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Abstract

Role of systemic and local IGF-I in the effects of estrogen on growth and epithelial proliferation of mouse uterus (PDF) (HTML) 
Sato,Tomomi; Wang,Gui-Min; Hardy,Matthew P.; Kurita,Takeshi; Cunha,Gerald R.; Cooke,Paul S.
Endocrinology 143(7): 2673-2679
Publication date: 2002

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IGF-I is a critical regulator of uterine growth, and locallyproduced uterine IGF-I could mediate the effects of 17ß-E2on growth and cellular proliferation. We used IGF-I knockout(KO) mice and tissue grafting to determine the roles of localand systemic IGF-I in uterine growth and E2 responsiveness.Uteri from adult KO mice and neonatal and adult wild-type (WT)mice were grown under the renal capsule of female athymic micefor 4 wk. Initial uterine weights of adult KO and neonatal WTmice were 5% or less of those of adult WT uteri. Weights ofadult WT uterine grafts did not increase during grafting. Weightsof adult KO and neonatal WT uteri exposed to normal systemiclevels of IGF-I in athymic hosts increased 20- to 30-fold toequal or exceed those of adult WT grafts. Uterine epithelialheight, reduced in KO mice, was restored to WT levels in KOuteri grafted into athymic hosts. The absence of local IGF-Iproduction in KO uteri did not impair E2- induced epithelialproliferation in KO uterine grafts. Neonatal WT uteri graftedinto KO hosts showed minimal growth, providing evidence thatlocal uterine IGF-I production is insufficient to support uterinegrowth in the absence of systemic IGF-I. E2 treatment of KOfemales produced minimal uterine growth, confirming that lackof IGF-I, rather than E2, caused the uterine hypoplasia. Insummary, systemic IGF-I supports normal uterine growth and E2response in the absence of local IGF-I. Local IGF-I is not adirect mediator of E2 action in uterus, and systemic IGF-I maybe more important than previously thought for growth of theuterus and other tissues.

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