正常子宮と子宮内膜癌におけるEstrogen ReceptorとProgesterone Receptorの生化学的性質の特異性について
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In this study, human uterine endometrial estrogen receptor (ER) and progesterone receptor (PR) in normal menstrual cycle were estimated, and biochemical characterization of ER and PR in normal endometrium and endometrial carcinoma were also investigated.<BR>Following results were obtained in this study.<BR>1) In normal menstrual cycle, ER and PR levels in endometrial cytosol gradually rose to peaks in the late proliferative phase, but PR in nuclear fraction rose to a peak in the early secretory phase.<BR>2) Scatchard analysis of ER in normal endometrium and myometrium contains two estradiol (E<SUB>2</SUB>) binding sites with dissociation constants (Kd) of 10<SUP>-9</SUP>M and 10-<SUB>-10</SUB>, but endometrial carcinoma contains a single population of E<SUB>2</SUB> binding site with Kd's 10-<SUB>-10</SUB>.<BR>3) Total binding sites for ER and PR of normal endometrium have 2 3 times much more than those of endometrial carcinoma.<BR>4) In normal endometrium, specific binding of 40nM <SUP>3</SUP> HE<SUB>2</SUB> on isoelectric focusing (IEF) indicated three binding activities with elution pH's (EPH) of 4, 6 and 8. But specific binding of 2 nM 3 HE<SUB>2</SUB> indicated only one binding activity with EPH of 6 in endometrial carcinoma. 5) Specific binding of EPH 6 indicated high affinity ER (type 1 ER) and specific binding of EPH 8 indicated low affinity ER (type 2 ER) in the result of IEF and Scatchard analysis. Loss of type 2 receptor is important result in endometrial carcinoma.<BR>The above results suggest that increase in blood E<SUB>2</SUB> level increases endometrial ER and PR, and increase in blood progesterone level after ovulation decreases endometrial ER and PR for anti-ER and PR effect of progesterone. If type 2 ER could transport hormone receptor complex to the nucleus, loss of type 2 ER would be the important cause of ER and PR decrease and get resistance of hormone therapy to endometrial carcinoma.
- 一般社団法人 日本内分泌学会の論文
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- 正常子宮と子宮内膜癌におけるEstrogen ReceptorとProgesterone Receptorの生化学的性質の特異性について