Progestin receptors in human uterine cytosol.
Progestin(norethindrone and norethindrone acetate)-binding protein, exhibiting characteristics similar to uterine progesterone receptor, has been identified in human uterine cytosol. The progestin receptor was characterized by sedimentation coefficient, 4.2 S; Stokes radius, 39 A; frictional ratio, 1.29; isoelectric pH, 4.6; molecular radius, 2.7 nm; and molecular weight in the range 67 000--74 000. The ammonium-sulfate-precipitated progestin-receptor complex was eluted from a DEAE-cellulose column at 0.18 M KCl. The progestin binding was saturable and stereospecific. The sequential variation in receptor concentration (early proliferative, 3800--4300 sites/cell; late proliferative, 9500--11 200 sites/cell; early secretory, 4900--6200 sites/cell; late secretory, 1800--2300 sites/cell) was in conformity for progesterone and the progestins, when concurrently measured. Oral administration of norethindrone significantly reduced the cytoplasmic and nuclear receptor concentration for estradiol and progesterone. A significant observation was that the progestins stabilized the receptor by forming a slowly dissociating complex with a t 1/2 approximately 110--130 min as compared with the progesterone-receptor complex dissociating with t 1/2 approximately 41 min. Thus, the uterine progestin receptor recognizes progestins in general, although with a varying degree of affinity, and the altered rate constants could be of putative importance in determining the biological potency of the progestins.
D003600:Cytosol / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D008598:Menstruation; D009640:Norethindrone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000077563:Norethindrone Acetate; D011372:Progestins / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism*; D014599:Uterus / Q000648:ultrastructure*
D011372:Progestins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000077563:Norethindrone Acetate; D009640:Norethindrone