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Journal of Andrology, Vol 10, Issue 6 449-455, Copyright © 1989 by The American Society of Andrology


JOURNAL ARTICLE

Mechanism of LHRH-stimulated steroidogenesis in rat Leydig cells: lipoxygenase products of arachidonic acid may not be involved

A. K. Didolkar and K. Sundaram
Population Council, New York, New York 10021.

Luteinizing hormone releasing hormone agonist, [(imBzl)-DHis6,Pro9,NEt]-LHRH (LHRH-A), caused a two to threefold increase in in vitro testosterone (T) secretion by rat Leydig cells. This LHRH-A-induced T secretion was completely blocked by quinacrine and chloroquine, inhibitors of phospholipase A2. Addition of phospholipase A2, however, was ineffective in stimulating basal or LHRH-A-induced T secretion. Phospholipase C, on the other hand, significantly stimulated both basal and LHRH-A-induced T secretion. Exogenously added arachidonic acid stimulated basal T secretion in a dose dependent manner, the maximum increase being about 100% over basal at a dose of 100 microM. Higher doses of arachidonic acid had no stimulatory effect. In the presence of LHRH-A, the stimulatory effect of arachidonic acid was additive up to a concentration of 100 microM; but higher concentrations of arachidonic acid (200 microM) were inhibitory. LHRH-A-induced steroidogenesis was inhibited by 5, 8, 11, 14 Eicosatetraynoic acid (ETYA), an inhibitor of all the three known pathways of arachidonic acid metabolism, and by nordihydroguaiaretic acid, and inhibitory of the lipoxygenase pathway of arachidonic acid metabolism. LHRH-A-stimulated T secretion was not inhibited by indomethacin, an inhibitor of the cyclo-oxygenase pathway of arachidonic acid metabolism. ETYA inhibited arachidonic acid-induced T secretion. Nordihydroguaiaretic acid, on the other hand, augmented basal, arachidonic acid-, phospholipase C-, or phorbol 12, myristate 13 acetate-induced testosterone secretion. These results suggest that arachidonic acid, whose release is influenced by phospholipase C, is involved in LHRH-A-induced T secretion by rat Leydig cells.(ABSTRACT TRUNCATED AT 250 WORDS)





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Copyright © 1989 by The American Society of Andrology.