Growth hormone regulation of serum lipoproteins in the rat: Different growth hormone regulatory principles for apolipoprotein (apo) B and the sexually dimorphic apo E concentrations

Abstract

Growth hormone (GH) regulation of serum lipoproteins and apolipoproteins was studied using hypophysectomized (Hx) male and female Sprague-Dawley rats. Hypophysectomies were performed at 45 or 50 days of age. Hx rats were given replacement therapy with l-thyroxine (10 μg/kg/d) and hydrocortisone (400 μg/kg/d) unless otherwise specified. Bovine GH (bGH) was given either as two daily subcutaneous (SC) injections at 12-hour intervals or as a continuous SC infusion. Serum cholesterol and apolipoprotein (apo) E concentrations decreased after Hx of female rats. In contrast, Hx of male rats resulted in increased serum cholesterol concentrations and had no effect on serum apo E concentrations. There were no effects of Hx on high-density lipoprotein (HDL) apo E levels in male rats in contrast to female rats. bGH given twice daily to Hx male rats had no effect on HDL apo E levels, but a continuous infusion of bGH resulted in a marked increase in HDL apo E concentration, to levels above those of intact male rats. As previously observed in female rats, serum and HDL apo A-I concentrations decreased and serum and low-density lipoprotein (LDL) concentrations of apo B increased after Hx of male rats. Treatment with l-thyroxine and hydrocortisone reduced the serum concentrations of apo B. bGH given alone resulted in even lower concentrations of apo B. Serum concentrations of cholesterol and apo E were unaffected by replacement therapy with l-thyroxine and hydrocortisone. Treatment with bGH alone had similar effects on serum cholesterol, apo E, and apo B concentrations as treatment with l-thyroxine, hydrocortisone, and bGH in combination. The time course and dose-response relationship for the effects of GH were studied in Hx female rats. Serum apo B concentrations increased during the first day after Hx and decreased after 1 day of bGH treatment. The changes in apo E concentration were observed 3 days after Hx and 3 to 7 days after initiation of hormonal treatment, respectively. The apo B concentration decreased dose-dependently and reached the levels of intact females when the highest doses (1 to 2 mg/kg/d) of bGH were given. In contrast, the apo E concentration increased to the levels of intact females when a low dose (0.05 mg/kg/d) of bGH was infused, and did not increase further with higher doses. The changes in serum cholesterol concentration were similar to those of apo E. These results indicate that there are sex differences in the regulation of serum cholesterol and apo E concentrations by the pituitary and that these differences may be dependent on the sexually dimorphic secretion of GH. The pituitary regulation of the nonsexually differentiated apo B concentrations was similar in male and female rats and GH treatment decreased serum apo B concentrations independent of the mode of administration. Furthermore, the different time courses and dose-response relationships suggest different regulatory mechanisms for the regulation of apo E and apo B concentrations by GH in the rat.