Prostaglandin F2 alpha-induced functional luteolysis: interactions of LH, prostaglandin F2 alpha and forskolin in cyclic AMP and progesterone synthesis in isolated rat luteal cells.
The acute antigonadotrophic action of prostaglandin F2 alpha (PGF2 alpha) was examined in dispersed luteal cell preparations from immature superluteinized rat ovaries. Cell suspensions prepared by collagenase digestion and purification over a Percoll density gradient were incubated for 1 h in Eagle's minimum essential medium in the presence and/or absence of LH, PGF2 alpha, N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP) and forskolin. Medium was assayed for total progesterone and adenosine 3',5'-cyclic monophosphate (cAMP). Luteal cell preparations showed typical steroidogenic (progesterone) responses to LH, mimicked by both dbcAMP and forskolin. Whilst the threshold LH dose to increase cAMP synthesis was greater than that for progesterone (100 micrograms/l compared with 1 microgram/l), 24 mumol forskolin/l was the threshold dose for both cAMP and progesterone responses. Furthermore, combined doses of LH and forskolin synergistically raised cAMP yet produced less than additive increases in progesterone. Similarly, combinations of dbcAMP plus forskolin produced less than additive progesterone increases. These data suggest that forskolin may not act as a simple mimic of LH. Prostaglandin F2 alpha dose-dependently inhibited forskolin-induced cAMP and progesterone synthesis and also inhibited progesterone synthesis induced by dbcAMP. These data suggest that the antigonadotrophic effect of PGF2 alpha has more than one locus of action, i.e. it both inhibits an adenylate cyclase event associated with cAMP generation and blunts the cellular response to cAMP. The present uncertainty over the exact locus of forskolin's action within the adenylate cyclase complex limits further delineation of the inhibitory action of PGF2 alpha on LH-responsive adenylate cyclase.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects*; D000242:Cyclic AMP / Q000096:biosynthesis*; D015237:Dinoprost; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000494:pharmacology*; D011374:Progesterone / Q000096:biosynthesis*; D011460:Prostaglandins F / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011460:Prostaglandins F; D005576:Colforsin; D011374:Progesterone; D003994:Bucladesine; D007986:Luteinizing Hormone; D015237:Dinoprost; D000242:Cyclic AMP