Tetrahydrobiopterin increases in adrenal medulla and cortex: a factor in the regulation of tyrosine hydroxylase.

Tetrahydrobiopterin, the cofactor for tyrosine hydroxylase and other monooxygenases, is present in tissues at apparent concentrations much less than those necessary to saturate the corresponding enzymes. Reserpine treatment or insulin-induced hypoglycemia in rats produces a statistically significant increase in the tetrahydrobiopterin content of both the adrenal medulla and the cortex. Adrenal denervation and hypophysectomy selectively block the increases in cofactor level in medulla and cortex, respectively, while cycloheximide prevents the increase in both tissues. Reserpine did not increase cofactor levels in liver, kidney, or corpus striatum but decreased that of the pineal gland. These results suggest that tetrahydrobiopterin is under neural control in the medulla and hormonal control in the cortex and that increases in cofactor may result from induction of enzyme(s) in the biosynthetic pathway. These results demonstrate regulation of tissue tetrahydrobiopterin and are consistent with the suggestion that cofactor levels participate in the regulation of tyrosine hydroxylase in the adrenal medulla and may have a function, as yet undetermined, in the adrenal cortex.