title: In vivo and in vitro estrogenic activity of the antidepressant fluoxetine.
abstract: Recent years have seen an increase in the use of antidepressant drugs, especially fluoxetine (FLX), in sensitive populations, such as pregnant and lactating women. Although some evidence suggests a possible endocrine action of FLX, no specific studies have been performed to investigate this hypothesis. In the present study, we investigated the possible (anti)androgenic and (anti)estrogenic actions of FLX using Hershberger, uterotrophic (0.4, 1.7, and 17mg/kg), and reporter gene (7.6-129μM) assays. In the Hershberger assay, no differences were observed in androgen-dependent organ weights. However, the uterotrophic and gene reporter assays indicated a possible estrogenic action of FLX. Uterine weight increased in the 1.7 and 17mg/kg/day groups in the 3-day uterotrophic assay in immature rats. Additionally, noncytotoxic concentrations of FLX induced estrogenic responses and increased the estrogenic response of estradiol in MCF-7 breast cancer cells transfected with luciferase.
authors.affiliation: Department of Pharmacology, Federal University of Paraná, P.O. Box 19031, CEP 81531-990 Curitiba, PR, Brazil.
authors.forename: Juliane C
authors.initials: JC
authors.lastname: Müller
authors.forename: Pedro H
authors.initials: PH
authors.lastname: Imazaki
authors.forename: Ana C
authors.initials: AC
authors.lastname: Boareto
authors.forename: Emerson L B
authors.initials: EL
authors.lastname: Lourenço
authors.forename: Munisa
authors.initials: M
authors.lastname: Golin
authors.forename: Marina F
authors.initials: MF
authors.lastname: Vechi
authors.forename: Natália F
authors.initials: NF
authors.lastname: Lombardi
authors.forename: Bruna C
authors.initials: BC
authors.lastname: Minatovicz
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Scippo
authors.forename: Anderson J
authors.initials: AJ
authors.lastname: Martino-Andrade
authors.forename: Paulo R
authors.initials: PR
authors.lastname: Dalsenter
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000633:toxicity*; D045744:Cell Line, Tumor; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D005473:Fluoxetine / Q000633:toxicity*; D005837:Genitalia, Male / Q000033:anatomy & histology / Q000187:drug effects; D006801:Humans; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects* / Q000473:pathology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D004968:Estrogens, Non-Steroidal; D011960:Receptors, Estrogen; D005473:Fluoxetine