Estradiol and 20α-Dihydroprogesterone Dehydrogenase Activities in Human Endometrium During the Menstrual Cycle

Abstract

Estradiol dehydrogenase (E 2 -DH) and20<x-dihydroprogesterone dehydrogenase (20aDHP-DH) activities in human endometrium at various phases of the menstrual cycle were measured by incubating 3 H-estradiol (E 2 ) or 3 H-20a-dihydroprogesterone (20aDHP) with an 800 X g supernatant of tissue and excess NAD + . The enzymatic activities, expressed as nmoles of product formed per hr and per mg of protein, showed a significant increase during the secretory phase. The average values of E 2 -DH activities were 1.2 in proliferative endometrium and 14 in secretory tissue. The corresponding 20aDHP-DH activities were lower (0.3 and 3.0). The total amount of E 2 receptors in endometrium, determined by the method of superfusion, was found to decline from 3.2 pmole/mg DNA in the proliferative phase to 0.6 pmole/mg DNA at the end of the secretory phase. The increase in E 2 -DH levels leads to a faster removal of E 2 from endometrium since the conversion of E 2 to E x is only partially reversible and E 1 rather than E 2 is released by the tissue. The concomitant decline of intracellular levels of E 2 and E 2 receptor during the secretory phase can be expected to result in a diminished effect of circulating estrogens on endometrium. (Endocrinology 94: 419, 1974) P REVIOUS studies on the uptake and metabolism of labeled estradiol (E 2 ) and estrone (E x ) by super fused slices of human endometrium revealed differences in the rates of interconversion between these estrogens in tissues obtained at various phases of the menstrual cycle (1). On the basis of a knowledge of the dynamics of E x and E 2 in human endometrium (2), the observed variations of the steady state concentrations of labeled E x and E 2 in the perfusion medium and in the tissue were interpreted to indicate an increase of the E 2 dehydrogenase (E 2 -DH) activity during the secretory phase. The purpose of the present study was to measure directly this enzymatic activity in human endometrium at various phases of the menstrual cycle, using a tracer kinetic method. The 20a-dihydroprogesterone dehydrogenase (20aDHP-DH) activity was measured concurrently, using a similar method. Both enzymatic activities were found to be much higher in the secretory than in the proliferative phase. The elevation of these enzymatic activities after ovulation con-

Estrogen and Progesterone Binding Proteins in Normal Human Myometrium and Leiomyoma Tissue

“…This observation is supported by the comparison of the sedimentation patterns of nucleus-bound steroid hormone receptors from normal myometrium in the middle proliferative and early secretory phases and from leiomyoma, and by kinetics of steroid hormone transfer from the cytoplasm to the nucleus under equilibrium conditions. (29,30) and our group (10) on human endometrium have shown, is subject to the inductive effect of the progesterone receptor mechanism. One can only speculate on the cause and pathophysiological significance of the differences in progesterone receptor contents of normal myometrium and leiomyoma: Since, as animal experiments have shown, the progesterone receptor is induced via the estradiol receptor mechanism, and thus represents an end product of the chain of estradiol action, it can be inferred that an alteration at one of the steps sur> sequent to the translpeation of the estradiol receptor (transcription, processing, translation) leads to the "progesterone receptor defect".…”

“…The result is that the estradiol receptor mechanism, which is responsible for both its own induction and that of the progesterone receptor, is blocked (10,29,30).…”

In Vitro Conversion of Estradiol-17β into Estrone in Normal Human Myometrium und Leiomyoma

“…Measurement of the 170-hydroxysteroid dehydrogenase activity in .the myometrium of fertile women revealed periodic changes correlated with the menstrual cycle. The values were low during the proliferation phase, rose shaiply to the point of ovulation, and reached a maximum during the early secretory phase, Such drastic changes in the 17j3-hydroxysteroid dehydrogenase activity during the menstrual cycle were first observed by Tseng & Gurpide (20) in human endometrium, and were later confirmed by Follow et al (7) for human endometrium and mammary tissue. The dramatic increase in the enzyme activity is presumably related to the postovulatory flood of progesterone into the myometrium cell after the development of the corpus luteum, and may thus be induced via the progesterone receptor mechanism.…”

“…These may change the state of equilibrium between estradiol and estrone to some extent, though from studies on the human placental 17/J-hydroxysteroid dehydrogenase (24,25) it has been shown that under physiological conditions the equilibrium of the reaction lies on the side of estrone. Furthermore it has been shown by supervision experiments with human endometrium (20)(21)(22), that estrone (in contrast to estradiol) is not accumulated in the target cell. This observation seems all the more important since estrone is known to compete for specific estradiol receptor and enzyme binding-sites.…”

“…an increase in enzyme activity is observed in vitro and in vivo after estrogen pretreatment followed by progesterone application (this can be blocked by inhibitors of protein synthesis); 2. there is a positive correlation between microsomal 17/J-hydroxysteroid dehydrogenase activity and progesterone receptor concentration; and 3. endometrial carcinomas only react to high-dose gestagen therapy with an increase in their 170-hydroxysteroid dehydrogenase activity if they possess adequate levels of progesterone receptors. For human myometrium there is less substantial evidence for a progesterone induced synthesis of the 17β-hydroxysteroid dehydrogenase than for human endometrium (20)(21)(22)(23). Other causes for a postovulatory increase of enzyme activity in human myometrium therefore have to be taken into consideration, such as intracellular proton concentration or the redox state…”