Stimulation of purine synthesis in vitro in the calf thyroid by thyroid-stimulating hormone.

There have been many observations describing morphological and biochemical alterations in the thyroid after administration of thyroid-stimulating hormone. The hormone has been shown to increase oxygen consumption (l-3), incorporation of P32 into phospholipids (4), iodide uptake (5), the formation of iodotyrosines (6, 7), and glucose oxidation (8, 9) by thyroid tissue in vitro. There have recently been efforts to relate the many effects of the hormone to some fundamental action on a single metabolic site. It has been proposed that the primary action of TSHI in the thyroid is to stimulate glucose oxidation via the hexose monophosphate pathway (9). This effect is specific for thyroid tissue and for TSH and can be detected as early as 5 minutes after the addition of physiological amounts of the TSH to the medium (9, 10). The finding that the concentration of triphosphopyridine nucleotide is increased in thyroid slices incubated with TSH (11) suggests that the increased glucose oxidation is secondary to the changed triphosphopyridine nucleotide level. In thyroid homogenates, the concentration of triphosphopyridine nucleotide is a limiting factor in glucose oxidation (12). Evidence has been presented that TSH may increase TPN levels by a conversion of DPN to TPN (II), but other mechanisms have also been post.ulated (7). Schussler and Ingbar (7) have recently shown that TPN stimulates the formation of monoiodotyrosine in homogenates of sheep thyroid gland. They have proposed that the energy for this reaction is derived from glucose via TPN-linked dehydrogenations. The stimulating action of TSH on this process can therefore be explained on the basis of its known action on glucose oxidation. This paper concerns the action of TSH on purine synthesis in the calf thyroid. Incorporation of CWformate into acid-soluble and ribonucleic acid purines is specifically stimulated by TSH at physiological dose levels. Evidence will be presented relating the action of TSH on purine synthesis to its known effect in stimulating the hexose monophosphate pathway.