Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals.
Within the last decade, several classes of chemicals have been shown in laboratory studies to disrupt reproductive development by acting as androgen receptor (AR) antagonists and/or inhibitors of fetal Leydig cell testosterone production. Some phthalate esters alter gubernacular differentiation by reducing insulin-like 3 (insl3) mRNA levels. We have found that AR antagonists and inhibitors of fetal testis hormone production generally induce cumulative, apparently dose-additive adverse effects when administered in mixtures. New research has also revealed the presence of androgens in the environment. Effluents from pulp and paper mills display androgenic activity of sufficient potency to masculinize and/or sex-reverse female fish. Effluent from beef cattle concentrated animal feedlot operations from the United States also displays androgenic activity in vitro, due, in part, to the presence of a steroid used to promote growth in beef cattle. In summary, we are only beginning to identify the classes of chemicals that have the potential to alter the androgen signalling pathway in utero. This review will (i) present information on the classes of environmental chemicals that display antiandrogenic and androgenic activities in vitro and in vivo, and (ii) provide an insight into how exposure to mixtures these chemicals might behave in utero.
Gray
L Earl
LE
MD-72, Endocrinology Branch, Reproductive Toxicology Division, NHEERL, ORD, US Environmental Protection Agency, RTP, NC 27771, USA. gray.earl@epa.gov
Wilson
Vickie S
VS
Stoker
Tammy
T
Lambright
Christy
C
Furr
Johnathan
J
Noriega
Nigel
N
Howdeshell
Kembra
K
Ankley
Gerald T
GT
Guillette
Louis
L
D000726:Androgen Antagonists / Q000494:pharmacology / Q000633:toxicity*; D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D004781:Environmental Exposure; D005260:Female; D008297:Male; D010575:Pesticides / Q000494:pharmacology / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D012733:Sex Differentiation / Q000187:drug effects / Q000502:physiology; D015262:Xenobiotics / Q000494:pharmacology / Q000633:toxicity*
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000728:Androgens; D010575:Pesticides; D011944:Receptors, Androgen; D015262:Xenobiotics