title: Effects of the estrogen receptor antagonist fulvestrant on F344 rat prolactinoma models.
abstract: The relationship between estrogen and prolactinoma is well documented. But the anti-tumor effects of a pure estrogen receptor antagonist fulvestrant on prolactinomas, especially in vivo, and the possible mechanisms are still unclear. Therefore, the aim of this study was to evaluate the effects of fulvestrant and the involvement of the Wnt signaling pathway on rat prolactinoma models. Forty female F344 rat prolactinoma models were established by subcutaneous administration of 10 mg 17β-estradiol for 6 weeks. Rats were intramuscularly injected with fulvestrant (0, 0.5, 3, 20, 40 mg/kg), and tumor size, weight and serum prolactin (PRL) levels were evaluated before and after fulvestrant treatment at 3, 7 and 14 days. Expression of estrogen receptor α (ERα), β-catenin and Wnt inhibitory factor-1 (WIF-1) in prolactinomas was measured using quantitative PCR and western blotting, and methylation of the WIF-1 promoter was investigated using pyrosequencing. Tumor size, weight and serum PRL levels were inhibited in dose-dependent and time-dependent manners after fulvestrant treatments. β-catenin expression was downregulated but WIF-1 expression was upregulated following fulvestrant treatment. The methylation of the CpG site of the WIF-1 promoter was negatively correlated to the expression of WIF-1. In addition, the anti-cell proliferation of fulvestrant on GH3 cells was partly disrupted by Wnt signaling pathway agonist SB 216763. In conclusion, fulvestrant inhibited tumor proliferation and PRL secretion of prolactinomas via ERα, and the Wnt signaling pathway was involved in this anti-tumor effect. Therefore, fulvestrant may be a potential new drug for prolactinomas.
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, 6 Tiantan Xili, Beijing, 100050, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.forename: Hua
authors.initials: H
authors.lastname: Gao
authors.forename: Songbai
authors.initials: S
authors.lastname: Gui
authors.forename: Giwei
authors.initials: G
authors.lastname: Bai
authors.forename: Runchun
authors.initials: R
authors.lastname: Lu
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Yazhuo
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D019175:DNA Methylation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000008:administration & dosage; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D000077267:Fulvestrant; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000097:blood / Q000188:drug therapy*; D011388:Prolactin / Q000097:blood; D015175:Prolactinoma / Q000097:blood / Q000188:drug therapy*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D004967:Estrogens; D016326:Extracellular Matrix Proteins; D007211:Indoles; D036341:Intercellular Signaling Peptides and Proteins; D008301:Maleimides; C417521:SB 216763; C521045:Wif1 protein, rat; D000077267:Fulvestrant; D004958:Estradiol; D011388:Prolactin