title: Neonatal xenoestrogen exposure alters growth hormone-dependent liver proteins and genes in adult female rats.
abstract: The hypothalamic-growth hormone (GH)-liver axis represents a new concept in endocrine regulation of drug toxicity. Preponderant sex differences are found in liver gene expression, mostly dependent on the sexually dimorphic pattern of GH secretion which is set during the neonatal period by gonadal steroids. We tested if GH-dependent sexually dimorphic liver enzymes and proteins was perturbed by neonatal Bisphenol A (BPA) treatment in female rats. Female rats were sc injected with BPA (50 or 500 μg/50 μl) or castor oil vehicle from postnatal day 1 to 10. At five months serum prolactin, pituitary GH, and serum and liver insulin growth factor-I (IGF-I) were measured by RIA. Major urinary proteins (MUPs) were determined by electrophoresis. Liver Cyp2c11, Cyp2c12, Adh1, Hnf6, and Prlr mRNA levels were determined by real time PCR. Pituitary GH content and liver IGF-I concentration were increased by neonatal BPA treatment, indicating partial masculinization of the GH axis in treated females. GH-dependent female predominant liver enzyme genes (Cyp2c12 and Adh1) and a transcription factor (Hnf6) were downregulated or defeminized, while there were no changes in a male predominant gene (Cyp2c11) or protein (MUP). Our findings indicate that perinatal exposure to BPA may compromise the sexually dimorphic capacity of the liver to metabolize drugs and steroids.
authors: Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina.
authors: Maria Cecilia
authors: MC
authors: Ramirez
authors: Nadia Soledad
authors: NS
authors: Bourguignon
authors: Maria Marta
authors: MM
authors: Bonaventura
authors: Victoria
authors: V
authors: Lux-Lantos
authors: Carlos
authors: C
authors: Libertun
authors: Damasia
authors: D
authors: Becu-Villalobos
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001559:Benzhydryl Compounds; D000072467:Cytochrome P450 Family 2; D004334:Drug Administration Schedule; D004591:Electrophoresis, Polyacrylamide Gel; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D013006:Growth Hormone / Q000378:metabolism*; D051559:Hepatocyte Nuclear Factor 6 / Q000235:genetics; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011981:Receptors, Prolactin / Q000235:genetics; D012727:Sex Characteristics; D012737:Sex Factors; D039181:Steroid 16-alpha-Hydroxylase / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics; D000098826:Bisphenol A Compounds
chemical_list: D000426:Alcohol Dehydrogenase; D001189:Aryl Hydrocarbon Hydroxylases; D001559:Benzhydryl Compounds; D000072467:Cytochrome P450 Family 2; D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D013006:Growth Hormone; D051559:Hepatocyte Nuclear Factor 6; D007334:Insulin-Like Growth Factor I; D010636:Phenols; D011388:Prolactin; D012333:RNA, Messenger; D011981:Receptors, Prolactin; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases; C496607:Onecut1 protein, rat; C548904:insulin-like growth factor-1, rat; C450279:CYP2C11 protein, rat; C034694:steroid 15-beta-hydroxylase; C006780:bisphenol A; D000098826:Bisphenol A Compounds