Mechanism of the luteolytic action of prostaglandin F-2 alpha in the rat.

PGF-2 alpha suppresses the LH-induced accumulation of cyclic AMP in young and mature corpora lutea (CL) of pseudopregnant rats, with mature CL being more sensitive. Calcium ions, and later phospholipase C activation, are believed to mediate this effect. In isolated CL of 2 and 10 days of age, depletion of extracellular calcium, or addition of calmodulin inhibitors or of 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxy-benzoate (TMB-8), did not prevent the suppressive effect of PGF-2 alpha. Phorbol 12-myristate 13-acetate augmented, rather than inhibited, the LH-induced cAMP accumulation in young and mature CL. Polyphosphoinositide turnover was stimulated by PGF-2 alpha in young, but not in mature CL. The suppression by PGF-2 alpha of luteal cAMP is therefore apparently not mediated by phospholipase C activation but two phosphodiesterase inhibitors, 3-isobutyl-1-methylxanthine and Ro-20-1724, abolished the inhibitory effect of PGF-2 alpha.