Inhibitory characteristics of prostaglandin F_2α in the rat luteal cell

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 (ED₅₀) of LH for stimulation of cAMP accumulation and progesterone secretion was 100 and 25 ng/ml, respectively. Methylisobutylxanthine (MIX) had no effect on the ED₅₀ of LH on cAMP accumulation but reduced the ED₅₀ 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% (IC₅₀). PGF_2α reduced the maximum cAMP response to LH but had no effect on the ED₅₀ of LH for cAMP accumulation whereas PGF_2α increased the ED₅₀ 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.