Protein kinase C second messenger system mediates the antisteroidogenic effects of prostaglandin F2 alpha in the ovine corpus luteum in vivo.
Experiment I was designed to determine the optimal dose of phorbol 12-myristate 13-acetate (PMA) that inhibited progesterone production when infused into the ovarian artery. The most efficacious dose of PMA was 2 mumol. Experiment II was designed to determine whether activation of protein kinase C (PKC) inhibited progesterone production without initiating luteolysis. Ewes received ovarian arterial infusions of 4 alpha-phorbol (2 mumol, n = 4), PMA (2 mumol, n = 8), or prostaglandin F2 alpha (PGF2 alpha; 1 mumol, n = 5). Concentrations of progesterone in serum decreased by 3 h in PMA-treated ewes and by 5 h in PGF2 alpha treated ewes (p < 0.05). By 48 h, serum levels of progesterone in PMA-treated ewes had returned to control values; but in PGF2 alpha-treated ewes they remained low for the duration of the experiment. Luteal weights and progesterone contents at 48 h were similar in 4 alpha-phorbol- and PMA-treated ewes but were decreased in PGF2 alpha-treated ewes (p < 0.05). Experiment III was designed to determine whether PGF2 alpha or PKC activation induced oligonucleosome formation or influenced mRNA levels for cytochrome P450sec or 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD). Ewes received treatments as in experiment II, and CL were collected at 3, 12, or 24 h (n = 3-4 per group). Luteal weights were decreased (p < 0.05) and oligonucleosome formation was increased (p < 0.05) in PGF2 alpha-treated ewes compared to controls or to PMA-treated ewes by 12 h.(ABSTRACT TRUNCATED AT 250 WORDS)
McGuire
W J
WJ
Department of Physiology, Colorado State University, Fort Collins 80523.
Juengel
J L
JL
Niswender
G D
GD
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D010704:Phorbols / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015290:Second Messenger Systems; D012756:Sheep / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology
D010704:Phorbols; D012333:RNA, Messenger; D011374:Progesterone; D015237:Dinoprost; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C033085:phorbol