Biology of Reproduction, Vol 13, 482-489, Copyright © 1975 by Society for the Study of Reproduction

Prostaglandin E₁ Specific Binding in Human Myometrium

¹ Fertility Research, The Upjohn Company, Kalamazoo, Michigan

The equilibrium binding constant and the concentration of specific prostaglandin (PG)E₁ binding sites was determined in the low speed supernatant fraction of human myometrial homogenates. The apparent dissociation constant for 7 different preparations was 2.38 ± 0.38 x 10^-9M. PGE₁ specific binding site concentration did not appear to vary during the menstrual cycle. The relative affinity of various prostaglandins, PGE₁ metabolites and non-prostaglandin compounds for ³H-PGE₁ binding sites in human myometrium was determined. The relative affinities were: for the natural prostaglandins, PGE₁ PGE₂ >PGF₂ >PGB₂ PGA₁ PGA₂ >PGB₁ >PGD₂; for the PGE₁ metabolites, PGE₁>13,14-dihydro-PGE₁>13,14-dihydro-15-keto-PGE₁>15-keto-PGE₁. The prostaglandin precursors arachidonic acid and bis-homo--linolenic acid exhibited <0.1 binding inhibition relative to PGE₁ (= 100) at 10µg/ml. The following compounds did not inhibit ³H-PGE₁ binding at levels of 10 µg/ml or less: indomethacin, 7-oxa-13-prostynoic acid, cholesterol, progesterone and estradiol-17. The competition of 15-methyl-PGE₂ and 15-methyl-PGF₂ analogs for ³H-PGE₁ binding sites in human myometrium was determined in the in vitro assay. The relative affinities rank the compounds as: (15S)-15-methyl PGE₂>PGE₁PGE₂>(15S)-15-methyl PGE₂ methyl ester>PGF₂>(15S)-15-methyl PGF₂ THAM>(15S)-15-methyl PGF₂, methyl ester. These results were compared with the relative uterine stimulating potency of several natural prostaglandins and the 15-methylated prostaglandin analogs in the rhesus monkey in vivo.