Hormonal regulation of DNA polymerase-β activity in the rat thyroid gland

Abstract

Using hypophysectomized rats, it has been shown that DNA polymerase-beta activity in the adrenal gland and testis is largely influenced by pituitary trophic hormones. Sucrose gradient centrifugation of thyroid extracts revealed three peaks of DNA polymerase-beta activity sedimenting at 3.3S, 7.3S and 12S. Of these, hypophysectomy induced a decrease in the 3.3S DNA polymerase-beta, whereas other molecular forms were affected only slightly. DNA polymerase-alpha and -gamma activities were unaffected by hypophysectomy. These changes in DNA polymerase-beta caused by hypophysectomy were reversed by daily i.p. injection of TSH. Furthermore, stimulation of the thyroid by excess TSH induced by the administration of 1-methyl-2-mercaptoimidazole resulted in an increase of all forms of thyroid DNA polymerase-beta. These results show that the level of DNA polymerase is relatively constant after hypophysectomy but that DNA polymerase-beta in the rat thyroid gland is also modulated by TSH mainly through the change of activity of the polymerase-beta which sediments at 3.3S.

Enhancement of DNA Polymerase β Activity in the Pituitary Gland by Hormonal Feedback

“…The B-enzyme in the bovine pituitary gland displayed a single sedimentation constant (3.3 S) as in adrenal gland and testis, whereas, in the anterior lobe of rat pituitary glands, multiple S-Values of the B-enzyme (3.3 S, 7.3 S and 12 S) were observed and the activity of each fraction increased upon pituitary cell hyperfunction. Similar results were obtained in human and rat thyroid glands (Nagasaka, Yoshida, Nakai, Ohyama, Iwase, Ohtani, Shinoda, Masunaga and Nakagawa 1988b;Nagasaka et al 1988a), namely that the B-enzyme from human thyroid glands sedimented at 3.3 S, whereas that in rat thyroids sedimented in three activity peaks, 3.3, 7.3 and 12 S, all of which had characteristics of the B-enzyme. It is unlikely that exonuclease coexists with the B-enzymes in multiple Svalues (Nagasaka, Yoshida, Ohyama, Masunaga, Kato, Suzuki, Itoh and Kawabe 1990).…”

“…1, the B-enzyme activity in the anterior and posterior lobes of the bovine pituitary gland sedimented at 3.3 S in sucrose gradient centrifugation and its peak level was higher in the anterior than in the posterior lobe, consistent with results in the extract. In order to know the possible correlation between the B-enzyme and the endocrine function of rat pituitary glands as was observed in adrenal (Nagasaka and Yoshida 1982), testes (Nagasaka and Yoshida 1984) and thyroid (Nagasaka et al 1988a), we attempted to elucidate whether or not activity of the B-enzyme is augmented in pituitary thyrotrophic cells stimulated by the negative feedback mechanism in the hypothyroid state induced by i.p. injection of an antithyroid drug (MMI).…”

“…We previously proposed that the activity of the B-enzyme might reflect the functional level of endocrine organs, using rat adrenal and thyroid glands and testes (Nagasaka and Yoshida 1982;Nagasaka et al 1988a;Nagasaka and Yoshida 1984) as well as the human thyroid gland (Nagasaka et al 1988b). The increased B-enzyme activity in the pituitary anterior lobe of MMI-treated rats agrees well with our hypothesis: it may be due to hyperfunction of pituitary thyreotrophic cells (DeFesi, Astier and Surks 1979;Carretero, Sanchez, Torres, Blanco, Riesco and Vazquez 1989).…”

Relationship of eukaryotic DNA replication to committed gene expression: general theory for gene control.

“…Terminal differentiation in which endoreduplication is not thought to be involved may also involve DNA polymerase beta. Reports of lowered or absent polymerase alpha levels and constant or elevated polymerase beta levels in differentiated (but not undifferentiated) thyroid tissue (264,265), nervous tissue (180), erythroleukemia cells (262), regenerating-differentiating rat liver (270), developing rat (270) or chick (243) brain, and differentiating chick lens (243) are consistent with a role of polymerase beta in terminal differentiation, distinct from mitotic replication, which is associated with polymerase alpha (243). A more direct assessment of possible DNA polymerase beta participation in terminal differentiation was recently reported by Zmudzka and Wilson (410).…”

Thyroglobulin may affect telomerase activity in thyroid follicular cells

“…We have reported that thyroglobulin inhibits thyroidal DNA polymerase b [46] and reverse transcriptase [47], both of which, like TA, are RNAdependent DNA polymerases. This suggests that a similar mechanism may be involved in the inhibitory action of thyroglobulin on these enzymes.…”