Environmental endocrine disrupters dysregulate estrogen metabolism and Ca2+ homeostasis in fish and mammals via receptor-independent mechanisms.
Xenoestrogen endocrine disrupters (EDs) in the environment are thought to be responsible for a number of examples of sexual dysfunction that have recently been reported in several species. There is growing concern that these compounds may also cause abnormalities of the male reproductive tract and reduced spermatogenesis in man. Whilst some effects of EDs may be receptor-mediated, there is growing evidence that these compounds can exert potent effects in vivo by directly interacting with cellular enzyme targets. Here we report on, and review, the effects of alkylphenols and other EDs on two such enzymes: (1) sulfotransferases, which convert active estrogenic steroids to inactive steroid sulfates; and (2) Ca(2+)-ATPases, which are responsible for maintaining low, physiological, intracellular Ca(2+) concentrations. These enzymes are potently inhibited by EDs in both fish and mammalian species. The increased concentrations of active estrogens and the likely cytotoxic effects of elevated concentrations of intracellular Ca(2+) arising from these effects may underlie some of the endocrine disrupting potential of these widespread industrial pollutants.
School of Biosciences, University of Birmingham, Edgbaston, B15 2TT Birmingham, UK. c.j.kirk@bham.ac.uk
Christopher J
CJ
Kirk
Laura
L
Bottomley
Nicholas
N
Minican
Howard
H
Carpenter
Selena
S
Shaw
Navdeep
N
Kohli
Matthew
M
Winter
Edwin W
EW
Taylor
Rosemary H
RH
Waring
Francesco
F
Michelangeli
Robert M
RM
Harris
D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004703:Endocrine System / Q000187:drug effects*; D004781:Environmental Exposure; D004967:Estrogens / Q000378:metabolism* / Q000506:poisoning / Q000633:toxicity*; D005399:Fishes; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D010636:Phenols / Q000737:chemistry / Q000378:metabolism / Q000506:poisoning; D011960:Receptors, Estrogen / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism
D004967:Estrogens; D010636:Phenols; D011960:Receptors, Estrogen; D015238:Sulfotransferases; D000252:Calcium-Transporting ATPases; D002118:Calcium