Inhibitory characteristics of prostaglandin F2 alpha in the rat luteal cell.
Enzymatically dispersed and enriched preparations of rat luteal cells were used to characterize the antigonadotropic effects of prostaglandin (PG) F2 alpha. 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. PGF2 alpha inhibited the tropic responses to LH by 55-70% within minutes at concentrations of PGF2 alpha within the physiological range. For example, 2-4 nM PGF2 alpha inhibited LH-stimulated cAMP accumulation by 50% (IC50). PGF2 alpha reduced the maximum cAMP response to LH but had no effect on the ED50 of LH for cAMP accumulation whereas PGF2 alpha increased the ED50 of LH on progesterone secretion by 5-7-fold. Inhibition by PGF2 alpha appeared to be unrelated to an effect on cAMP phosphodiesterase activity or to changes in parameters of LH receptor binding activity. No inhibition by PGF2 alpha was evident on LH-stimulated cAMP accumulation in isolated membranes. PGF2 alpha 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 PGF2 alpha 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 PGF2 alpha had no effect in the broken cells, it is suggested that the action of PGF2 alpha may be mediated by a second messenger in the intact cell.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D015237:Dinoprost; D004305:Dose-Response Relationship, Drug; D005260:Female; D007986:Luteinizing Hormone / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis; D011460:Prostaglandins F / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D011460:Prostaglandins F; D011374:Progesterone; D003994:Bucladesine; D007986:Luteinizing Hormone; D002772:Cholera Toxin; D015237:Dinoprost; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015056:1-Methyl-3-isobutylxanthine