| Autor: |
D'souza, Anil, Hinduja, Indira, Kodali, Sandhya, Moudgil, V., Puri, Chander |
| Zdroj: |
Molecular & Cellular Biochemistry; Oct1994, Vol. 139 Issue 1, p83-90, 8p |
| Abstrakt: |
We have undertaken characterization of binding of the newly synthesized progesterone receptor (PR) antagonist ZK98299 in the cellular fractions of human myometrium. Specific [H]progesterone and [H]ZK98299 binding was observed in the cytosol and the nuclear fractions, and could be competitively replaced by either of the steroids in their radioinert form. Although PR occupied by both steroids exhibited nuclear uptake, the extent of nuclear binding was lower with [H]ZK98299-receptor complexes. The binding of both ligands to PR was a function of the duration of incubation and the protein concentration: it was saturable at 3-6 nM steroids with a dissociation constant of approximately 2 nM. However, the number of ZK98299 binding sites (72 fmoles/mg protein) was lower compared to that of progesterone (322 fmoles/mg protein). The relative binding affinity (RBA) of ZK98299 for the nuclear PR was about 33% that of progesterone. The results of our study suggest that ZK98299 binds to PR in the cytosol and the nuclear fractions. The antiprogestin effects of ZK98299 reported in the literature are PR-mediated and may result from suboptimal nuclear binding/retention of antiprogestin-receptor complexes. Since this study did not involve isolation and study of individual PR isoforms, PR-A and PR-B, the present data should be viewed as representing an average of contributions by the two receptor forms. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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