4.6 Article

Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro

期刊

TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 253, 期 3, 页码 161-169

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2011.04.007

关键词

Methoxychlor; Steroid hormones; Steroidogenic enzymes; Metabolic enzymes; Antral follicles; Ovary

资金

  1. National Institutes of Health (NIH) [R01ES012893, R01ES019178]
  2. UIUC
  3. Eli Lilly Fellowship
  4. Billie A. Field Fellowship

向作者/读者索取更多资源

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 (E-2) 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 E-2 metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E-2, testosterone, androstenedione, and progesterone (P-4) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17 beta-hydroxysteroid dehydrogenase I (Hsd17b1), 17 alpha-hydroxylase/17,20-lyase (Cyp17a1), 3 beta 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. (C) 2011 Elsevier Inc. All rights reserved.

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