Tissue distribution and regulation of 5'-deiodinase processes in lactating rats

Thyroxine 5'-deiodinase (5'D) catalyses deiodination of the prohormone thyroxine (T4) to the metabolically active hormone 3,5,3'-tri-iodothyronine (T3). Previously, it has been demonstrated that rat mammary gland expresses a 5'D with enzymatic properties equivalent to those of the type I enzyme (5'D-I) found in rat liver and kidney. Using complementary DNA (cDNA) for rat hepatic 5'D-I, we have examined expression of 5'D-I messenger RNA (mRNA) in liver, and mammary gland from virgin and lactating rats, and in seven other tissues from virgin rats. 5'D-I mRNA could not be detected in mammary gland either by Northern blotting or by the more sensitive technique of reverse transcribing mRNA and then amplifying the cDNA by polymerase chain reaction (RT-PCR). Analysis of the seven tissues from virgin rats by RT-PCR showed 5'D-I amplicons in liver, kidney and thyroid. No amplicons were detected in adrenal gland, cardiac muscle, skeletal muscle or spleen. In addition, the effect of lactation intensity on circulating thyroid hormones, hepatic and mammary gland 5'D activity, and hepatic 5'D-I mRNA levels was examined. A strong inverse relationship was noted between increased lactation intensity (suckling burden) and circulating T4 and T3, hepatic 5'D-I activity and hepatic 5'D-I mRNA levels. Mammary gland 5'D activity was positively correlated to lactation intensity. The data presented strongly suggest that the 5'D activity expressed in lactating mammary gland is encoded by a mRNA different from the 5'D-I message found in rat liver, kidney and thyroid gland, and may help explain the differential regulation of 5'D-I activity in these organs during lactation. In addition, hepatic 5'D-I activity was found to be correlated with the concentration of 5'D-I mRNA, suggesting that regulation is pretranslational. Results are consistent with a previously suggested involvement of 5'D in establishing metabolic adaptations to support lactation.