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Antagonistic Effects of Progesterone on Estradiol-Induced Synthesis and Degradation of Uterine Glucose-6-Phosphate Dehydrogenase*

1983; Oxford University Press; Volume: 112; Issue: 2 Linguagem: Inglês

10.1210/endo-112-2-459

1945-7170

L. V. Swanson, Kenneth L. Barker,

Nitric Oxide and Endothelin Effects

Estradiol administered daily to ovariectomized mature rats stimulates uterine glucose-6-phosphate dehydrogenase (G6PD) to maximum levels within 72 h, a stimulation that is nearly 14-fold greater than the preinduced levels. Twice daily injections of progesterone given with daily estradiol injections caused the increases in G6PD activity to plateau prematurely after 36 h at levels that were 38% of the maximum estrogeninduced value at 72 h. The mechanisms of this delayed antagonistic effect of progesterone were determined by comparing the rates of uterine G6PD synthesis and degradation at various times during the 72-h response to estradiol in the presence and absence of progesterone. Progesterone first caused a significant reduction in the estradiol-induced rate of synthesis of uterine G6PD after a lag of 24 h, and the inhibition continued until 72 h, at which time rates of synthesis in animals treated with both hormones were only slightly above the rates in untreated controls. At 36 h, estradiol induced a 49% reduction in the amount of time required for ribosomes to translate the mRNA for G6PD; this rate was reduced by 38% in animals given both hormones. Both estradiol and progesterone, given separately or together, blocked degradation of uterine G6PD during the 48- to 72-h period after the initial injection of estradiol. Maximal inhibitory effects of progesterone required that progesterone be given by 12 h after the initial treatment with estradiol. The levels of uterine estradiol receptors in cytosol and nuclear compartments were measured under exchange conditions, and after 24 h, the amounts of receptors in both compartments were significantly reduced in progesterone-treated rats relative to levels seen in animals given only estradiol. Progesterone did not inhibit the estrogen-induced translocation of estradiol receptor to the nucleus, but the amount available for translocation was significantly reduced. These results suggest that the normal changes in gonadal steroid secretion during the estrous cycle permit levels of certain enzymes, such as G6PD, to be stimulated to high levels by estradiol, followed by static maintenance of the elevated levels of the enzyme due to progesterone-induced inhibition of both synthesis and degradation of the enzyme. This would allow the enzyme to function in the tissue during the progestational phase while the protein synthetic capacities of the tissue are used to synthesize progesterone-induced proteins. Continued activation of the rate of peptide elongation by estradiol during the progestational phase should decrease the time required to synthesize progesterone-induced proteins.