title: Sex differences and the development of the rabbit brain: effects of vinclozolin.
abstract: The preoptic/anterior hypothalamic area (POA/AH) is one of the most sexually dimorphic areas of the vertebrate brain and plays a pivotal role in regulating male sexual behavior. Vinclozolin is a fungicide thought to be an environmental antiandrogen, which disrupts masculine sexual behavior when administered to rabbits during development. In this study, we examined several characteristics of the rabbit POA/AH for sexual dimorphism and endocrine disruption by vinclozolin. Pregnant rabbits were dosed orally with vinclozolin (10 mg/kg body weight) or carrot paste vehicle once daily for 6 wk beginning at midgestation and continuing through nursing until Postpartum Week 4. At 6 wk, offspring were perfused with 4% paraformaldehyde and brains processed for immunocytochemical localization of tyrosine hydroxylase, calbindin, gonadotropin-releasing hormone (GnRH), or Nissl stain. There were significant sex differences in the distribution of calbindin in the POA/AH and the size of cells in the dorsal POA/AH (values greater in females than in males), but not in the number or distribution of tyrosine hydroxylase or GnRH neurons. In both sexes, exposure to vinclozolin significantly increased calbindin expression in the ventral POA/AH and significantly decreased number of GnRH neurons selectively in the region of the organum vasculosum of the lamina terminalis (OVLT) but not more caudally in the POA/AH. This is the first documentation of a sexually dimorphic region in the rabbit brain, and further supports the use of this species as a model for studying the influence of vinclozolin on reproductive development with potential application to human systems.
authors.affiliation: Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.
authors.forename: Erin S
authors.initials: ES
authors.lastname: Bisenius
authors.forename: D N Rao
authors.initials: DN
authors.lastname: Veeramachaneni
authors.forename: Ginger E
authors.initials: GE
authors.lastname: Sammonds
authors.forename: Stuart
authors.initials: S
authors.lastname: Tobet
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development*; D001923:Brain Chemistry / Q000187:drug effects; D064026:Calbindins; D005260:Female; D005659:Fungicides, Industrial / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009490:Neurosecretory Systems / Q000254:growth & development / Q000502:physiology; D010080:Oxazoles / Q000494:pharmacology*; D011817:Rabbits; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012727:Sex Characteristics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; D064026:Calbindins; D005659:Fungicides, Industrial; D010080:Oxazoles; D064030:S100 Calcium Binding Protein G; D007987:Gonadotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase; C025643:vinclozolin