Cyclic nucleotide phosphodiesterase activity in the quail oviduct: hormonal regulation and involvement in estrogen-induced growth.
A previous study has shown that cAMP was involved in estrogen-activated growth in the quail oviduct. The present study was undertaken to investigate the hormonal regulation of 3',5'-cyclic nucleotide phosphodiesterase activity in the oviduct. Tamoxifen, an antiestrogen compound, and 3-isobutyl-1-methylxanthine, an inhibitor of phosphodiesterase, were also used to determine the relationship between estradiol-induced cell proliferation and cAMP phosphodiesterase activity. Cyclic nucleotide phosphodiesterase was almost completely restricted to the cytosolic fraction (108,000 X g supernatant) of the quail oviduct homogenate. By affinity chromatography on immobilized calmodulin, we separated and partially characterized three different forms of the enzyme. They differed in their cyclic nucleotide specificities, kinetics, and sensitivity to calmodulin. In vivo, estradiol benzoate (EB) modulated crude cytosolic phosphodiesterase activity. cAMP and cyclic-GMP hydrolyzing activities increased between 12 and 48 h after a single injection of EB and then declined to return to control value by 96 h. Estrone, 17 alpha-estradiol, progesterone, and testosterone were ineffective, while estriol slightly increased cyclic-GMP hydrolyzing activity. When administered with EB, tamoxifen drastically increased oviduct cAMP concentration while it completely inhibited oviduct growth and the activation of cAMP phosphodiesterase induced by EB alone. Moreover, 3-isobutyl-1-methylxanthine produced a dose-dependent inhibition of oviduct cell proliferation when given with EB. These results demonstrate that the activation of cAMP phosphodiesterase after an injection of EB and the subsequent decrease in oviduct cAMP concentration are necessary for the epithelial cells to achieve their proliferative cycle.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D000375:Aging; D000818:Animals; D003370:Coturnix; D004958:Estradiol / Q000494:pharmacology; D004964:Estriol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D010057:Oviducts / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*; D013629:Tamoxifen / Q000494:pharmacology*
D004967:Estrogens; D013629:Tamoxifen; D004970:Estrone; D004958:Estradiol; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D004964:Estriol; D015056:1-Methyl-3-isobutylxanthine