Effects of Hypothyroidism on Mammary and Liver Lipid Metabolism in Virgin and Late Pregnant Rats.

HAPON MB,; VARAS SM,; JAHN GA,; GIMENEZ MS.

JLR PAPERS IN PRESS

ASBMB The American Society for Biochemistry and Molecular Biology

Lugar: Bethesda, MD, USA; Año: 2005 vol. 46 p. 1320 - 1330

0022-2275

Untreated maternal hypothyroidism (hypoT) has serious consequences in offspring development that may be consequence of maternal metabolism dysfunctions affecting lactation. We studied the effects of prolonged PTU-induced hypoT (0.1% PTU in drinking water starting 8 days before mating until day 21 of pregnancy or during 30 days on virgin rats), on liver and mammary lipid metabolism and serum lipid concentrations. In virgins, hypoT reduced hepatic mRNAs associated with triglyceride and cholesterol synthesis (including fatty acid synthase and HMGCoAR), and induced lobuloalveolar mammary development. Pregnancy increased hepatic mRNAs associated with triglyceride and cholesterol synthesis and uptake (including LDL receptor) and to lipid oxidation, such as AcylCoA Oxidase; hypoT decreased mRNAs and activity of proteins associated with triglyceride synthesis and mRNAs associated with cholesterol uptake and lipid oxidation. Pregnancy increased mammary mRNAs related to lipid oxidation and decreased cholesterol synthesis, while hypoT decreased mRNAs and activities of proteins associated with triglyceride synthesis and decreased epithelial mammary tissue. Virgin and pregnant hypoT rats had increased circulating [VLDL+LDL]-cholesterol. HypoT decreased circulating triglycerides in pregnant rats. The observed effects of hypoT may result in decreased mammary lipid availability. This, along with the decreased epithelial mammary tissue during lactogenesis may contribute to the future lactational deficit of hypoT mothers.