Regulation of mammary gland sensitivity to thyroid hormones during the transition from pregnancy to lactation

Thyroid hormones are galactopoietic and help to establish the mammary gland's metabolic priority during lactation. Expression patterns for genes that can alter tissue sensitivity to thyroid hormones and thyroid hormone activity were evaluated in the mammary gland and liver of cows at 53, 35, 20, and 7 days before expected parturition, and 14 and 90 days into the subsequent lactation. Transcript abundance for the three isoforms of iodothyronine deiodinase, type I (DIO1), type II (DIO2) and type III (DIO3), thyroid hormone receptors alphal (TR alpha 1), alpha2 (TR alpha 2) and betal (TR beta 1), and retinoic acid receptors alpha (RXR alpha) and gamma (RXR gamma), which act as coregulators of thyroid hormone receptor action, were evaluated by quantitative RT-PCR. The DIO3 is a 5-deiodinase that produces inactive iodothyronine metabolites, whereas DIO1 and DIO2 generate the active thyroid hormone, triiodothyronine, from the relatively inactive precursor, thyroxine. Low copy numbers of DIO3 transcripts were present in mammary gland and liver. DIO2 was the predominant isoform expressed in mammary gland and DIO1 was the predominant isoform expressed in liver. Quantity of DIO1 mRNA in liver tissues did not differ with physiological state, but tended to be lowest during lactation. Quantity of DIO2 mRNA in mammary gland increased during lactation (P 100-fold). Quantity of TR beta 1 mRNA in mammary gland increased with onset of lactation, whereas TR alpha 1 and TR alpha 2 transcripts did not vary with physiological state. Conversely, quantity of RXR alpha mRNA decreased during late gestation to low levels during early lactation. Data suggest that increased expression of mammary TR beta 1 and DIO2, and decreased RXR alpha, provide a mechanism to increase thyroid hormone activity within the mammary gland during lactation