Laboratory Investigation

Kidney International (1983) 23, 699–704; doi:10.1038/ki.1983.81

Suppression of parathyroid hormone secretion by aluminum

Jeremiah Morrissey, Marcos Rothstein, Gilbert Mayor and Eduardo Slatopolsky

The Renal Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, and the Department of Medicine, Michigan State University, East Lansing, Michigan

Correspondence: Dr J Morrissey, Renal Division, Department of Medicine, Washington University School of Medicine, P.O. Box 8126. 660 S. Euclid, St. Louis, Missouri 63110, USA

Received 25 April 1982; Revised 7 September 1982.

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Abstract

Suppression of parathyroid hormone secretion by aluminum. The effect of aluminum on parathyroid hormone secretion was examined using collagenase-dispersed bovine parathyroid cells. An increase in the medium aluminum concentration over the range of 0.5 to 2.0 mM, in low calcium medium, progressively inhibited the secretion of radioimmunoassayable hormone. At 2.0 mM aluminum hormone secretion was inhibited by 68% while high medium calcium, without aluminum, maximally inhibited parathyroid hormone secretion only 39%. Individually, 2.0 mM aluminum or 2.0 mM calcium inhibited isoproterenol-stimulated hormone secretion by 43%. Either metal suppressed basal and isoproterenol-stimulated cyclic AMP levels of the parathyroid cells. That the inhibitory effect of aluminum on parathyroid hormone secretion was not due to an irreversible toxic effect was demonstrated by a restoration of normal secretion when cells were returned to 0.5 mM calcium medium without aluminum. The incorporation of [3H]leucine into total cell protein, parathyroid secretory protein, proparathyroid hormone, or parathyroid hormone was not affected by aluminum. The secretion of radiolabeled protein was, however, inhibited by aluminum. These results suggest that aluminum does not affect protein biosynthesis of the parathyroid cell or the conversion of proparathyroid hormone to parathyroid hormone. Aluminum appears to directly affect the secretion of protein from dispersed parathyroid cells.

Suppression de la sécrétion d'hormone parathyroïdienne par l'aluminium. L'effet de l'aluminium sur la sécrétion d'hormone parathyroïdienne a été examiné en utilisant des cellules parathyroïdiennes bovines dispersées par la collagénase. Une élévation de la concentration d'aluminium dans le milieu entre 0,5 et 2 mM, dans un milieu pauvre en calcium, a inhibé progressivement la sécrétion d'hormone parathyroïdienne dosable radioimmunologiquement. A 2,0 mM d'aluminium, la sécrétion hormonale était inhibée de 68%, tandis qu'en milieu riche en calcium, sans aluminium, le maximum d'inhibition de la sécrétion d'hormone parathyroïdienne était de 39% seulement. Individuellement, 2,0 mM d'aluminium ou 2,0 mM de calcium inhibaient la sécrétion hormonale stimulée par l'isoprotérénol de 43%. Les deux métaux supprimaient les concentrations basales et stimulées par l'isoprotérénol d'AMP cyclique dans les cellules parathyroïdiennes. Que l'effet inhibiteur de l'aluminium sur la sécrétion d'hormone parathyroïdienne n'ait pas été dû à un effet toxique irréversible a été démontré par la restauration d'une sécrétion normale lorsque les cellules étaient remises dans un milieu à 0,5 mM de calcium sans aluminium. L'incorporation de [3H]leucine dans les protéines cellulaires totales, la protéine sécrétoire parathyroïdienne, l'hormone proparathyroïdienne ou l'hormone parathyroïdienne n'était pas affectée par l'aluminium. La sécrétion des protéines radio-marquées était, cependant, inhibée par l'aluminium. Ces résultats suggèrent que l'aluminium ne modifie pas la biosynthèse protéique de la cellule parathyroïdienne ni la conversion de l'hormone proparathyroïdienne en hormone parathyroïdienne. L'aluminium semble modifier directement la sécrétion de protéines par les cellules parathyroïdiennes dispersées.

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