Inhibition by parathyroid hormone of glycogen synthesis in the perfused rat liver

Parathyroid hormone can exert effects on metabolic processes; thus it may stimulate renal gluconeogenesis [l-3] or adipose tissue lipolysis [4-61. The renal content of cyclic adenosine 3’5’ monophosphate (cyclic AMP) is increased in response to parathyroid hormone, [ 1,7] . Hormones which act in the above fashion on kidney or fat, might be expected, by analogy with e.g. adrenalin and glucagon, to stimulate hepatic glycogen breakdown. Therefore this possibility was tested in the perfused rat liver. Rather than following glucose output, glycogen metabolism was tested directly, to exclude effects on gluconeogenesis; thus net glycogen synthesis was measured, as previously described [9,10]. This process exhibits greater sensitivity to another ‘catabolic’ hormone, viz. vasopressin, than does glycogen breakdown in livers from fed rats [lo] , which was another reason for selecting glycogen synthesis for study. The results presented here demonstrate that parathyroid hormone can inhibit hepatic net glycogen synthesis. During the progress of these experiments, reports appeared of stimulation by parathyroid hormone of glucose output in hepatocytes [ 1 l] and of cyclic AMP formation by the liver [ 11,121. The present work complements these studies, in documenting the hormone concentration-dependence of the action on hepatic glycogen metabolism, in the perfused liver, i.e. in a preparation where hormone responses may be reasonably presumed to correspond closely to events in vivo . Male Sprague-Dawley rats (200 g) were starved for 48 h from 10.00 h. Net glycogen synthesis was measured by a sequential-biopsy procedure in livers perfused with 50 ml saline containing albumin, red cells, glucose and gluconeogenic precursors, as described previously [9,10]. Parathyroid hormone (Lot 74/286) was very kindly provided by Dr J. A. Parsons (National Institute of Medical Research, Mill Hill, London, NW7, UK), and Dr J. R. L. O’Riordan (Middlesex Hospital, London W.l., UK). This material contained, per ampoule, 170 gg highly purified hormone, and 259 mg mannitol. For use, it was dissolved in about 1 ml 1% (w/v) bovine serum albumin (‘Crystalline’, Sigma Ltd) which had been heated at 56°C (pH 7.0) for 2 h. When the entire ampoule of hormone was not used during a day’s perfusions, the solution (pH 4.0) was rapidly frozen (using liquid nitrogen) in small aliquots, being used subsequently after only one thaw.