Our purpose was to examine the roles of natural (
estradiol (E2) and
estrone (E1)) and
synthetic estrogens (
ethinyl estradiol (EE),
moxestrol (MOX), and tamoxifene (TAM)) in regulating production of
sex hormone-binding globulin (SHBG) by human
hepatoma G2 (Hep G2) cells, the rationale being that
synthetic estrogens are less rapidly metabolized than natural
estrogens and, thus, may alter SHBG levels more readily. In Hep G2 cells, E2, E1, and EE
at 10(-7) M did not result in significantly greater SHBG secretion compared to control cells. The
synthetic estrogens, MOX and TAM, caused significant, P < 0.001, increases of 30% and 51% in SHBG secretion
at 10(-7) M compared to controls. However, when TAM and E2 were added together, each
at 10(-7) M, no increase in SHBG secretion was noted. We conclude that natural
estrogens at physiologic concentrations do not increase SHBG secretion by Hep G2 cells, but the increase of SHBG secretion caused by MOX and TAM suggests that the lack of effect of E2 and E1 may, in part, be due to their rapid metabolism. In addition, TAM stimulates SHBG secretion by interaction with the genome that is different, in certain respects, from that of E2.