Effects of adrenocorticotropic hormone on low density lipoprotein receptors of human fetal adrenal tissue

In the present investigation, the mechanism (s) whereby ACTH stimulates low density lipoprotein (LDL) metabolism in human fetal adrenal was evaluated. Plasma membrane fractions were prepared from fetal adrenal tissue fragments incubated in lipoprotein-poor serum with or without ACTH, and the binding of [¹²⁵I]iodo-LDL to such membrane fractions was examined. The mean specific binding capacity for [¹²⁵I]iodo-LDL by membrane fractions prepared from four separate fresh human fetal adrenal glands was 1370 ± 168 ng mg^-1 protein (mean ± SE), and the concentration of [¹²⁵I]iodo-LDL producing half-maximal binding was 20.8 + 1.2 ng ml^-1. Thus, the presence of high affinity, low capacity binding sites for LDL in human fetal adrenal tissue was confirmed. When human fetal adrenal tissue was maintained in organ culture for 2 days in medium containing lipoprotein-poor serum in the absence of ACTH, and plasma membrane fractions were subsequently prepared, the binding capacity for LDL in such membrane fractions was the same as or slightly greater than that in membrane fractions prepared from fresh tissue. When ACTH was present in the culture medium, the binding capacity for LDL was doubled compared to that in membrane fractions prepared from tissues incubated in the absence of ACTH. The rate of [¹²⁵I]iodo-LDL degradation by human fetal adrenal tissue maintained in medium containing ACTH was also twice that of tissue maintained in the absence of ACTH. These results demonstrate that ACTH causes an increase in the number of LDL-binding sites in human fetal adrenal tissue in vitro. This is one mechanism whereby ACTH stimulates LDL metabolism in this tissue.