Tumor necrosis factor-alpha inhibits leydig cell steroidogenesis through a decrease in steroidogenic acute regulatory protein expression

Endocrinology. 1998 Jun;139(6):2863-8. doi: 10.1210/endo.139.6.6077.


The aim of the present study was to identify the sites of the inhibitory action of TNFalpha (tumor necrosis factor alpha) on LH/hCG-stimulated testosterone formation. By using cultured porcine Leydig cells as a model, TNFalpha was shown to inhibit testosterone secretion when testicular cells were stimulated with hCG but not when incubated with 22R-hydroxycholesterol (a cholesterol substrate derivative that readily passes through cell and mitochondrial membranes). Such an observation suggested that the cytokine may affect cholesterol transport and/or availability to cytochrome P450scc in the mitochondria. Specifically, we report here that TNFalpha reduced in a dose- and time-dependent manner hCG-induced StAR (steroidogenic acute regulatory protein) levels. The maximal and half-maximal effects were obtained with 20 ng/ml (1.2 nM) and 1.6 ng/ml (0.09 nM) of TNFalpha, respectively. Maximal inhibitory effects of TNFalpha on StAR messenger RNA and protein levels were obtained after 48 h of treatment. Additionally, the presence of TNFalpha receptors P55 in terms of protein (identified through cross-linking experiments) and messenger RNA (identified through RT-PCR analysis) suggested that the effects of the cytokine are directly exerted on the testicular steroidogenic cell type.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Cells, Cultured
  • Cholesterol / metabolism
  • Chorionic Gonadotropin / pharmacology
  • Humans
  • Leydig Cells / metabolism*
  • Luteinizing Hormone / pharmacology
  • Male
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Swine
  • Testosterone / antagonists & inhibitors*
  • Testosterone / biosynthesis
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Chorionic Gonadotropin
  • Phosphoproteins
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • steroidogenic acute regulatory protein
  • Testosterone
  • Luteinizing Hormone
  • Cholesterol