title: Lack of anti-androgenic effects of equol on reproductive neuroendocrine function in the adult male rat.
abstract: Equol (EQ), a metabolite of the soy isoflavone daidzein, has well known estrogenic properties. Data from animal studies suggested that EQ may act also as an anti-androgen. However, data regarding how EQ may affect brain functions like the regulation of neuroendocrine activity and reproductive outcomes in adult male rats are still lacking. We therefore investigated the effects of EQ on sex-steroid regulated gene expression in the brain [medial preoptic area/anterior hypothalamus (MPOA/AH) and medial basal hypothalamus/median eminence (MBH/ME)], pituitary, and prostate as a reference androgen-dependent organ. Furthermore reproductive outcomes were evaluated. The anti-androgen flutamide (FLUT) served as reference compound. Male rats (n=12 per group) were treated by gavage for 5 days with either EQ (100 or 250 mg/kgBW/day), or FLUT 100 mg/kgBW/day. All vehicle- and EQ-treated males showed successful reproductive outcomes, whereas FLUT-exposed males had severe reproductive impairments resulted in infertility. FLUT decreased relative weights of prostate, seminal vesicles and epididymides, and increased serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone and 5α-dihydrotestosterone without altering prolactin levels, whereas EQ exerted opposite effects. Both EQ and FLUT decreased gonadotropin releasing hormone (GnRH) expression in the MPOA/AH. Only FLUT upregulated levels of GnRH receptor expression both in the MBH/ME and pituitary. While EQ downregulated the hypothalamic ERα and ERβ expressions, but FLUT did not. In the prostate, only FLUT upregulated both ERα and AR mRNA expression levels. Taken together, our findings are the first data that EQ did not induce anti-androgenic effects on brain, prostate and male reproductive parameters, however, estrogenic neuroendocrine and reproductive effects of EQ were observed.
authors.affiliation: Department of Biology, Faculty of Science, Mahasarakham University, Khamriang Sub-district, Kantarawichai District, Mahasarakham Province 44150, Thailand. Electronic address: panida.l@msu.ac.th.
authors.forename: Panida
authors.initials: P
authors.lastname: Loutchanwoot
authors.affiliation: Department of Biology, Faculty of Science, Mahasarakham University, Khamriang Sub-district, Kantarawichai District, Mahasarakham Province 44150, Thailand. Electronic address: prayook.s@msu.ac.th.
authors.forename: Prayook
authors.initials: P
authors.lastname: Srivilai
authors.affiliation: Department of Endocrinology, University Medical Center Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany. Electronic address: hubjarry@med.uni-goettingen.de.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Jarry
mesh_terms: D000726:Androgen Antagonists; D000818:Animals; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D060754:Equol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D005837:Genitalia, Male / Q000473:pathology; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000502:physiology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000097:blood / Q000494:pharmacology*; D009490:Neurosecretory Systems / Q000187:drug effects*; D009929:Organ Size; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012726:Sexual Behavior, Animal / Q000187:drug effects
chemical_list: D000726:Androgen Antagonists; D012739:Gonadal Steroid Hormones; D008996:Monoamine Oxidase Inhibitors; D012333:RNA, Messenger; D060754:Equol; D012313:RNA; D005485:Flutamide
keywords: Endocrine disruptor; Equol; Hypothalamic GnRH pulse generator; Prostate; Reproductive hormones; Reproductive outcomes; Sex-steroid regulated gene expression