Inhibitory characteristics of prostaglandin F 2α in the rat luteal cell

Abstract

Enzymatically dispersed and enriched preparations of rat luteal cells were used to characterize the antigonadotropic effects of prostaglandin (PG) F 2α. The half-maximal dose (ED 50) of LH for stimulation of cAMP accumulation and progesterone secretion was 100 and 25 ng/ml, respectively. Methylisobutylxanthine (MIX) had no effect on the ED 50 of LH on cAMP accumulation but reduced the ED 50 of LH on progesterone secretion from 25 to 10 ng/ml. PGF 2α inhibited the tropic responses to LH by 55%–70% within minutes at concentrations of PGF 2α within the physiological range. For example, 2–4 nM PGF 2α inhibited LH-stimulated cAMP accumulation by 50% (IC 50). PGF 2α reduced the maximum cAMP response to LH but had no effect on the ED 50 of LH for cAMP accumulation whereas PGF 2α increased the ED 50 of LH on progesterone secretion by 5–7-fold. Inhibition by PGF 2α appeared to be unrelated to an effect on cAMP phosphodiesterase activity or to changes in parameters of LH receptor binding activity. No inhibition by PGF 2α was evident on LH-stimulated cAMP accumulation in isolated membranes. PGF 2α had little effect on cAMP accumulation in response to cholera toxin or forskolin but produced significant inhibition of progesterone secretion in response to cholera toxin or dibutyryl cAMP ((Bu) 2cAMP). It is concluded that the antigonadotropic effect of PGF 2α in the luteal cell is due to two interrelated actions: inhibition of activation of cAMP accumulation by LH and inhibition of the luteal cell response to cAMP. Since PGF 2α had no effect in the broken cells, it is suggested that the action of PGF 2α may be mediated by a second messenger in the intact cell.