TY - JOUR
T1 - Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro
AU - Basavarajappa, Mallikarjuna S.
AU - Craig, Zelieann R.
AU - Hernández-Ochoa, Isabel
AU - Paulose, Tessie
AU - Leslie, Traci C.
AU - Flaws, Jodi A.
N1 - Funding Information:
This work was supported by the National Institutes of Health (NIH) [R01ES012893 (JAF) and R01ES019178 (JAF)], an Environmental Toxicology Fellowship from the Interdisciplinary Environmental Toxicology Program at UIUC (MSB), an Eli Lilly Fellowship in Toxicology/Pharmacology for graduate students (TP), and a Billie A. Field Fellowship in Reproductive Biology (ZRC).
PY - 2011/6/15
Y1 - 2011/6/15
N2 - 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 24h for 96h. 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.
AB - 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 24h for 96h. 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.
KW - Antral follicles
KW - Metabolic enzymes
KW - Methoxychlor
KW - Ovary
KW - Steroid hormones
KW - Steroidogenic enzymes
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U2 - 10.1016/j.taap.2011.04.007
DO - 10.1016/j.taap.2011.04.007
M3 - Article
C2 - 21514315
AN - SCOPUS:79956310493
SN - 0041-008X
VL - 253
SP - 161
EP - 169
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 3
ER -