Cyclic Change of Estradiol Metabolic Enzymes in Human Endometrium During the Menstrual Cycle

Abstract

Estradiol dehydrogenase (E₂DH), estrogen sulfatase and sulfotransferase are the three major estrogen metabolic enzymes found to be present in the human endometrium. The activities of these enzymes were compared in a group of normal endometrial specimens at various stages of the menstrual cycle. The average value of E₂DH activity estimated from the rate of conversion of tritiated estradiol (E₂) to estrone (E₁), in the presence of an excess amount of NAD, was 2.8 nmol of El formed/mg protein/h in proliferative endometrium and 22 in secretory endometrium. The estrogen sulfatase activity was estimated by measuring the rate of conversion of [³H]-estrone sulfate (E₁S) to E_l. The average value was 1.6 nmol/mg protein/h with no significant change in activity during the menstrual cycle. The sulfotrnsferase activity, estimated from the rate of conversion of [³H]-E₁ to [³H] -E₁S, in the presence of an excess amount of adenosine 3’-phosphate 5-phosphosulfate (PAPS) had an average value of 0.03 nmol/mg protein/h in the secretory endometrium but was not detectable in the proliferative phase.

Studies of subcellular distribution of these metabolic enzymes indicated that the activities of E₂DH and sulfatase were found to be membrane bound to various particulates in both epithelial glands and stromal cells, while sulfotransferase activity was found only in the soluble fraction of the epithelial glands of the secretory endometrium. The K_m value of E₂DH and sulfatase are in the order of 10⁻⁶ M while sulfotransferase is 5×10⁻⁹ M. The relatively small K_m value of sulfo?transferase indicates that this enzyme may effectively compete the binding of estrogen to its receptor protein in the glandular epithelial cells of the secretory endometrium.

The estradiol metabolism in endometrial specimens was further analyzed at a low E₂ concentration in a superfusion system. It was found that intracellular E₂ concentration at the steady state of superfusion is inversely proportional to the summation of the rate of release of the metabolites, E₁, E₁S and estradiol-3-sulfate. This result indicates that the rate of metabolism in tissue will be the major regulating factor for the intracellular E₂ concentration.