Involvement of the phospholipase C second messenger system in the regulation of steroidogenesis in small bovine luteal cells.
We have previously suggested that the interaction between luteinizing hormone (LH) and its receptor, in addition to stimulating adenylate cyclase, is able to trigger a negative regulatory signal at a step beyond cAMP synthesis (Benhaim et al. (1987) FEBS Lett. 223, 321-326). The present study was conducted to determine whether the phospholipase C system is involved in this phenomenon. Small bovine luteal cells from pregnant cows were incubated with phospholipase C, A23187, an ionophore of calcium and/or phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), in the presence or absence of bovine luteinizing hormone or dibutyryl cyclic AMP (dbcAMP). A23187 associated with PMA was able to mimic the stimulatory effect of phospholipase C on basal progesterone production, whereas neither A23187 nor PMA alone had any effect. In the presence of high doses of LH, phospholipase C inhibited progesterone and cAMP production in a dose-dependent manner. A23187 and PMA were able to mimic the inhibition of progesterone synthesis but stimulated LH-induced cAMP accumulation. When cells were stimulated by high doses of dbcAMP, phospholipase C and A23187 but not PMA inhibited progesterone synthesis. These observations suggest that (1) phospholipase C can mimic the post-cAMP negative regulatory signal induced in vitro by high doses of LH, in the presence of an activation of PKC; (2) phospholipase C is also able to mimic in vitro the luteolytic properties of prostaglandin F2 alpha that we previously described (Benhaim et al. (1987) Prostaglandins 33, 227-239); and (3) under basal conditions or in the presence of low doses of LH, the phospholipase C system slightly stimulates steroidogenesis.
Benhaim
A
A
Laboratoire de Biochimie, CNRS UA-609, CHU Côte de Nacre, Caen, France.
Bonnamy
P J
PJ
Mittre
H
H
Leymarie
P
P
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D003338:Corpus Luteum / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D066298:In Vitro Techniques; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*; D013256:Steroids / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism* / Q000494:pharmacology
D013256:Steroids; D000001:Calcimycin; D011374:Progesterone; D003994:Bucladesine; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate