The control of liver regeneration by calcitonin, parathyroid hormone and 1 alpha,25-dihydroxycholecalciferol.
Removal of the thyroid in normocalcemic rats with functional parathyroid transplants was found to reduce the hepatocyte DNA synthetic activity which normally follows partial hepatectomy. This proliferative incapacitation of hepatocytes appeared to be due specifically to a calcitonin deficiency since it was overcome by a single injection of pure synthetic salmon calcitonin shortly after partial hepatectomy. Salmon calcitonin and bovine parathyroid hormone were equally able to reverse the similar proliferative incapacitation of hepatocytes in hypocalcemic rats which had both their parathyroid and thyroid glands removed one day before partial hepatectomy. However, these two hormones (individually or together) could not reverse the proliferative incapacity resulting from a more prolonged (3-day) exposure to the hypocalcemic conditions in thyroparathyroidectomized rats, but the proliferative incapacity could be reversed by simultaneous treatment with the vitamin D3 metabolite, 1 alpha,25-dihydroxycholecalciferol. We suggest that extracellular calcium ions are the actual regulators of this hormonally-controlled hepatocyte proliferative development and that parathyroid hormone and the vitamin D3 metabolite affect proliferation indirectly by determining the extracellular calcium concentration, while calcitonin directly, or indirectly, sensitizes hepatocytes to the action of calcium.
D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008940:Mitotic Index; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D013965:Thyroidectomy
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D002116:Calcitonin; D004247:DNA; D002118:Calcium; D013936:Thymidine