Hepatic lecithin: Retinol acyltransferase activity is induced in vivo by retinoic acid, but not by triiodothyronine, in vitamin A-deficient, hypothyroid rats

The activity of the enzyme lecithin: retinol acyltransferase (LRAT) is extremely low in the liver of vitamin A-deficient rats, but is rapidly induced after administration of retinoic acid IRA). The nuclear receptors for RA are closely related to the receptors for thyroid hormone, and molecular cross-talk between these receptors has been observed in vitro and in cultured cells. Therefore we have examined whether retinoid status and thyroid hormone status interact in the regulation of hepatic LRAT activity in vivo. Vitamin A-deficient male Lewis rats, either euthyroid or made hypothyroid by treatment with propylthiouracil, were treated once or three times with 20 μg of all-trans-RA, 10 μg/100 gm body weight of triiodothyronine (T₃), or both hormones. Hepatic LRAT activity, which was negligible in all retinoid-deficient rats, was induced by RA (P < 0.0001) regardless of the animal's thyroid hormone status. T₃ by itself had no ability to induce hepatic LRAT activity (P = 0.42), nor did co-administration of T₃ with RA increase or decrease the response to RA (P = 0.13). In retinoid-sufficient rats, hypothyroidism did not alter hepatic LRAT activity; however, LRAT activity was reduced by half (P < 0.05) after three treatments with T₃. Therefore we conclude that thyroid hormone status alone does not regulate LRAT, nor does thyroid status affect the ability of RA to induce hepatic LRAT in retinoid-deficient animals. However, in retinoid-sufficiency, repeated treatment with T₃ may reduce the hepatic esterification of retinol by LRAT.