Search

An organ culture system was used to evaluate the response of human proliferative endometrium to progesterone stimulation. The glycogen content of proliferative tissue was increased as much as thirteenfold during organ culture in media containing progesterone. The steroid-induced increase in tissue glycogen was detectable after 16 hours and reached a maximum at 48 and 72 hours of culture. Progesterone induced a significant increase in glycogen at a media concentration of 1.6 × 10−6M and a maximal increase at 3.2 × 10−7to 3.2 × 10−6M. At higher media concentrations of progesterone (1.6 × 10−5M), glycogen levels failed to reach the maximum obtainable. The extent of the response correlated poorly with the initial glycogen content of the tissue and not at all with the initial content of high-affinity progesterone-binding sites in cytosol. Addition of estradiol-17β to medium (10−10M to 10−7) had no effect on the progesterone-induced increase in tissue glycogen. Delaying the addition of progesterone to the cultures for 24 hours resulted in a diminished glycogen response; the reduced response may be related to a rapid decrease in high-affinity progesterone-binding sites as measured in cytosol prepared from tissues cultured in the absence of progesterone. High-affinity progesterone-binding sites in endometrial cytosol were found to decrease rapidly during the first 24 hours of culture. The addition of cycloheximide or actinomycin D to the culture media inhibited the increase in tissue glycogen caused by progesterone. These results demonstrate that progesterone can induce an in vitro response in human proliferative endometrium similar to that seen in vivo. The response of the endometrium is reproducible and allows for comparisons between grouped data obtained by using tissues from several different donors.

The relative potency of six commonly used synthetic progestins has been evaluated in an organ culture system for human endometrium. The affinities of these progestins for endometrial progesterone receptor were also evaluated after removing the CBG-like protein by spheroidal hydroxylapatite chromatography. All six progestins induced an increase in tissue glycogen during culture at lower concentrations than did progesterone; only one (medroxyprogesterone acetate) had a relative affinity greater than progesterone. The relative potencies and affinities of the synthetic progestins were found to have the same relative order but to differ in relative magnitude.