Uterotrophic

Rodent 3-day uterotrophic assay increase in uterine weight in ovariectomised rat. 

STAR trial (Study of tamoxifen and raloxifene), which was completed in 2006, demonstrated additional utility of raloxifene in the prevention and treatment of breast cancer. In fact, the absence of associated uterotrophic effects with raloxifene suggests that it may be a safer agent than tamoxifen for use as a chemopreventative in high-risk postmenopausal women [3] therefore, raloxifene has very recently become a new option for breast cancer prevention now available for physicians and their patients. 

Gellert, R.J. (1978). Uterotrophic activity of polychlorinated biphenyls (PCB) and induction of precocious reproductive aging in neonatally treated female rats. Environmental Research 16, 123-130. 

Picherit et al., 2001 7 month old OVX adult rats 3 doses of isoflavone extract (20, 40, 80 mg/kg body wt/d) for 91 d Isoflavones reversed femoral failure load, total femoral, diphyseal or metaphyseal BMDs and normalized bone turnover markers induced by OVX. Optimal dose without uterotrophic effect was 40 mg/kg body wt... 

Bazedoxifene has also demonstrated in experimental studies its ability to inhibit the growth of ER(+) tumors in mice and rats in the absence of uterotrophic effects (Greenberger et al. 2001). At the present time bazedoxifene s ability to counteract the estrogenic effects of CEE at the levels of both breast and endometrium is being tested in a multicentric study comparing calcium + vitamin D to bazedoxifene with and without a low dose of CEE in mild symptomatic postmenopausal women. 

Ashby J, Odum J, Foster JR (1997) Activity of raloxifene in immature and ovariectomized rat uterotrophic assays. Regul Toxicol Pharmacol 25(3) 226-231... 

Carthew P, Edwards RE, Nolan BM (1999) Uterotrophic effects of tamoxifen, toremifene, and raloxifene do not predict endometrial cell proliferation in the ovariectomized CD 1 mouse. Toxicol Appl Pharmacol 158(l) 24-32... 

Huynh H, Poliak M (1994) Uterotrophic actions of estradiol and tamoxifen are associated with inhibition of uterine insulin-like growth factor binding protein 3 gene expression. Cancer Res 54(12) 3115—3119... 

Kunimatsu T, Yamada T, Ose K et al (2002) Lack of (anti-)androgenic or estrogenic effects of three pyrethroids (esfenvalerate, fenvalerate, and permethrin) in the Hershberger and uterotrophic assays. Regul Toxicol Pharmacol 35 227-237... 

Stob M, Baldwin RS, Tuite J, Andrews FN, Gillette KG (1962) Isolation of an anabolic uterotrophic compound from com infected with Gibberella zeae. Nature 196 1318-1320... 

BPA was also tested in the uterotrophic test for estrogenicity at doses ranging from 200 to 800 mg kg-1 body weight. BPA was effective in increasing the wet uterine weight, confirming previous results. 

OECD, Guideline for testing of chemicals Inmature rat uterotrophic bioassay screening test, 1998. 

Makela, S., Savolainen, H., Aavik, E., et al. (1999). Differentiation between vasculoprotective and uterotrophic effects of ligands with different binding aflinities to estrogen a and P, Proc. Natl. Acad. Sci. U.S.A., 96, 7077-7082. 

Faber WD, Deyo JA, Stump DG, Navarro L, Ruble K, Knapp J (2007) Developmental toxicity and uterotrophic studies with di-2-ethyUiexyl therephthalate. Birth Defects Res B Dev Reprod Toxicol 80 396-405... 

Seinen W, Lemmen JG, Pieters RHH, Verbruggen EMJ, van der Burg B (1999) AHTN and HHCB show weak estrogenic - but no uterotrophic activity. Toxicol Lett 111 161-168... 

McKim JM, Wilga PC, Breslin WJ, Plotzke KP, Gallavan RH, Meeks RG (2001) Potential estrogenic and antiestrogenic activity of the cyclic siloxane octamethylcyclotetrasiloxane (D4) and the linear siloxane hexamethyldisiloxane (HMDS) in immature rats using the uterotrophic assay. Toxicol Sci 63 37-46... 

Newly proposed test guidelines to specifically address effects on hormone homeostasis and on male and female reproductive organs include the rodent uterotrophic assay to detect estrogenic effects (OECD 2007a) and the rodent Hershberger assay to detect androgenic effects (OECD 2007b). 

Steroidogenesis in vitro assay Uterotrophic assay Adult male assay... 

OECD. 2003h. Detailed background review of the uterotrophic assay. Summary of the available literature in support of the project of the OECD taskforce on endocrine disrupters testing and assessment (EDTA) to standardise and validate the uterotrophic assay. OECD Series on Testing and Assessment No. 38. Environment Directorate, Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology. ENV/JM/MONO(2003)1. Paris OECD. 

OECD. 2006a. OECD report of the initial work towards the validation of the rodent uterotrophic assay - Phase... 

OECD. 2007a. The uterotrophic bioassay in rodents A short-term screening test for oestrogenic properties. Draft OECD guideline for the testing of chemicals. Revised 23 January 2007. Paris OECD, http //www. oecd.org/dataoecd/48/55/37994719.doc... 

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