Effects of Parathyroid Hormone on Skeletal Muscle Protein and Amino Acid Metabolism in the Rat

Abstract

A B S T R A C T Because prominent skeletal muscle dysfunction and muscle wasting are seen in both chronic uremia and in primary hyperparathyroidism, and because markedly elevated parathyroid hormone levels occur in both disorders, potential effects of parathyroid hormone on skeletal muscle protein, amino acid, and cyclic nucleotide metabolism were studied in vitro using isolated intact rat epitrochlearis skeletal muscle preparations. Intact bovine parathyroid hormone and the synthetic 1-34 fragment of this hormone stimulated the release of alanine and glutamine from muscle of control but not from chronically uremic animals. This stimulation was dependent upon the concentration of parathyroid hormone added: At 105 ng/ml parathyroid hormone increased alanine release 84% and glutamine release 75%. Intracellular levels of alanine and glutamine were not altered by parathyroid hormone. Increasing concentrations of the 1-34 polypeptide decreased [3HJleucine incorporation into protein of muscles from both control and uremic animals. Using muscles from animals given a pulse-chase label of [guanido-14C]arginine in vivo, parathyroid hormone increased the rate of loss of 14C label from acid-precipitable protein during incubation and correspondingly increased the rate of appearance of this label in the incubation media. Parathyroid hormone increased muscle cAMP levels by 140% and cGMP levels by 185%, but had no effect on skeletal muscle cyclic nucleotide phosphodiesterase activities as assayed in vitro. Adenylyl cyclase activity in membrane preparations from control but not uremic rats was stimulated by parathyroid hormone in a concentration-dependent fashion. However, no stimulation of guanylyl cyclase activity was noted by parathyroid hormone, although stimulation by sodium azide was present. Incubation of muscles with added parathyroid hormone produced a diminished responsiveness towards epinephrine or

Nutritional status of hemodialysis patients with secondary hyperparathyroidism

“…Experimental work on muscle tissue suggests that PTH induces an increase in protein catabolism (18), although this finding has not been confirmed by other investigators (19). Conversely, the effects of secondary hyperparathyroidism on the nutritional status of chronic hemodialysis patients have not been studied.…”

“…In fact, it has been observed that patients with primary hyperparathyroidism may show evidence of weight loss, weakness and muscle atrophy and negative nitrogen balance (15)(16)(17). It is not clear, however, to what extent these findings may be caused by either a direct deleterious effect of PTH on protein metabolism (18) or an indirect effect causing fatigue, anorexia, neuropsychiatric disturbances, myopathy or bone disease (15,16).…”

Resting energy expenditure and its determinants in hemodialysis patients

“…In addition, the hormone may enhance muscle proteolysis and increase the release of alanine and glutamine in vitro (Garber, 1983). If we consider that protein catabolism by circulating PTH may contribute to elevate REE in these patients, then an association of PTH with muscle parameter would be expected.…”

Estado nutricional e ingestão alimentar de pacientes em diálise peritoneal contínua com e sem hiperparatireoidismo secundário

“…13,14 Portanto, os níveis persistentemente altos de PTH podem contribuir diretamente para a desnutrição, já que promovem alteração no metabolismo proteico e energético, conduzindo à perda de peso, fraqueza e atrofia muscular. 13 O PTH é também conhecido por induzir a produção de interleucinas no fígado de ratos e aumentar os níveis circulantes dessas citocinas in vivo.…”

“…[8][9][10] Alterações metabólicas e nutricionais decorrentes da doença e da própria terapia dialítica, como perda de proteínas, aminoácidos e vitaminas hidrossolúveis, supressão do apetite em virtude da absorção contínua de glicose do dialisato, desconforto abdominal, peritonites, diálise pouco eficiente, sobrecarga hídrica, inflamação, acidose metabólica e o HPT2 estão entre as causas da DEP na DPC. 11,12 Alguns estudos experimentais em animais têm demonstrado os efeitos deletérios do PTH no metabolismo proteico; 13,14 porém, pouco tem sido estudado acerca dos efeitos do HPT2 no estado nutricional de pacientes em diálise.…”