The Hydroxylation of Vitamin D on C25 in Thyrotoxicosis The Role of the Activity of Microsomal Liver Enzymes

Abstract

Vitamin D<sub>3</sub> after its entrance in the organism undergoes hydroxylation on C-25 carbon atom by the action of microsomal liver enzymes giving the metabolite 25 hydroxyvitamin D<sub>3</sub> (25OHD<sub>3</sub>). The function of microsomal liver enzymes is influenced in some specified states by hormones or drugs. It has approved that thyroxin is a potent stimulator of these enzymes while allopurinol suppresses their function. The aim of this issue is to examine 25OHD<sub>3</sub> plasma levels in thyrotoxic subjects and in those pretreated with allopurinol on the base of the afford mentioned data. In a first phase 25OHD<sub>3</sub> plasma levels were estimated in thyrotoxic subjects against euthytoid healthy controls. In a second phase lmg vitamin D<sub>3</sub> was injected intravenously (i.v.) in thyrotoxic subjects and in healthy euthyroid controls. 25OHD<sub>3</sub> plasma levels were measured before and in post injection period in six hours intervals for 48 hours. In a third phase a couple of subjects one thyrotoxic and one euthyroid healthy control pretreated both with allopurinol injected lmg of vitamin D<sub>3</sub> i.v. In all studied subjects 25OHD<sub>3</sub> plasma levels were measured before and in post injection period in six hours intervals for 48 hours. The pre and post injection 25OHD<sub>3</sub> plasma levels measured the size of activity of liver enzyme responsible for bioactivation of vitamin D<sub>3</sub>. In the first phase was indicated that 25OHD<sub>3</sub> plasma levels were lower in thyrotoxic subjects comparing with that of euthyroid healthy controls (p < 0.001). In the second phase was found that the bioactivation of vitamin D<sub>3</sub> in thyrotoxic subjects was 2,5 to 8 times faster comparing with euthyroid healthy controls. In the third phase was shown that allopurinol decreases the activity of liver enzymes function as regard the bioactivation of vitamin D<sub>3</sub>. The bioactivation of vitamin D<sub>3</sub> is accelerated in thyrotoxicosis compared with that in euthyroid state. This phenomenon produces low 25OHD<sub>3</sub> plasma levels in thyrotoxic subjects which initially may be normal or slightly increased depended from the vitamin D<sub>3</sub> status in the thyrotoxic subjects. By continuous stimulatory action of increased thyroid hormones on liver enzymes the 25OHD<sub>3</sub> plasma levels earlier or later decline in levels of hypo-or avitaminosis D3. The previously described biological events may explain the decreased intestinal calcium absorption of vitamin D<sub>3</sub> and the osteomalacic component found in a percentage of thyrotoxic bone histology. For the blocking effects of allopurinol on liver enzymes function and possibly of other pharmaceutical products in relation to vitamin D<sub>3</sub> bioactivation, available...

Severe Thyrotoxicosis Does Not Accelerate 1a-Hydroxylation of 25-Hydroxyvitamin D3 in Dogs. Experimental Study

“…Thyrotoxicosis represents a morbid condition that gradually deprives the body of Vitamin D. In thyrotoxicosis, the plasma levels of 1,25-dihydroxyvitamin D (1, 25(OH) 2 D) are depressed. Moreover, hydroxylation of Vitamin D on C25 position for the production of 25-hydroxyvitamin-D (25OHD) is accelerated resulting in low plasma levels of Vitamin D [1][2][3]. The accelerated hydroxylation of Vitamin D on C25 position in cases of thyrotoxicosis is due to the stimulation of liver microsomal enzymes (CYP27A1, CYP2J3, CYP2R1, CYP3A4) by the thyroid hormones.…”