Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro
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{sub 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{sub 2} metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E{sub 2}, testosterone, androstenedione, and progesterone (P{sub 4}) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17{beta}-hydroxysteroid dehydrogenase 1 (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. - Highlights: > MXC inhibits steroidogenesis > MXC inhibits steroidogenic enzymes > MXC induces metabolic enzymes
- OSTI ID:
- 21587762
- Journal Information:
- Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 253; ISSN TXAPA9; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANDROGENS
ANDROSTANES
ANDROSTENEDIONE
ANIMALS
BIOASSAY
BODY
CHOLESTEROL
DMSO
ENZYME IMMUNOASSAY
ENZYMES
ESTRADIOL
ESTRANES
ESTROGENS
FEMALE GENITALS
FEMALES
GONADS
HORMONES
HYDROXY COMPOUNDS
HYDROXYLASES
HYPOTHESIS
IMMUNOASSAY
IN VITRO
KETONES
MAMMALS
MESSENGER-RNA
METABOLISM
MICE
NUCLEIC ACIDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OVARIES
OXIDOREDUCTASES
PESTICIDES
PREGNANES
PROGESTERONE
PROTEINS
RNA
RODENTS
SEX
STEROID HORMONES
STEROIDS
STEROLS
SULFOXIDES
TESTOSTERONE
VERTEBRATES