Abstract
Untreated maternal hypothyroidism (hypoT) has serious consequences in offspring development that may result from the effect on lactation of maternal metabolism dysfunction. We studied the effects of prolonged propylthiouracil (PTU)-induced hypoT (0.1% PTU in drinking water starting 8 days before mating until day 21 of pregnancy or for 30 days in virgin rats) on liver and mammary lipid metabolism and serum lipid concentrations. In virgins, hypoT reduced hepatic mRNAs associated with triglyceride (TG) and cholesterol synthesis (including fatty acid synthase and 3-hydroxy-3-methylglutaryl coenzyme A reductase), and induced lobuloalveolar mammary development. Pregnancy increased hepatic mRNAs associated with TG and cholesterol synthesis and uptake (including LDL receptor) and with lipid oxidation, such as acyl CoA oxidase. HypoT decreased mRNAs and the activity of proteins associated with TG synthesis, and mRNAs associated with cholesterol uptake and lipid oxidation. Pregnancy increased mammary mRNAs related to lipid oxidation and decreased cholesterol synthesis, whereas hypoT decreased mRNAs and activities of proteins associated with TG synthesis and decreased epithelial mammary tissue. Virgin and pregnant hypoT rats had increased circulating VLDL + LDL cholesterol. HypoT decreased circulating TGs 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.
Highlights
Untreated maternal hypothyroidism has serious consequences in offspring development that may result from the effect on lactation of maternal metabolism dysfunction
Effect of hypothyroidism on liver lipid metabolism in virgin and pregnant rats To evaluate the effects of thyroid hormone on lipogenic enzymes, mRNA abundance of Acetyl CoA carboxylase (ACC), FAS, and glycerol-3-phosphate acyltransferase (GPAT) was measured using semiquantitative RT-PCR of total RNA prepared from livers of virgin and pregnant rats
Because degradation of lipids is affected by altered thyroid states, we measured the mRNA concentrations of acyl CoA oxidase (ACO) and carnitine palmitoyl transferase (CPT), enzymes related to -oxidation
Summary
Untreated maternal hypothyroidism (hypoT) has serious consequences in offspring development that may result from the effect on lactation of maternal metabolism dysfunction. Experimental hypothyroidism (hypoT) induced by propylthiouracyl (PTU) treatment is characterized by the accumulation of plasma LDL cholesterol, and decreased VLDL and plasma TGs [7], generally reflecting reduced binding activity of the hepatic LDL receptor (LDLR), which can be normalized after substitution therapy with thyroid hormone [3, 8]. A linear correlation between maternal and fetal plasma TGs has been described that has an important implication in newborn weight [12, 13] It contributes to milk synthesis in preparation for lactation, providing circulating TG in the form of lipoprotein to the mammary gland (MG) for milk lipid synthesis [9].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
