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Title: METHIMAZOLE, THYROID HORMONE REPLACEMENT AND LIPOGENIC ENZYME GENE EXPRESSION IN BROILERS

Author
item Rosebrough, Robert
item Poch, Stephen
item Russell, Beverly
item Richards, Mark

Submitted to: Comparative Biochemistry and Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/27/2004
Publication Date: 1/31/2005
Citation: Rosebrough, R.W., Poch, S.M., Russell, B.A., Richards, M.P. 2005. Methimazole, thyroid hormone replacement and lipogenic enzyme gene expression in broilers. Comparative Biochemistry and Pysiology 139:189-194.

Interpretive Summary: Excess fat production in the modern broiler accounts for an annual loss to the poultry industry of 1000 to 1500 million dollars annually. The original source of this problem relates to selection genetic practices that emphasized rapid growth at the expense of other carcass characteristics. The literature is of limited value in determining methods to depress fat synthesis and allow lean tissue synthesis to remain at an elevated rate. The thyroid axis is more important in regulating intermediary metabolism in birds than in mammals because of a questionable role for insulin in birds. The purpose of this set of experiments was to 1) chemically inhibit thyroid hormone production and 2) examine protein nutritional status as a moderator of this inhibition. Although hypothyroidism decreased lipid synthesis in 28-day old chickens, restoration of thyroid function in these birds increased synthetic ability in market-age birds (49 days of age). Assigning a role to the thyroid hormone axis may be difficult because an interplay between protein nutrition and background thyroid status.

Technical Abstract: The purpose of this experiment was to determine the possible relationship between certain indices of lipid metabolism and specific gene expression in chickens fed methimazole to simulate hypothyroidism. Male, broiler chickens growing from 7 to 28 days of age were fed diets containing 18% crude protein and either 0 or 1 g methimazole per kg of diet. At 28 days, these two groups were further subdivided into groups receiving 18% crude protein diets containing either 0 or 1 mg triiodothyronine (T3) per kg. Birds were sampled from at 28, 30 and 33 days. Measurements taken included in vitro lipogenesis (IVL), malic enzyme (ME) activity, isocitrate dehydrogenase, aspartate amino transferase, the expression of the genes for ME, fatty acid synthase (FAS) and acetyl coenzyme carboxylase (ACC). Hypothyroidism decreased IVL and ME at 28 d of age; however, T3 supplementation for 2 d restored both IVL and ME. Paradoxically, continuing T3 replenishment for an additional 3d decreased IVL but did not decrease ME activity. In contrast, supplemental T3 decreased IVL in euthyroid birds, regardless of the dosing interval, but had no effect on ME activity. Although methimazole decreased ME gene expression, there was only a transitory relationship between enzyme activity and gene expression when plasma T3 was restored with exogenous T3. These data may help to explain some of the apparent reported dichotomies in lipid metabolism elicited by changes in the thyroid state of animals. In addition, most metabolic changes in response to feeding T3 occurred within 2 to 5 d, suggesting that changes in intermediary metabolism preceded morphological changes. In conclusion, the thyroid state of the animal will determine responses to exogenous T3.