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Low Density Lipoprotein Binding and de Novo Synthesis of Cholesterol in the Neocortex and Fetal Zones of the Human Fetal Adrenal Gland^*

BRUCE R. CARR, MASAO OHASHI and EVAN R. SIMPSON

Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Departments of Obstetrics and Gynecology and Biochemistry, The University of Texas Southwestern Medical School, Dallas, Texas 75235

Address all correspondence and requests for reprints to: Bruce R. Carr, M.D., Department of Obstetrics and Gynecology, The University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, Texas 75235.

Abstract

The binding of low density lipoprotein (LDL) and the de novo synthesis of cholesterol in separated zones of human fetal adrenal (HFA) tissues were investigated. The number of LDL-binding sites was 2-fold greater in membrane fractions prepared from fresh fetal zone tissue than in those from neocortex tissue. The binding capacity for LDL in fetal zone and neocortex membrane preparations of HFA tissues maintained in culture in the presence of ACTH was 2-fold greater than that in membrane fractions of control tissues. The rates of de novo synthesis of cholesterol also were determined in separated zones of HFA tissue by measuring the specific activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in microsomal fractions prepared from HFA tissues and by determining the rate of incorporation of tritium from [³H]water into cholesterol in HFA tissue fragments. The rate of de novo synthesis of cholesterol in fresh fetal zone tissue was twice that in neocortex tissue as estimated by these methods. When separated zones of HFA tissue were maintained in culture in the presence or absence of ACTH, the rates of de novo synthesis, as determined by the rate of incorporation of tritium from [³H]water into cholesterol, were stimulated to a similar extent by ACTH in both fetal zone and neocortex tissues. However, the specific activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase was increased to a greater extent by ACTH pretreatment in neocortex tissues than in fetal zone tissues. In summary, fetal zone tissues of the HFA gland have a larger number of LDL-binding sites and higher rates of de novo synthesis of cholesterol than do neocortex tissues, and ACTH stimulates LDL binding and de novo synthesis of cholesterol in both zones of the HFA gland.

Footnotes

^* This work was supported in part by USPHS Grants HD-13234 and HD-11149.

Supported in part by a grant-in-aid from the Chilton Foundation

Received August 31, 1981.