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Abstract

The binding of [3H]progesterone and [3H] 16 alpha,17 alpha-cycloalkanoprogesterones to proteins from rat, rabbit, and human uteri and other organs was studied. We found that 16 alpha,17 alpha-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] 16 alpha,17 alpha-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 16 alpha,17 alpha-cycloalkanoprogesterones and exhibits submicromolar Kd values for these steroids and a very low affinity for progesterone. We speculated that the introduction of a bulky substituent adjacently to the 17 beta-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.

Pregna-D′-pentaranes, Progestins and Antiprogestins: II. Pathways and Realization Mechanisms of Separate Biological Functions of Steroid Hormones

“…It turned out that the method of competitive binding could lead to erroneous results due to sorption on glass of the highly hydrophobic compounds under study (Table 1) [5]. The reliable results were obtained by the newly developed method of tritium introduction into ( V ) and then into other compounds under study; subsequently, the direct binding of ligands with PR was determined.…”

“…The reliable results were obtained by the newly developed method of tritium introduction into ( V ) and then into other compounds under study; subsequently, the direct binding of ligands with PR was determined. The use of labeled ligands in all cases and the application of quartz tubes treated with albumin led to reliable results [5,6].…”

“…The studies showed that, in all the cases, the formation of ligand-receptor complex proceeds as a twophase process [7,8] and leads to the formation of two complexes that differ in the dissociation rate ( Table 2). The formation rate and, probably, the rate of conversion of a rapidly dissociating complex into a slowly destructing complex approximately coincide with the hydrophobicity degree of ligand (Fig.…”

“…At the same time, the pentaranes hydrogenated in ring A, isomeric 16 α ,17 α -cyclohexano-5 α -( VI ) and 16 α ,17 α -cyclohexano-5 β -dihydroprogesterones ( VII ), analogues of 5 α -and 5 β -dihydroprogesterones ( VIII ) and ( IX ), the nearest metabolites of the native hormone, showed [12] an extremely low affinity to PR. This fact indicates that the mechanism of their antihormonal action is independent of the classical blockage of progesterone receptor.…”

“…In addition to the receptors, some representatives of the pregna-D'-pentarane series exhibited affinity to other two proteins, which we named pentaranofilins [11,13,14]. One of them was found in rat uterus, and another, in rat blood.…”