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Am J Physiol Endocrinol Metab 256: E221-E226, 1989;
0193-1849/89 $5.00
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AJP - Endocrinology and Metabolism, Vol 256, Issue 2 E221-E226, Copyright © 1989 by American Physiological Society

ARTICLES

Effect of epoxyeicosatrienoic acids on growth hormone release from somatotrophs

G. D. Snyder, P. Yadagiri and J. R. Falck
Department of Obstetrics and Gynecology, University of Iowa, Iowa City 52242.

Growth hormone secretion was stimulated in vitro by products of arachidonic acid epoxygenase, the epoxyeicosatrienoic acids. 5,6-Epoxyeicosatrienoic and 14,15-epoxyeicosatrienoic acid stimulated growth hormone release from an enriched population of somatotrophs (approximately 85%) by twofold. Inhibition of arachidonic acid metabolism by indomethacin did not affect growth hormone-releasing hormone stimulation of growth hormone release. In contrast, pretreatment of somatotrophs with an 11,12-isonitrile analogue of arachidonic acid that inhibits arachidonic acid epoxygenase, resulted in a 20-25% inhibition of growth hormone-releasing hormone-stimulated growth hormone release. 14,15-Epoxyeicosatrienoic acid stimulated a concentration-dependent increase (twofold) in the cytoplasmic concentration of adenosine 3',5'-cyclic monophosphate (cAMP) in the somatotrophs. 14,15-Epoxyeicosatrienoic acid also rapidly increased the intracellular free calcium concentration in somatotrophs from resting levels (approximately 80 nM) to greater than 250 nM. Growth hormone-releasing hormone increased the free intracellular calcium to 160-180 nM. Preincubation of somatotrophs with somatostatin inhibited growth hormone-releasing hormone-stimulated growth hormone secretion, cAMP accumulation, and 14,15-epoxyeicosatrienoic acid stimulated cAMP accumulation. These data are suggestive that the epoxyeicosatrienoic acids may have a role in the secretion of growth hormone.


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