Estrogen and selective estrogen receptor modulator regulation of insulin-like growth factor binding protein 5 in the rat uterus

Insulin-like growth factor (IGF) binding protein 5 (IGFPB-5) is abundant in the uterus and is implicated in the sex steroid-induced growth of this tissue. The purpose of this study was to investigate the potential for modulation of the action of IGFPB-5 at the uterus level in the rat by estrogen and selective estrogen receptor modulators (SERMs). One hundred and twenty adult rats, 2-3 months of age, were included. Among them 100 animals were ovariectomized 4 days prior to the use of drugs for 48 days. Rats were divided into six groups: non-ovariectomized (group 1); ovariectomized (group 2); and those receiving conjugated equine estrogens, 50 microg/day (group 3), tamoxifen 250 microg/day (group 4), raloxifene 3 mg/kg (group 5) and toremifene 2.5 mg/kg (group 6). Total RNA was isolated from the uterus and IGFBP-5 mRNA levels were assessed by the semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Our results demonstrate that conjugated equine estrogens were able to up-regulate mRNA levels of the IGFBP-5 gene, while oophorectomy alone as well as associated with hormone therapy such as tamoxifen, raloxifene and toremifene resulted in down-regulation of uterine IGFBP-5 gene expression. The up-regulation of IGFBP-5 expression induced by estrogens suggests that, in vivo, the uterotrophic effects of estrogen replacement therapy are mediated, at least inpart, by the IGF pathways. On the other hand, the use of SERMs (tamoxifen, raloxifene and toremifene) was associated with severe down-regulation of this gene at the transcription level.