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Differential effects of tumor necrosis factor-α and interleukin-1 on 3β-hydroxysteroid dehydrogenase/Δ5→Δ4 isomeraseexpression in mouse Leydig cells

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Abstract

Immune-endocrine interactions are important to the regulation of Leydig cell steroidogenesis. We have shown previously that both tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1-β) inhibit 8-bromo-cAMP-(8-Br-cAMP)-stimulated steroidogenesis in mouse Leydig cells. TNF and IL-1 both inhibit cAMP-stimulated testosterone production as well as mRNA and protein levels of cholesterol side chain cleavage enzyme (P450scc) and 17α-hydroxylase/C17,20 lyase (P450c17) in mouse Leydig cells. Neither TNF nor IL-1 affects basal levels of P450scc mRNA and protein. In the present study, we tested the effects of TNF and IL-1 on basal testosterone production and 8-Br-cAMP-stimulated 3β-hydroxysteroid dehydrogenase/Δ5→Δ4 isomerase(3βHSD) expression in Leydig cells. Purified and macrophage-depleted Leydig cells were cultured for 5 d with daily changes of media, and then treated with increasing concentrations of recombinant mouse TNF or IL-1 in the presence or absence of 8-Br-cAMP (50 μM) for 24 h. The media were collected for testosterone RIA and RNA and protein were extracted from cells. Basal testosterone production was inhibited by TNF, but not IL-1. Treatment of Leydig cells with 8-Br-cAMP alone caused a marked increase in 3βHSD mRNA, and protein levels. Both TNF and IL-1 inhibited cAMP-stimulated 3βHSD mRNA and protein levels, but only TNF inhibited basal 3βHSD expression. These results demonstrate that TNF and IL-1 have different effects on basal steroidogenesis in Leydig cells and suggest that TNF-mediated inhibition of basal testosterone production may be owing to the inhibition of basal 3β-HSD expression in Leydig cells.

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Authors and Affiliations

  1. Department of Physiology and Biophysics (M/C 901), University of Illinois at Chicago, 835 S Wolcott Ave., 60612-7342, Chicago, IL

    Yuting **ong & Dale Buchanan Hales PhD

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  1. Yuting **ong
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  2. Dale Buchanan Hales PhD
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Correspondence to Dale Buchanan Hales PhD.

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**ong, Y., Hales, D.B. Differential effects of tumor necrosis factor-α and interleukin-1 on 3β-hydroxysteroid dehydrogenase/Δ5→Δ4 isomeraseexpression in mouse Leydig cells. Endocr 7, 295–301 (1997). https://doi.org/10.1007/BF02801322

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  • DOI: https://doi.org/10.1007/BF02801322

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