Gonadal steroid effects on LH response to arachidonic acid and protein kinase C

Cultured rat pituitary cells were used to examine, first, the effects of luteinizing hormone-releasing hormone, Ca2+ mobilization, protein kinase C (PKC) activation, and arachidonic acid (AA) on luteinizing hormone (LH) secretion and AA release, and, second, gonadal steroid modulation of these effects. A23187, 12-O-tetradecanoylphorbol 13-acetate (TPA), and AA stimulated LH secretion by both perifused and static cultures; TPA facilitated the responses to both A23187 and AA. LHRH, A23187, and TPA stimulated AA release. Inhibition of AA metabolism reduced the LH responses to LHRH, A23187, TPA, and melittin. Pretreatment with testosterone inhibited the LH response to LHRH but not the responses to TPA or AA. Pretreatment with 17 beta-estradiol stimulated the LH responses to LHRH, TPA, and low concentrations of AA. These results suggest that LHRH action involves a cascade of events, in which the effects of Ca2+ mobilization and PKC activation are mediated at least in part by AA release. They further suggest that both testosterone and 17 beta-estradiol modulate LH secretion by affecting AA release; 17 beta-estradiol may also affect some process subsequent to AA release.