Abstract
Relative lipolytic activity of human parathyroid hormone-(1-34) (hPTH-(1-34], hPTH-(3-34), desamino-Ser1-hPTH-(1-34), and rat PTH-(1-34) was compared in human subcutaneous adipose tissues in vitro. Human PTH-(1-34), rat PTH-(1-34), and desamino-Ser1-hPTH-(1-34) stimulated in vitro lipolysis significantly above basal level at the concentration of 10(-6) M. Average increments of lipolytic rate were 2.39, 1.82, and 0.87 mumol/g per 2 hr, respectively, being significantly different among the three groups. On the other hand, hPTH-(3-34)-induced lipolytic rate was 0.83 +/- 0.18 mumol/g per 2 hr, not significantly different from the basal level (0.71 +/- 0.20 mumol/g per 2 hr). The effect of hPTH-(3-34) on glycerol release stimulated by hPTH-(1-34), isoproterenol, or forskolin was subsequently investigated. Human PTH-(3-34) produced a dose-dependent inhibition of hPTH-(1-34)-stimulated lipolysis. In contrast, isoproterenol- and forskolin-induced lipolytic rates were not influenced by hPTH-(3-34). The effect of propranolol on hPTH-(1-34)- or isoproterenol-induced lipolysis was also studied. Propranolol dose-dependently inhibited isoproterenol-induced lipolysis but had no effect on lipolysis stimulated by hPTH-(1-34). These results suggest that the amino acids at positions 1 (serine) and 2 (valine) of PTH are critical for the stimulation of lipolysis in human adipose tissue. Human PTH-(1-34) causes lipolysis after binding to receptors distinct from beta-adrenergic receptors of fat cells and possibly hPTH-(3-34) inhibits hPTH-(1-34)-stimulated lipolysis by competing at the level of PTH receptor.
Highlights
Relative lipolytic activity of human parathyroid hormone-(1-34) (hPTH-(1-34)), hPTH-(3-34), desamino-SerlhPTH-(1-34), and rat Parathyroid hormone (PTH)-(1-34)was compared in human subcutaneous adipose tissues in vitro
The addition of hPTH-(1-34) significantly stimulated lipolysis in human subcutaneous adipose tissues at a concentration of M (P < 0.05) and the maximum lipolytic rate was attained at a concentration of lo-' to M (Fig. 1)
The maximum lipolytic rate stimulated by forskolin was observed at a concentration of Taniguchi et al Effects of PTH fragments on lipolysis in human adipose tissue 491 r
Summary
Relative lipolytic activity of human parathyroid hormone-(1-34) (hPTH-(1-34)), hPTH-(3-34), desamino-SerlhPTH-(1-34), and rat PTH-(1-34)was compared in human subcutaneous adipose tissues in vitro. Human PTH-(1-34), rat PTH-(1-34), and desamino-Ser'-hPTH-(1-34)stimulated in vitro lipolysis significantly above basal level at the concentration of M. HPTH-(3-34)-induced lipolytic rate was 0.83 0.18 pmollg per 2 hr, not significantly different from the basal level (0.71 kO. pmollg per 2 hr). Human PTH-(3-34) produced a dose-dependent inhibition of hPTH-(l-34)-stimulated lipolysis. Isoproterenol- and forskolin-induced lipolytic rates were not influenced by hPTH-(3-34). The effect of propranolol on hF'TH-(1-34)- or isoproterenol-induced lipolysis was studied. Propranolol dose-dependently inhibited isoproterenolinduced lipolysis but had no effect on lipolysis stimulated by hPTH-(1-34).IThese results suggest that the amino acids at positions 1 (serine) and 2 (valine) of PTH are critical for the stimulation of lipolysis in human adipose tissue.
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