title: Acute Influences of Bisphenol A Exposure on Hypothalamic Release of Gonadotropin-Releasing Hormone and Kisspeptin in Female Rhesus Monkeys.
abstract: Bisphenol A (BPA) is an industrial compound with pervasive distribution in the environments of industrialized countries. The U.S. Centers for Disease Control recently found that greater than 90% of Americans carry detectable levels of BPA, raising concern over the direct influences of this compound on human physiology. Epidemiologic evidence links elevated BPA serum concentrations to human reproductive dysfunction, although controlled studies on the acute effect of BPA exposure on reproductive function are limited, particularly in primates. We evaluated the effect of direct BPA exposure on female primate hypothalamic peptide release. Specifically, using a microdialysis method, we examined the effects of BPA (0.1, 1, and 10nM) directly infused to the stalk-median eminence on the release of GnRH and kisspeptin (KP) in mid to late pubertal ovarian intact female rhesus monkeys. We found that the highest level of BPA exposure (10nM) suppressed both GnRH and KP release, whereas BPA at lower concentrations (0.1 and 1nM) had no apparent effects. In addition, we measured BPA in plasma and hypothalamic dialysates after an iv bolus injection of BPA (100 μg/kg). We found a relatively stable distribution of BPA between the blood and brain (plasma:brain ≅ 5:1) persists across a wide range of blood BPA concentrations (1-620 ng/mL). Findings of this study suggest that persistent, high-level exposures to BPA could impair female reproductive function by directly influencing hypothalamic neuroendocrine function.
authors: Wisconsin National Primate Research Center (J.R.K., K.L.K., B.P.K., J.P.G., E.T.), and Department of Pediatrics (E.T.), University of Wisconsin-Madison, Madison, Wisconsin 53715; Wisconsin State Laboratory of Hygeine (C.J.H.), Madison, Wisconsin 53718; and Southern Illinois University School of Medicine (J.R.K.), Springfield, Illinois 62794.
authors: Joseph R
authors: JR
authors: Kurian
authors: Wisconsin National Primate Research Center (J.R.K., K.L.K., B.P.K., J.P.G., E.T.), and Department of Pediatrics (E.T.), University of Wisconsin-Madison, Madison, Wisconsin 53715; Wisconsin State Laboratory of Hygeine (C.J.H.), Madison, Wisconsin 53718; and Southern Illinois University School of Medicine (J.R.K.), Springfield, Illinois 62794.
authors: Kim L
authors: KL
authors: Keen
authors: Wisconsin National Primate Research Center (J.R.K., K.L.K., B.P.K., J.P.G., E.T.), and Department of Pediatrics (E.T.), University of Wisconsin-Madison, Madison, Wisconsin 53715; Wisconsin State Laboratory of Hygeine (C.J.H.), Madison, Wisconsin 53718; and Southern Illinois University School of Medicine (J.R.K.), Springfield, Illinois 62794.
authors: Brian P
authors: BP
authors: Kenealy
authors: Wisconsin National Primate Research Center (J.R.K., K.L.K., B.P.K., J.P.G., E.T.), and Department of Pediatrics (E.T.), University of Wisconsin-Madison, Madison, Wisconsin 53715; Wisconsin State Laboratory of Hygeine (C.J.H.), Madison, Wisconsin 53718; and Southern Illinois University School of Medicine (J.R.K.), Springfield, Illinois 62794.
authors: James P
authors: JP
authors: Garcia
authors: Wisconsin National Primate Research Center (J.R.K., K.L.K., B.P.K., J.P.G., E.T.), and Department of Pediatrics (E.T.), University of Wisconsin-Madison, Madison, Wisconsin 53715; Wisconsin State Laboratory of Hygeine (C.J.H.), Madison, Wisconsin 53718; and Southern Illinois University School of Medicine (J.R.K.), Springfield, Illinois 62794.
authors: Curtis J
authors: CJ
authors: Hedman
authors: Wisconsin National Primate Research Center (J.R.K., K.L.K., B.P.K., J.P.G., E.T.), and Department of Pediatrics (E.T.), University of Wisconsin-Madison, Madison, Wisconsin 53715; Wisconsin State Laboratory of Hygeine (C.J.H.), Madison, Wisconsin 53718; and Southern Illinois University School of Medicine (J.R.K.), Springfield, Illinois 62794.
authors: Ei
authors: E
authors: Terasawa
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000187:drug effects* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D059648:Kisspeptins / Q000187:drug effects* / Q000378:metabolism; D008253:Macaca mulatta; D008473:Median Eminence; D017551:Microdialysis; D010636:Phenols / Q000494:pharmacology*; D010902:Pituitary Gland; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D007987:Gonadotropin-Releasing Hormone; D059648:Kisspeptins; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds