title: Aryl hydrocarbon receptor activation in lactotropes and gonadotropes interferes with estradiol-dependent and -independent preprolactin, glycoprotein alpha and luteinizing hormone beta gene expression.
abstract: Arylhydrocarbon receptor (Ahr) activation by 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) interferes with female reproductive functions, but there is little information on the specific targets of TCDD in the hypothalamic-pituitary-gonadal (HPG) axis. In these studies, we found that TCDD upregulated known AhR target genes, cytochrome p450 1a1 (Cyp1a1), Cyp1a2 and Cyp1b1 in the rat pituitary gland. Moreover, 75% of pituitary lactotropes and 45% of gonadotropes contained Ahr mRNA, and most Ahr-containing cells were estrogen receptor 1 (Esr1)-positive. TCDD abrogated estradiol (E(2))-induced prolactin (Prl) expression in vivo and in vitro; conversely, E(2) blocked TCDD upregulation of luteinizing hormone beta (Lhb) and glycoprotein hormone alpha polypeptide (Cga) expression. TCDD had no effect on levels of Ahr mRNA, but upregulated Esr1 mRNA. E(2) independently repressed Ahr and Esr1 expression and blocked TCDD upregulation of Esr1. Thus, complex interactions between Ahr and Esr alter Prl and luteinizing hormone (LH) synthesis by direct actions in lactotropes and gonadotropes. These findings provide important insights into how TCDD disrupts female reproductive functions.
authors.affiliation: Molecular and Cellular Biology Graduate Program, 435 Morrill I North, University of Massachusetts Amherst, 637 North Pleasant Street, Amherst, MA 01003-9298, United States. jcao4@ncsu.edu
authors.forename: Jinyan
authors.initials: J
authors.lastname: Cao
authors.forename: Heather B
authors.initials: HB
authors.lastname: Patisaul
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Petersen
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D052681:Gonadotrophs / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D052682:Lactotrophs / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics* / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011388:Prolactin / Q000235:genetics* / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D015292:Glycoprotein Hormones, alpha Subunit; D037101:Luteinizing Hormone, beta Subunit; D000072317:Polychlorinated Dibenzodioxins; D011498:Protein Precursors; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D004958:Estradiol; C017671:preprolactin; D011388:Prolactin; D001189:Aryl Hydrocarbon Hydroxylases; C585499:Cyp1b1 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1