Uteroglobin (UG) is a rabbit uterine secretory protein whose synthesis can be induced by progestin administration. In an attempt to develop an in vitro system which would offer many advantages to the study of the molecular mechanism of action of steroid hormones, optimal conditions were determined for progesterone regulation of UG in primary cultures of rabbit endometrial epithelial cell lines. Progesterone (10-8 M) had a stimulatory effect on UG production by cultured endometrial epithelial cells derived from either estrous animals or animals 2 days after injection of hCG. The stimulatory effect of progesterone was more evident when the cultured cells were obtained from 2 days post-hCG animals and this effect was observed only when progesterone was present from the time of cell plating. The effect of progesterone on UG production was dose dependent. Lower doses (10-10 M) had an inhibitory effect while 10 -8 M progesterone had a stimulatory effect. This progesterone effect was unaffected by increasing the concentration of amino acids in the culture media and was greater when cells were plated at lower densities. Estradiol (10-10 M) per se had an inhibitory effect on UG production by cultured cells from 2 days post-hCG animals during the first day of culture. However, if the cells were exposed to the same concentration of estradiol alone or together with progesterone (10-8 M) for the first day of culture, the stimulatory effect of progesterone on UG production in the second day of culture was enhanced significantly. Therefore, it appears that progesterone and estradiol both play a role in regulating UG production by cultured endometrial cells. The concentration of progesterone as well as the presence of either ovarian steroid hormone in the media at the very beginning of the cell culture are critical for the stimulatory progesterone effect.
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