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. 1995 Aug;6(8):1037–1047. doi: 10.1091/mbc.6.8.1037

Dependence of stimulus-transcription coupling on phospholipase D in agonist-stimulated pituitary cells.

M Cesnjaj 1, L Zheng 1, K J Catt 1, S S Stojilkovic 1
PMCID: PMC301261  PMID: 7579706

Abstract

Stimulation of phospholipase D activity is frequently observed during agonist activation of Ca(2+)-mobilizing receptors, but the cellular functions of this signaling pathway are not well defined. Pituitary gonadotrophs express Ca(2+)-mobilizing receptors for gonadotropin-releasing hormone (GnRH) and endothelin (ET), activation of which stimulates luteinizing hormone secretion and transient expression of c-fos. In pituitary cells and alpha T3-1 gonadotrophs, GnRH action was associated with both initial and sustained diacylglycerol (DG) production, whereas ET-1 induced only a transient DG response. Also, phospholipase D activity, estimated by the production of phosphatidylethanol from phosphatidylcholine in the presence of ethanol, was stimulated by GnRH but not ET-1. Such formation of phosphatidylethanol at the expense of phosphatidic acid (PA) during GnRH-induced activation of phospholipase D significantly reduced the production of PA, DG, and cytidine diphosphate diacylglycerol. Inhibition of PA-phosphohydrolase activity by propranolol also decreased GnRH-induced DG production and, in contrast to ethanol, increased PA and cytidine diphosphate diacylglycerol levels. The fall in DG production caused by ethanol and propranolol was accompanied by inhibition of GnRH-induced c-fos expression, whereas agonist-induced luteinizing hormone release was not affected. In contrast to their inhibitory actions on GnRH-induced early gene expression, neither ethanol nor propranolol affected ET-1-induced c-fos expression, or GnRH- and ET-1-induced inositol trisphosphate/Ca2+ signaling. These findings demonstrate that phospholipase D participates in stimulus-transcription but not stimulus-secretion coupling, and indicate that DG is the primary signal for this action.

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Selected References

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