ESTRADIOL AND CHLORDECONE (KEPONE) DECREASE ADENOSINE 3'5'-CYCLIC MONOPHOSPHATE CONCENTRATIONS IN THE OVARIECTOMIZED IMMATURE RAT UTERUS

Adenosine 3'5'-cyclic monophosphate (cAMP) has been repeatedly shown t o mimic some actions of estrogen in the rat uterus. However, the relat ionship between estrogens and uterine cAMP remains controversial. The effect of chronic exposure (3 days) to a biologically potent, long-act ing estrogen, estradiol benzoate (EB), or the xenoestrogen chlordecone (Kepone), which has a long half-life in the circulation, was examined in ovariectomized immature rats. Both compounds, when administered in doses that provided equal increases in uterine weight, produced equiv alent decreases in uterine cAMP content. Although the decrease in cAMP was apparent within 48 hr, it was more pronounced at 72 hr. There was no reduction in cAMP produced in response to direct stimulation of ut erine adenylyl cyclase by forskolin, Indicating that loss of the enzym e was not a factor in the lowering of cAMP content. The pure anti-estr ogen ICI-182,780, in a dose-dependent fashion, prevented the action th e estradiol benzoate and chlordecone, suggesting that the lowering of cAMP was dependent on an estrogen receptor. The physiological signific ance of reduced uterine cAMP with chronic estrogen treatment remains t o be determined.