Clin Endocrinol Metab. 2014 Oct;99(10):3766-73. doi: 10.1210/jc.2014-1690. Epub 2014 Jun 17.

Abstract

Context: The vitamin D system has pleiotropic effects not only in bone metabolism. Its role in testicular steroidogenesis is new and deserves intensive research.

Objective: We hypothesize that vitamin D, especially 1,25 dihydroxyvitamin D3 [1,25(OH)2D3 (calcitriol)] induces male steroidogenesis and intend to identify its impact on genes and pathways in testicular androgen regulation.

Methods: Human adult primary testicular cells were isolated, treated with 1,25(OH)2D3, and their gene expression levels profiled by microarray analysis. Highly regulated genes were confirmed by real-time quantitative PCR. In addition, the effects of 1,25(OH)2D3 in combination with LH and IGF-I on the gene expression level of androgens were assessed. T levels in the culture media were determined by a high-resolution ELISA. The expression of vitamin D receptor was confirmed at baseline and after 1,25(OH)2D3 stimulation using immunocytochemistry.

Results: Microarrays depicted 63 genes significantly regulated by 1,25(OH)2D3, including genes related to male androgen and vitamin D metabolism, mainly triggered by the vitamin D receptor/retinoid X receptor activation. 1,25(OH)2D3 led to significant changes in the expression profiles of reproductive genes and significantly increased T synthesis in human testicular cell cultures.

Conclusions: Data from our human primary testicular cell culture model suggest that vitamin D plays a major role in male steroidogenesis in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Androgens / genetics
  • Androgens / metabolism*
  • Calcitriol / pharmacology*
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Luteinizing Hormone / pharmacology
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Primary Cell Culture
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Testis / cytology*
  • Testis / physiology
  • Testosterone / biosynthesis*
  • Testosterone / genetics
  • Transcriptome / drug effects*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology
  • Vitamins / pharmacology

Substances

  • Androgens
  • Receptors, Calcitriol
  • Vitamins
  • Testosterone
  • Insulin-Like Growth Factor I
  • Luteinizing Hormone
  • Calcitriol