Sex Steroid Influence on Hepatic Gluconeogenesis and Glycogen Formation1

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Abstract
Hepatic gluconeogenesis and glycogen formation were studied in female rats following 21 days of parenterally administered sex steroids to assess the effects of these hormones on liver carbohydrate metabolism and their role in the development of insulin antagonism during pregnancy. Estradiol, progesterone or the two hormones in combination were administered in sesame oil, and control rats received oil alone. Daily dosages of estradiol and progesterone did not exceed 5 μg or 5 mg, respectively. 128 Animals were subdivided into 2–hr and 24–hr fasted groups. Percentage conversion of intravenous alanine— U–14C or pyruvate–3–14C into glucose–14C was followed over a 30 min interval. Suppression of this conversion was most consistently produced with the combined regimen in association with increased percentages of precursor radioactivity appearing in hepatic glycogen. Plasma insulin concentrations were significantly increased in all sex steroidtreated animals relative to control values as was the liver glycogen content when progesterone was administered separately or with estradiol. These results suggest that estradiol and progesterone, especially in combination, suppress hepatic gluconeogenesis while promoting liver glycogen deposition. These insulin-like effects can be related to induced hyperinsulinemia, suggesting that liver does not recognize these sex steroids as insulin antagonists. The hormones appear to have no important role in the generation of diabetogenic stress with respect to hepatic carbohydrate metabolism during pregnancy in the rat. (Endocrinology92: 762, 197)

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