title: Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro.
abstract: The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E₂) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24 h for 96 h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E₂ metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E₂, testosterone, androstenedione, and progesterone (P₄) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17β-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17α-hydroxylase/17,20-lyase (Cyp17a1), 3β hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels.
authors.affiliation: Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
authors.forename: Mallikarjuna S
authors.initials: MS
authors.lastname: Basavarajappa
authors.forename: Zelieann R
authors.initials: ZR
authors.lastname: Craig
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernández-Ochoa
authors.forename: Tessie
authors.initials: T
authors.lastname: Paulose
authors.forename: Traci C
authors.initials: TC
authors.lastname: Leslie
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Flaws
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000032:analysis; D000818:Animals; D001141:Aromatase / Q000032:analysis; D002478:Cells, Cultured; D004958:Estradiol / Q000032:analysis* / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D007306:Insecticides / Q000633:toxicity*; D008731:Methoxychlor / Q000633:toxicity*; D051379:Mice; D006080:Ovarian Follicle / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D010750:Phosphoproteins / Q000502:physiology; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D012739:Gonadal Steroid Hormones; D007306:Insecticides; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D001141:Aromatase; D008731:Methoxychlor