Effects of estrogen, progesterone, and methoxychlor on surgically induced endometriosis in rats.
Endometriosis is a disease of women where endometrial tissue is found growing at ectopic sites. While evidence suggesting a role for the ovarian hormones in endometriosis exists, no complete studies of the roles of estrogen and progesterone have heretofore been performed. Also, if estrogen has a role in the growth and/or maintenance of endometriosis, it is likely that the proestrogenic pesticide, methoxychlor (MXC), might also have such an effect. Sixty rats underwent surgery on Day 0 to induce endometriosis. On Day 21, all rats were ovariectomized. During surgery, the diameters of all endometriotic implants (which were fully developed) were measured. Starting on Day 21, groups of rats were treated daily, for 3 weeks, with (a) vehicle (b) estrone, 1 micrograms/rat, E;(c) progesterone, 2 mg/rat, P; (d) E + P, 1 micrograms + 2 mg; (e) MXC, 250 mg/kg; or (f) MXC + P, 250 mg/kg + 2 mg/rat. On Day 42, all rats were killed, and the diameters of all endometriotic sites were measured. While no differences in diameter were found across groups prior to ovariectomy, ovariectomy plus treatment altered the growth of endometriosis tissue. Progesterone and vehicle treatments produced results that were identical: regression of endometriotic sites. Both estrogen and MXC treatments maintained endometriotic site size at a level greater than that in the vehicle-treated group. The combination of progesterone with either estrone or MXC did not alter the effect of either chemical. We conclude that while estrogen promotes the growth of endometriosis, progesterone either produces regression or fails to maintain the sites. MXC, at a relatively high dose, supports the development of endometriosis. Concurrent progesterone treatment does not modulate the effects of estrone or MXC. These results suggest that exposure of women to high doses of MXC may exacerbate the development of endometriosis or contribute to its recurrence.
Developmental Toxicology Division, HERL, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
A M
AM
Cummings
J L
JL
Metcalf
D000818:Animals; D004715:Endometriosis / Q000139:chemically induced / Q000473:pathology*; D004970:Estrone / Q000633:toxicity*; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D008731:Methoxychlor / Q000633:toxicity*; D010052:Ovariectomy; D011374:Progesterone / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007306:Insecticides; D004970:Estrone; D011374:Progesterone; D008731:Methoxychlor