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  • Title: Metabolic control mechanisms in mammalian systems. XV. Studies on the role of adenosine 3' ,5'-monophosphate in estrogen action on the uterus.
    Author: Singhal RL, Lafreniere RT.
    Journal: J Pharmacol Exp Ther; 1972 Jan; 180(1):86-97. PubMed ID: 4110809.
    Abstract:
    The effects of exogenously administered 3',5'-monophosphate (cyclic AMP) on glycogen synthesis and hexose monophosphate shunt enzymes were studied in the uteri of immature and ovariectomized rats to determine whether cyclic AMP mimics the known effects of estrogenic hormones. The injection of cyclic AMP concurrently with theophylline, significantly increased the activity of uterine hexokinase, phosphofructokinase, pyruvate kinase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and uterine glycogen content in immature rats (p less than .05). These increases were related to the dose of cyclic AMP, and as little as .2 mg was able to stimulate uterine glycogen to 169% of control values. The treatment did not significantly increase the activity of the key glycolytic or hexose monophosphate shunt enzymes in the lung and thymus, although these tissues are also not receptive to estrogen. Neither estradiol-17beta or cyclic AMP and theophylline produced any measurable effect on the uterine enzymes, isocitrate dehydrogenase, or alpha-glycerophosphate dehydrogenase. In ovariectomized and adrenalectomized-ovariectomized animals, cyclic AMP and theophylline significantly stimulated the activity of key glycolytic and hexose monophosphate shunt enzymes (p less than .05); the N6, 02-dibutyryl analog of cyclic AMP being more potent than the parent compound. Pretreatment with actinomycin or cycloheximide significantly inhibited the effects of cyclic AMP and theophylline (p less than .05), which indicates that neither cyclic AMP stimulation or the inhibition of the effects of cyclic AMP were dependent on adrenal function. The results support the possiblity that cyclic AMP may be involved in mediating the metabolic effects of estrogen on the uterus.
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