title: Effects of progesterone and norethindrone on female fathead minnow (Pimephales promelas) steroidogenesis.
abstract: As knowledge of contaminants capable of adversely modulating endocrine functions increases, attention is focused on the effects of synthetic progestins as environmental endocrine disrupters. In the present study, effects of exposure to a synthetic progestin (norethindrone, 168 ± 7.5 ng/L) and endogenous progestogen (progesterone, 34 ± 4.1 ng/L) on steroidogenesis in adult female fathead minnows were examined. In vivo exposure to either compound lowered expression (nonsignificant) of luteinizing hormone (LHβ) levels in the brain along with significantly down-regulating the beta isoform of membrane progesterone receptor (mPRβ) in ovary tissue. The correspondence between lowered LHβ levels in the brain and mPRβ in the ovary is suggestive of a possible functional association as positive correlations between LHβ and mPR levels have been demonstrated in other fish species. In vitro exposure of ovary tissue to progesterone resulted in significantly elevated progestogen (pregnenolone, 17α-hydroxyprogesterone, and 17α,20β-dihydroxypregnenone) and androgen (testosterone) production. Whereas in vitro exposure to norethindrone did not significantly impact steroid hormone production but showed decreased testosterone production relative to solvent control (however this was not significant). Overall, this study showed that exposure to a natural progestogen (progesterone) and synthetic progestin (norethindrone), was capable of modulating LHβ (in brain) and mPRβ expression (in ovary).
authors.affiliation: Department of Biology, Institute of Applied Science, University of North Texas, Denton, Texas, USA; Wildlife International, Evans Analytical Group, Easton, Maryland, USA.
authors.forename: Lene H
authors.initials: LH
authors.lastname: Petersen
authors.forename: David
authors.initials: D
authors.lastname: Hala
authors.forename: Dennis
authors.initials: D
authors.lastname: Carty
authors.forename: Mark
authors.initials: M
authors.lastname: Cantu
authors.forename: Dalma
authors.initials: D
authors.lastname: Martinović
authors.forename: Duane B
authors.initials: DB
authors.lastname: Huggett
mesh_terms: D000818:Animals; D003530:Cyprinidae / Q000235:genetics / Q000378:metabolism*; D005260:Female; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics / Q000378:metabolism; D009640:Norethindrone / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D014867:Water / Q000737:chemistry
chemical_list: D037201:Follicle Stimulating Hormone, beta Subunit; D037101:Luteinizing Hormone, beta Subunit; D011980:Receptors, Progesterone; D013256:Steroids; D014867:Water; D011374:Progesterone; D009640:Norethindrone
keywords: Aquatic toxicology; Endocrine disruptors; Pharmaceuticals; Steroidogenesis