CHICKEN PARATHYROID-HORMONE GENE-EXPRESSION IN RESPONSE TO GASTRIN, OMEPRAZOLE, ERGOCALCIFEROL, AND RESTRICTED FOOD-INTAKE

Treatment with omeprazole, a long-acting proton pump inhibitor of acid secretion, induces hypergastrinemia. In chickens, omeprazole Induces growth not only of the acid-producing mucosa (probably reflecting the trophic action of gastrin), but also of the parathyroid glands (hypert rophy + hyperplasia), while suppressing bone density and body weight g ain without affecting blood calcium. The first part of the present stu dy was concerned with the effect of omeprazole, ergocalciferol (vitami n D-2), and restricted food intake on the gene expression of parathyro id hormone (PTH) in the parathyroid glands of the chicken. Chickens we re treated with omeprazole (400 mu mol/kg/day, I.M.), food restriction , omeprazole + food restriction, ergocalciferol (250 000 IU/kg/day, S. C.), or ergocalciferol + omeprazole for 5 weeks. The weight gain of th e chickens was monitored, and the weights of the parathyroid glands an d femurs were determined at sacrifice. PTH mRNA in the parathyroid gla nds was analyzed by Northern blot. The sec ond part of the study exami ned the effect of 3 weeks of continuous gastrin infusion (chicken gast rin 20-36, 5 nmol/kg/hour, S.C.) on the expression of PTH mRNA in the parathyroid glands. Omeprazole reduced the body weight and femur densi ty (ash weight per volume) while greatly increasing the weight of the parathyroid glands and the PTH gene expression. Food restriction alone and ergocalciferol alone (at a dose that raised blood Ca2+) were with out effect, but food restriction greatly enhanced the omeprazole-evoke d increase in parathyroid gland weight and PTH gene expression. Gastri n increased the weight of the parathyroid glands and reproduced the ef fect of omeprazole on PTH gene expression. Hence, it seems likely that the effect of omeprazole reflects the ensuing hypergastrinemia.