Inhibitory effects of a novel aromatase inhibitor, YM511, on growth of endometrial explants and insulin-like growth factor-I gene expression in rats with experimental endometriosis.
Estrogen deprivation therapy effectively prevents progress of endometriosis but the precise mechanism by which estrogen stimulates growth of endometriotic implants is still unknown. We examined effects of hypoestrogenic state induced by ovariectomy, gonadotropin-releasing hormone agonist (leuprolide) or aromatase inhibitor (YM511), on growth of experimental endometrial explant, a section of endometrium transplanted under the renal capsule, in rats. Ovariectomy gradually reduced the volume of endometrial explants for 21 days. YM511 (0.1 mg/kg) and leuprolide (1 mg/rat) completely reduced volume of endometrial explants but they differed widely in the onset of inhibitory action. YM511 prevented growth of explants on day 4 but leuprolide had no inhibitory effect until day 15. YM511 dose-dependently reduced volume of endometrial explants and its minimum effective dose was 0.04 mg/kg. Insulin-like growth factor-I (IGF-I) mRNA expression in endometrial explant and uterus was examined on day 4. YM511 decreased IGF-I expression in endometrial explant and uterus by 58% and 48%, respectively. Reductions of the extent of IGF-I expression by YM511 and ovariectomy were comparable. A significant correlation between the volume and IGF-I mRNA expression in endometrial explant suggests that local expression of this gene may play an important role in stimulating growth of endometrial explants.
Kudoh
M
M
Metabolic Diseases Research, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan.
Susaki
Y
Y
Ideyama
Y
Y
Nanya
T
T
Mori
M
M
Shikama
H
H
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D047072:Aromatase Inhibitors; D004715:Endometriosis / Q000235:genetics / Q000517:prevention & control*; D004717:Endometrium / Q000187:drug effects* / Q000254:growth & development / Q000637:transplantation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000187:drug effects* / Q000235:genetics; D016729:Leuprolide / Q000494:pharmacology; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D014230:Triazoles; C096486:YM 511; D007334:Insulin-Like Growth Factor I; D016729:Leuprolide