| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 1998 Oxford University Press
research-article |
Dose-Response Examination of UDP-Glucuronosyltransferase Inducers and Their Ability to Increase both TGF-ß Expression and Thyroid Follicular Cell Apoptosis1
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center Kansas City, Kansas 66160
Received January 7, 1998; accepted May 29, 1998
Exposure to certain microsomal enzyme inducers that increase UDP-glucuronosyltransferase (UDP-GT) activity decreases thyroid hormone levels, which may lead to a subsequent increase in thyroid-stimulating hormone (TSH). This elevation of serum TSH has many effects on the thyroid, including increasing thyroid follicular cell proliferation, leading to hyperplasia. While induction of UDP-GT activity decreases thyroid hormone levels by enhancing biotransformation and subsequent biliary secretion, only certain UDP-GT inducers exhibit the ability to increase serum TSH levels. For example, phenobarbital (PB) and pregnenolone-16
-carbonitrile (PCN) increase serum levels of TSH, while 3-methylcholanthrene (3MC) and Aroclor 1254 (PCB) do not. Increased serum TSH concentration also enhances thyroid gland expression of TGF-ß1, an anti-proliferative, pro-apoptotic protein. In a previous study in our laboratory, rats were treated for various times (up to 90 days) with PB and PCN, which increased TGF-ß1 protein and apoptosis. The present study was designed to examine the dose-response effect of TSH-increasing (PB and PCN) and nonincreasing (3MC and PCB) UDP-GT inducers on apoptosis and TGF-ß1. PB and PCN, UDP-GT inducing compounds which increase serum TSH, increased the percentage of TGF-ß1-positive follicular cells and increased apoptosis. In contrast, UDP-GT inducers that did not increase TSH (3MC and PCB) did not alter cell death or TGF-ß production. These data suggest that the increase of TGF-ß by TSH may serve to regulate the growth of hyperplastic thyroid.
Key Words: apoptosis; thyroid; phenobarbital (PB); pregnenolone-16-carbonitrile (PCN); 3-methylcholanthrene (3-MC); Aroclor 1254 (PCB); and TGF-ß1.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. S. Roegge, V. C. Wang, B. E. Powers, A. Y. Klintsova, S. Villareal, W. T. Greenough, and S. L. Schantz Motor Impairment in Rats Exposed to PCBs and Methylmercury during Early Development Toxicol. Sci., February 1, 2004; 77(2): 315 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. T. Zoeller, A. L. S. Dowling, and A. A. Vas Developmental Exposure to Polychlorinated Biphenyls Exerts Thyroid Hormone-Like Effects on the Expression of RC3/Neurogranin and Myelin Basic Protein Messenger Ribonucleic Acids in the Developing Rat Brain Endocrinology, January 1, 2000; 141(1): 181 - 189. [Abstract] [Full Text] [PDF]
|
|