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

Kudoh M, M Kudoh, Masafumi Kudoh, Susaki Y, Y Susaki, Yoko Susaki, Yukitaka Ideyama, Ideyama Y, Y Ideyama, Nanya T, Taiki Nanya, T Nanya, Masamichi Mori, Mori M, M Mori, H Shikama, Shikama H, Hisataka Shikama
The Journal of steroid biochemistry and molecular biology · 1997 · vol. 63(1-3) , pp. 75–80 · doi:10.1016/s0960-0760(97)00074-5 · PMID:9449208 · W2032098472
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The novel aromatase inhibitor YM511 was found to inhibit the growth of endometrial explants and decrease insulin-like growth factor-I gene expression in rats with experimental endometriosis.

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Abstract

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.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Enzyme Inhibitors Insulin-Like Growth Factor I Triazoles Animals Antineoplastic Agents, Hormonal Antineoplastic Agents, Hormonal Aromatase Inhibitors Endometriosis Endometriosis Endometrium Endometrium Endometrium Enzyme Inhibitors Female Gene Expression Gene Expression Insulin-Like Growth Factor I Insulin-Like Growth Factor I

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