| Factors that affect the clearance of progesterone by the hepatocyte were examined. In study one, the objective was to determine if increased hepatic portal acetate or propionate could alter hepatic metabolism of progesterone. Serum concentrations of progesterone after an oral gavage of either acetate or propionate began to diverge as early as 0.5 h and were different (P < 0.05) at 3-h and 4-h for ewe lambs gavaged with acetate or propionate, respectively. Increasing portal vein propionate reduced progesterone clearance. In study two, the objective was to determine the effect of a single oral gavage of either acetate or propionate on peripheral concentrations of insulin and glucagon in the ewe. Serum concentrations of insulin, after an oral gavage of either acetate or propionate, were different (P < 0.05) at 0.5 h and 1 h for ewe lambs orally-gavaged with acetate and propionate, respectively. Further, serum concentrations of glucagon, after an oral gavage of either acetate or propionate, were different (P < 0.05) at 0.5 h, 1 h and 2 h for ewe lambs orally-gavaged with acetate and propionate, respectively. The last study determined progesterone clearance in response to challenge with different concentrations of insulin, glucagon or a combination of insulin and glucagon in a hepatic cell line. In response to a challenge with insulin, there was a dose dependant decrease in the disappearance of progesterone. There was a reduction (P < 0.05) in the rate of decay with the addition of 0.1 nM insulin. Further, there was a greater reduction (P < 0.05) in the rate of decay in response to 1.0 and 10 nM insulin than control and 0.1 nM insulin. There was no observable change in the disappearance of progesterone with either physiological (0.01 nM) or pharmacological (0.1 and 1.0 nM) treatment with glucagon. Pharmocological concentrations of glucagon (1.0 nM) negated the effects of either 0.1 or 1.0 nM insulin on the clearance of progesterone. However, with physiological concentrations of glucagon (0.01 nM) and 1.0 nM insulin, glucagon was not able to negate the reduction in progesterone disappearance caused by insulin. |
