Δ4-5α-HYDROGENASE DER LEBER UND NEBENNIERENRINDEN-AKTIVITÄT UNTER EINFLUSS VON SCHILDDRÜSENHORMON

ABSTRACT In experiments with male rats the in vivo effects of thyroxine (T4) and triiodothyronine (T3) on the following parameters were investigated: the microsomal Δ4-5α-hydrogenase activity of the liver, the adrenal weight and the in vitro corticosterone production rate. Either thyroid hormone leads to the known increase in the cortisone reduction rate. However, there are two different mechanisms underlying this effect. While the effect of T4 after two or three days of treatment is due to an increase in the production of reduced NADP by the liver cell with no change in the Δ4-5α-hydrogenase activity (McGuire & Tomkins 1959), treatment for only two days with T3 causes an increase in microsomal activity. The activity of the microsomal preparation without additions is zero for both the control and the T3 treated animals. If increasing quantities of NADP are added together with glucose-6-phosphate and glucose-6-phosphate dehydrogenase, then for each addition of NADP up to the maximum value the activity of the Δ4-5α-hydrogenase of the treated animals is always considerably higher by the same percentage than that of the controls. With animals possessing low Δ4-5α-hydrogenase activity treatment with T3 leads to a greater percentage increase in the enzyme activity than with animals having higher hydrogenase activities. There exists a very close correlation (r = 0.94) between hydrogenase activity and its percentage increase due to T3 administration. The regression-line indicates that with hydrogenase activities greater than 12 T3 is without effect. This leads to the view that the hepatic action of T3 is to promote steroid hydrogenation up to a fixed turnover rate. Although the increase in the adrenal weight was the same with either thyroid hormone, only T3, not T4, was simultaneously effective in raising corticosterone production rate in vitro. Thus, an increase in the adrenal weight is not in any case the expression of an enhanced hormone secretion rate. The fact that the administration of T4 significantly increases Δ4-5α-hydrogenase activity and adrenal weight without concomitant increase in corticosterone production rate must be regarded as evidence against the assumption that the adrenal effect of T4 is simply the consequence of the primary acceleration of corticosteroid turnover in the liver.