Biology of Reproduction, Vol 51, 800-806, Copyright © 1994 by Society for the Study of Reproduction

ARTICLES

Protein kinase C second messenger system mediates the antisteroidogenic effects of prostaglandin F2 alpha in the ovine corpus luteum in vivo

WJ McGuire, JL Juengel and GD Niswender
Department of Physiology, Colorado State University, Fort Collins 80523.

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)