Inhibition of testicular steroidogenesis by the xenoestrogen bisphenol A is associated with reduced pituitary luteinizing hormone secretion and decreased steroidogenic enzyme gene expression in rat Leydig cells.
Exposure of humans to bisphenol A (BPA), a monomer in polycarbonate plastics and a constituent of resins used in food packaging and dentistry, is significant. In this report exposure of rats to 2.4 microg/kg.d (a dose that approximates BPA levels in the environment) from postnatal d 21-35 suppressed serum LH (0.21 +/- 0.05 ng/ml; vs. control, 0.52 +/- 0.04; P < 0.01) and testosterone (T) levels (1.62 +/- 0.16 ng/ml; vs. control, 2.52 +/- 0.21; P < 0.05), in association with decreased LHbeta and increased estrogen receptor beta pituitary mRNA levels as measured by RT-PCR. Treatment of adult Leydig cells with 0.01 nm BPA decreased T biosynthesis by 25% as a result of decreased expression of the steroidogenic enzyme 17alpha-hydroxylase/17-20 lyase. BPA decreased serum 17beta-estradiol levels from 0.31 +/- 0.02 ng/ml (control) to 0.22 +/- 0.02, 0.19 +/- 0.02, and 0.23 +/- 0.03 ng/ml in rats exposed to 2.4 microg, 10 microg, or 100 mg/kg.d BPA, respectively, from 21-35 d of age (P < 0.05) due to its ability to inhibit Leydig cell aromatase activity. Exposures of pregnant and nursing dams, i.e. from gestation d 12 to postnatal d 21, decreased T levels in the testicular interstitial fluid from 420 +/- 34 (control) to 261 +/- 22 (P < 0.05) ng/ml in adulthood, implying that the perinatal period is a sensitive window of exposure to BPA. As BPA has been measured in several human populations, further studies are warranted to assess the effects of BPA on male fertility.
Akingbemi
Benson T
BT
Center for Biomedical Research, The Population Council, 1230 York Avenue, New York, NY 10021, USA.
Sottas
Chantal M
CM
Koulova
Anna I
AI
Klinefelter
Gary R
GR
Hardy
Matthew P
MP
D000375:Aging; D000728:Androgens / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D001559:Benzhydryl Compounds; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D047629:Estrogen Receptor beta; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007985:Leydig Cells / Q000187:drug effects / Q000201:enzymology*; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020318:Rats, Long-Evans; D011960:Receptors, Estrogen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012669:Seminal Vesicles / Q000254:growth & development; D013256:Steroids / Q000096:biosynthesis*; D013737:Testis / Q000196:embryology / Q000254:growth & development; D013739:Testosterone / Q000096:biosynthesis; D000098826:Bisphenol A Compounds
D000728:Androgens; D001141:Aromatase; D001559:Benzhydryl Compounds; D004958:Estradiol; D047629:Estrogen Receptor beta; D004968:Estrogens, Non-Steroidal; D007986:Luteinizing Hormone; D037101:Luteinizing Hormone, beta Subunit; D010636:Phenols; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013256:Steroids; D013739:Testosterone; C006780:bisphenol A; D000098826:Bisphenol A Compounds