Sphingomyelinase affects hormone production by JEG-3 choriocarcinoma cells

Donald R. McClelland, Brooke Bourdelat-Parksi, Kaiman Salata, Gary L. Francis

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Critical illness affects the function of several endocrine organs, perhaps through the effects of cytokines including tumor necrosis factor-α (TNF-α). Although the mechanism by which TNF-α affects cell function is not fully known, the activation of sphingomyelinase by TNF-α and the subsequent liberation of ceramide have been recently proposed as important parts of the cellular effects of TNF-α. In previous studies, the cellular events which follow the activation of endogenous sphingomyelinase by TNF-α have been replicated in vitro by the direct addition of exogenous sphingomyelinase alone. In these studies, sphingomyelinase has been shown to inhibit the synthesis of cholesterol in fibroblasts and testosterone in Leydig cells, and to decrease P450-aromatase activity in granulosa cells. Using a JEG-3 choriocarcinoma cell model, the present study was designed to determine if sphingomyelinase might also affect placental hormone synthesis. The data show that sphingomyelinase significantly increased the basal production of progesterone, estradiol, and human chorionic gonadotropin (hCG) and further increased dibutyryl-adenosine 3':5'-cyclic monophosphate (dBcAMP) stimulated progesterone and hCG. These data show that exogenous sphingomyelinase affects JEG-3 hormone production and suggest that sphingomyelinase and dBcAMP may have additive effects on progesterone and hCG synthesis. The present study also investigated the effects of ceramide on JEG-3 function. In contrast to sphingomyelinase, ceramide alone increased the synthesis of progesterone but had no effect on either estradiol or hCG. These latter findings suggest that ceramide generation may be only one part of the cellular events which occur following sphingomyelinase exposure.

Original languageEnglish (US)
Pages (from-to)19-24
Number of pages6
JournalEndocrinology and Metabolism, Supplement
Volume4
Issue number1
StatePublished - Jan 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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