title: Neonatal agonism of ERβ impairs male reproductive behavior and attractiveness.
abstract: The organization of the developing male rodent brain is profoundly influenced by endogenous steroids, most notably estrogen. This process may be disrupted by estrogenic endocrine disrupting compounds (EDCs) resulting in altered sex behavior and the capacity to attract a mate in adulthood. To better understand the relative role each estrogen receptor (ER) subtype (ERα and ERβ) plays in mediating these effects, we exposed male Long Evans rats to estradiol benzoate (EB, 10 μg), vehicle, or agonists specific for ERβ (DPN, 1 mg/kg) or ERα (PPT, 1 mg/kg) daily for the first four days of life, and then assessed adult male reproductive behavior and attractiveness via a partner preference paradigm. DPN had a greater adverse impact than PPT on reproductive behavior, suggesting a functional role for ERβ in the organization of these male-specific behaviors. Therefore the impact of neonatal ERβ agonism was further investigated by repeating the experiment using vehicle, EB and additional DPN doses (0.5 mg/kg, 1 mg/kg, and 2 mg/kg bw). Exposure to DPN suppressed male reproductive behavior and attractiveness in a dose dependent manner. Finally, males were exposed to EB or an environmentally relevant dose of genistein (GEN, 10 mg/kg), a naturally occurring xenoestrogen, which has a higher relative binding affinity for ERβ than ERα. Sexual performance was impaired by GEN but not attractiveness. In addition to suppressing reproductive behavior and attractiveness, EB exposure significantly lowered the testis to body weight ratio, and circulating testosterone levels. DPN and GEN exposure only impaired behavior, suggesting that disrupted androgen secretion does not underlie the impairment.
authors.affiliation: Department of Biology, North Carolina State University, Raleigh NC 27695, USA.
authors.forename: Alana W
authors.initials: AW
authors.lastname: Sullivan
authors.forename: Peter
authors.initials: P
authors.lastname: Hamilton
authors.forename: Heather B
authors.initials: HB
authors.lastname: Patisaul
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology; D008297:Male; D052586:Mating Preference, Animal / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D048789:Phytoestrogens / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012726:Sexual Behavior, Animal / Q000187:drug effects*
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D009570:Nitriles; D010636:Phenols; D048789:Phytoestrogens; D011422:Propionates; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; C074283:estradiol 3-benzoate; D004958:Estradiol; D019833:Genistein