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Ovine Placental Lactogen Inhibits Glucagon-Induced Glycogenolysis in Fetal Rat Hepatocytes^*

Departments of Pediatrics and Physiology, Duke University Medical Center, Durham North Carolina 27710

Address requests for reprints to: Michael Freemark, M.D., Duke Medical Center, Box 3080, Durham, North Carolina 27710.

Abstract

The effect of ovine placental lactogen (oPL) on glucagon-stimulated glycogenolysis was studied in cultured hepatocytes from 20-day-old fetal rats. Pretreatment of hepatocytes with oPL (0.5-5 Mg/ml) significantly attenuated the inhibitory effect of glucagon on glycogen synthesis. Hepatocytes exposed to glucagon alone at 1, 5, and 20 nM incorporated 32.0, 43.2, and 62.1% less [¹⁴C]glucose into glycogen than control hepatocytes. However, hepatocytes pretreated for 1 h with oPL (1 Mg/ml) and then exposed to the same concentration of glucagon incorporated only 5.8, 9.2, and 22.1% less [¹⁴C]glucose than control cells (P < 0.01 vs. glucagon alone). In cells preincubated for 24 h in medium containing [¹⁴c]glucose, glucagon reduced cellular [¹⁴c]glycogen and total glycogen content by 47.1 and 51.0% while oPL increased total cellular glycogen content by 105.8% and attenuated the glycogen-degradative effect of glucagon. While oPL alone had no effect on basal phosphorylase a (Pa) activity, oPL (1-10 µg/ml) caused a 15.3-91.6% inhibition of glucagon-stimulated Pa activity (P < 0.01). The maximal inhibition by oPL of glucagon-stimulated Pa activity occurred within 2 min of exposure to oPL, and the effect was not blocked by cycloheximide. oPL also caused a 49.4-95.0% inhibition of (Bu)₂cAMP-stimulated Pa activity (P < 0.01), suggesting that the inhibitory effect of oPL on glucagon action is exerted, at least in part, at a site distal to the intracellular accumulation of cAMP. Insulin (1 µM) reduced basal Pa activity, abolished the stimulation of Pa activity by glucagon, and markedly attenuated the stimulation of Pa by (Bu)₂-cAMP. These studies demonstrate that oPL acutely inhibits glycogen degradation in fetal rat hepatocytes and suggest that oPL promotes glycogen storage in fetal liver both by antagonizing the glycogenolytic effects of glucagon and by stimulating fetal hepatic glycogenesis. (Endocrinology 116: 1275- 1280,1985)

Footnotes

^* This work was supported by NIH Grants HD-07447 and HD-06301.

Received August 13, 1984.