Effect of various steroids on the biosynthesis of arachidonic acid in isolated hepatocytes and HTC cells.
The effect of various steroids on the incorporation and desaturation of eicosa-8,11,14-trienoic acid in normal hepatocytes and HTC cells was investigated. After 3 hr incubation with 11-deoxycorticosterone, both kinds of cells showed an increase in the incorporation of eicosatrienoic acid. In contrast, progesterone, cortexolone, 17-beta-estradiol, testosterone, estriol, aldosterone, corticosterone, dexamethasone, dehydroepiandrosterone, 11-beta-hydroxyandrosterone, 11-ketoaetiocholanolone, epiaetiocholanolone and 5-beta-pregnane-3 alpha,20 alpha-diol, provoked no significant changes in the uptake of the exogenous acid. Of all the steroids tested, only 11-deoxycorticosterone, dexamethasone and 17-beta-estradiol evoked a significant inhibition on the arachidonate biosynthesis in both kinds of cells. Testosterone, estriol, aldosterone and corticosterone provoked a significant inhibition of delta 5-desaturase in HTC cells. In dexamethasone, this effect was dose-dependent (0 to 10(-4) M). Simultaneous incubation with 17-beta-estradiol or 11-deoxycorticosterone with dexamethasone led to an extent of inhibition on arachidonate biosynthesis that did not surpass the effect of each drug. Pretreatment of isolated hepatocytes with the antiglucocorticoid, cortexolone, prevented the dexamethasone-induced inhibition of arachidonate biosynthesis. Normal rat liver microsomes preincubated in vitro with dexamethasone, 11-deoxycorticosterone, 17-beta-estradiol, corticosterone or estriol (10(-6) or 10(-4) M concentration), showed no significant changes in the delta 5-desaturase activity. The results obtained suggest that the effect of the steroids on arachidonic acid biosynthesis in normal hepatocytes and HTC cells requires receptor occupancy and probably is mediated through a common biochemical mechanism.
Marra
C A
CA
Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET-UNLP, Facultad de Ciencias Médicas, La Plata, Argentina.
de Alaniz
M J
MJ
Brenner
R R
RR
D015126:8,11,14-Eicosatrienoic Acid / Q000378:metabolism; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000096:biosynthesis*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008901:Mineralocorticoids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013256:Steroids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000728:Androgens; D001095:Arachidonic Acids; D004967:Estrogens; D005938:Glucocorticoids; D008901:Mineralocorticoids; D013256:Steroids; D016718:Arachidonic Acid; D015126:8,11,14-Eicosatrienoic Acid