Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Estrogen-driven Prolactin-mediated Gene Expression Networks Hormone Induced Prostatic Dysplasia

ABSTRACT: Emerging evidence suggests that estrogen and prolactin (PRL) play a key role in prostate cancer development, yet their relationship and molecular actions in prostate is not well understood. To address this issue, we made the first direct comparison of estrogen and PRL actions in the Noble rat (NBL) prostate dysplasia model. Prostatic dysplasia in lateral prostate (DLP) has been induced by elevated circulating levels of estrogen and PRL in NBL with estrogen (E2)-filled implants, while physiological level of testosterone (T) was maintained with T-filled implants. The effect of estrogen and PRL was studied by using ICI and bromocriptine (Br) as their respective blockers, both can effectively inhibited dysplasia development under T+E2 induction. Transcript expression profile of the four treatment groups (Control, T+E2, T+E2+Br, and T+E2+ICI) has been characterized in this array.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Johannes Freudenberg

PROVIDER: E-GEOD-17819 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Research resource: estrogen-driven prolactin-mediated gene-expression networks in hormone-induced prostatic intraepithelial neoplasia.

Tam Neville N C NN Szeto Carol Y Y CY Freudenberg Johannes M JM Fullenkamp Amy N AN Medvedovic Mario M Ho Shuk-Mei SM

Molecular endocrinology (Baltimore, Md.) 20100922 11

Cotreatment with testosterone (T) and 17β-estradiol (E2) is an established regimen for inducing of prostatic intraepithelial neoplasia (PIN) and prostate cancer in rodent models. We previously used the pure antiestrogen ICI 182,780 (ICI) and bromocriptine, a dopamine receptor agonist, to inhibit PIN induction and systemic hyperprolactinemia in Noble rats and found that the carcinogenic action of T+E2 is mediated directly by the effects of E2 on the prostate and/or indirectly via E2-induced hyper ...[more]

PMID: 20861223

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Project description:Synchrony between embryo competency and uterine receptivity is essential for a successful implantation. Mice with ablation of COUP-TFII in the uterus (PRCre/+;COUP-TFIIflox/flox), exhibit implantation defects and increased ER activity in the luminal epithelium, suggesting the high ER activity may disrupt the window of uterine receptivity. In order to determine if the increased ER activity in PRCre/+;COUP-TFIIflox/flox mutant is the cause of the defective implantation, we inhibited of ER activity in order to rescue the implantation defect in mutant mice. ICI 182,780 (ICI), a pure ER antagonist, was administered to PRCre/+;COUP-TFIIflox/flox mutant and COUP-TFIIflox/flox control mice during receptive period and the number of implantation sites were examined. COUP-TFIIflox/flox control mice treated with oil or ICI showed the normal number of implantation sites. As expected no implantation sites were observed in PRCre/+;COUP-TFIIflox/flox mutant mice treated with oil, consistent with previous observation. However, implantation sites were detected, albeit at a reduced number in comparison to the control in PRCre/+;COUP-TFIIflox/flox mutant mice upon ICI treatment.. ICI treatment was also able to rescue the expression of WNT4 and BMP2, genes important for endometrial decidualization in the PRCre/+;COUP-TFIIflox/flox mutant mice. To ensure the rescue of embryo attachment and decidualization is a consequence of a reduction of estrogen receptor activity with ICI treatment of the mutants, we examined the expression of ER target gene, such as lactoferrin, in PRCre/+;COUP-TFIIflox/flox mutant mice. Having shown that ICI could rescue the implantation and decidualization defects of the PRCre/+;COUP-TFIIflox/flox mutant mice, the ability of ICI treatment to rescue pregnancy in these mice was assayed. While mice were born in COUP-TFIIflox/flox control mice given ICI, no pups were born in the PRCre/+;COUP-TFIIflox/flox mutant mice, with the loss in pregnancy in the PRCre/+;COUP-TFIIflox/flox mutant mice treated with ICI being due to defects in placentation. These results demonstrate that during the peri implantation period, COUP-TFIIâs role in regulating embryo attachment and decidualiton is through the reduction of ER activity. However COUP-TFII expression is still required in the post implantation period to facilitate placentation. Experiment Overall Design: Murine uteri were isolated at 6 hour after oil or ICI 182,780 injection for RNA extraction and hybridization on Affymetrix microarrays. To do this mice were ovariectomized and treated hormones (estrogen and progesterone) to mimic the early pregnant condition.

Dataset Information

Estrogen-driven Prolactin-mediated Gene Expression Networks Hormone Induced Prostatic Dysplasia

Publications

Research resource: estrogen-driven prolactin-mediated gene-expression networks in hormone-induced prostatic intraepithelial neoplasia.

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