Endocrine-dependent regulation of tetrahydrobiopterin levels and guanosine triphosphate cyclohydrolase activity.

The role of endocrine organs in the regulation of tetrahydrobiopterin (BH4) levels and guanosine triphosphate cyclohydrolase (GTP-CH) activity was studied in the spleen, bone marrow and brain of rats and mice. Following hypophysectomy, BH4 levels and GTP-CH activity were significantly decreased in both spleen and bone marrow. Fourteen days after hypophysectomy GTP-CH activity and BH4 levels were approximately 25% of control levels in both tissues. In contrast, BH4 levels and GTP-CH activity in brain were not significantly different from control values. The decrease in GTP-CH activity and BH4 levels in spleen and marrow could not be reversed by high doses of ACTH or by a pituitary extract. Removal of the thyroid gland resulted in significant decreases in BH4 levels and GTP-CH activity in spleen; marrow and brain levels were not affected. BH4 levels in spleens of thyroidectomized rats returned to control values following treatment with either triiodothyronine or thyroxine. Adrenalectomy and castration had no effect on biopterin metabolism in bone marrow, spleen or brain. Tissue levels of BH4 and GTP-CH were also studied in mutant mouse strains having mutations in either pituitary or thyroid functions in order to examine further the role of these tissues in the regulation of the biosynthesis of this cofactor. The results of this study indicate that factors secreted from the pituitary are important in the regulation of BH4 levels and GTP-CH activity in spleen and bone marrow and that the thyroid gland also plays a role in regulation in the spleen. Levels of BH4 and GTP-CH in the brain, if regulated, appear to be independent of the endocrine tissues studied.