Endocrine active compounds affect thyrotropin and thyroid hormone levels in serum as well as endpoints of thyroid hormone action in liver, heart and kidney.
To assess interference with endocrine regulation of the thyroid axis, rats (female, ovariectomised) were treated for 12 weeks with the suspected endocrine active compounds (EAC) or endocrine disrupters (ED) 4-nonylphenol (NP), octyl-methoxycinnamate (OMC) and 4-methylbenzylidene-camphor (4-MBC) as well as 17beta-estradiol (E2) and 5alpha-androstane-3beta,17beta-diol (Adiol) on the background of a soy-free or soy-containing diet, and endpoints relevant for regulation via the thyroid axis were measured. Thyrotropin (TSH) and thyroid hormone (T4, T3) serum levels were altered, but not in a way consistent with known mechanisms of feedback regulation of the thyroid axis. In the liver, malic enzyme (ME) activity was significantly increased by E2 and Adiol, slightly by OMC and MBC and decreased by soy, whereas type I 5'-deiodinase (5'DI) was decreased by all treatments. This may be due rather to the estrogenic effect of the ED, as there is no obvious correlation with T4 or T3 serum levels. None of the substances inhibited thyroid peroxidase (TPO) in vitro, except for NP. In general, several endocrine active compounds disrupt the endocrine feedback regulation of the thyroid axis. However, there was no uniform, obvious pattern in the effects of those ED tested, but each compound elicited its own spectrum of alterations, arguing for multiple targets of interference with the complex network of thyroid hormone action and metabolism.
Institut für Experimentelle Endokrinologie und Endokrinologisches Forschungszentrum EnForCé, Charité, Universitätsmedizin Berlin, Campus Mitte, Schumannstrasse 20/21, D-10117 Berlin, Germany.
Cornelia
C
Schmutzler
Inka
I
Hamann
Peter J
PJ
Hofmann
Gabor
G
Kovacs
Luise
L
Stemmler
Birgit
B
Mentrup
Lutz
L
Schomburg
Petra
P
Ambrugger
Annette
A
Grüters
Dana
D
Seidlova-Wuttke
Hubertus
H
Jarry
Wolfgang
W
Wuttke
Josef
J
Köhrle
D000818:Animals; D004702:Endocrine Glands / Q000187:drug effects*; D005260:Female; D006321:Heart / Q000187:drug effects*; D007453:Iodide Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D008291:Malate Dehydrogenase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000097:blood*; D013972:Thyrotropin / Q000097:blood*; D015262:Xenobiotics / Q000633:toxicity*
D013963:Thyroid Hormones; D015262:Xenobiotics; D013972:Thyrotropin; D008291:Malate Dehydrogenase; D007453:Iodide Peroxidase