Species and Tissue Distribution of Proteins Binding 16α,17α-Cycloalkanoprogesterone Derivatives
Tóm tắt
The binding of [3H]progesterone and [3H]16α,17α-cycloalkanoprogesterones to proteins from rat, rabbit, and human uteri and other organs was studied. We found that 16α,17α-cycloalkanoprogesterone derivatives display affinities for the uterine progesterone receptors comparable with that of the natural hormone and no substantial species differences in the affinity. Rabbit uterus was found to have no proteins distinct from the progesterone receptor that specifically bind [3H]16α,17α-cycloalkanoprogesterones. At the same time, in the human uterus, we found another protein that binds some of these progesterone derivatives; it turned out to be similar to the protein from rat uterus. A similar protein with the same selectivity and affinity for steroids was also found in rat and human kidneys. Blood serum, liver, lung, and a number of other tissues were found to contain a protein of the third type that binds the same 16α,17α-cycloalkanoprogesterones and exhibits submicromolar K
d values for these steroids and a very low affinity for progesterone. We speculated that the introduction of a bulky substituent adjacently to the 17β-side chain of progesterone could result in a change in the general biodynamics of the derivative including its transport, uptake, and accumulation in tissues, which may determine the selectivity of its effect.
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