title: Differential stimulation pathways of progesterone secretion from newly formed corpora lutea in rats treated with ethylene glycol monomethyl ether, sulpiride, or atrazine.
abstract: Ethylene glycol monomethyl ether (EGME), sulpiride, and atrazine are known ovarian toxicants, which increase progesterone (P4) secretion and induce luteal cell hypertrophy following repeated administration. The aim of this study was to define the pathways by which these compounds exerted their effects on the ovary and hypothalamic-pituitary-gonadal (HPG) axis. In the ovary, changes in the steroidogenic activity of new and old corpora lutea (CL) were addressed. EGME (300 mg/kg), sulpiride (100 mg/kg), or atrazine (300 mg/kg) were orally given daily for four times from proestrus to diestrus in normal cycling rats. Treatment with all chemicals significantly increased serum P4 levels, and EGME as well as sulpiride induced increases in prolactin (PRL) levels. In new CL, at both the gene and the protein levels, all three chemicals upregulated the following steroidogenic factors: scavenger receptor class B type I, steroidogenic acute regulatory protein, P450 cholesterol side-chain cleavage, and 3β-hydroxysteroid dehydrogenase (HSD) and downregulated the luteolytic gene, 20α-HSD. Coadministration of EGME and bromocriptine, a D2 agonist, completely inhibited PRL but not P4 secretion. Additionally, steroidogenic factor expression levels were upregulated, and 20α-HSD level was downregulated in new CL. These results suggest that EGME both directly and indirectly stimulates P4 production in luteal cells, whereas sulpiride elevates P4 through activation of PRL secretion in the pituitary. Atrazine may directly activate new CL by stimulating steroidogenic factor expressions. The present study suggests that multiple pathways mediate the effects of EGME, sulpiride, and atrazine on the HPG axis and luteal P4 production in female rats in vivo.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Taketa
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inoue
authors.forename: Miwa
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Gen
authors.initials: G
authors.lastname: Watanabe
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Taya
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D043607:20-alpha-Hydroxysteroid Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001280:Atrazine / Q000633:toxicity*; D001971:Bromocriptine / Q000633:toxicity; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005026:Ethylene Glycols / Q000633:toxicity*; D005260:Female; D007150:Immunohistochemistry; D008184:Luteal Cells / Q000187:drug effects*; D042282:Microdissection / Q000379:methods; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000097:blood / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013469:Sulpiride / Q000633:toxicity*; D015854:Up-Regulation; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D018955:CD36 Antigens; D005026:Ethylene Glycols; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D001971:Bromocriptine; D011374:Progesterone; D013469:Sulpiride; D011388:Prolactin; D015067:17-Hydroxysteroid Dehydrogenases; D043607:20-alpha-Hydroxysteroid Dehydrogenase; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D002786:Cholesterol Side-Chain Cleavage Enzyme; C005219:methyl cellosolve; D001280:Atrazine