It has been shown that lipoprotein and, specifically, low density lipoprotein (LDL) are the principal source of cholesterol utilized for steroidogenesis in normal human fetal adrenal (HFA) tissue. ACTH causes an increase in the number of LDL receptors and in the rate of degradation of LDL as well as an increase in de novo synthesis of cholesteral in normal HFA tissue. In a previous investigation, we found that cortisol synthesis in ACTH-treated adrenal tissue obtained from an anencephalic newborn was not stimulated further by the addition of lipoprotein-cholesterol. In the present investigation, we sought to ascertain whether adrenal tissue from anencephalic newborns could bind LDl and if ACTH could increase the rate of metabolism of LDL by this tissue. The rate of cholesterol synthesis in adrenal tissue from anencephalic newborns was determined by measuring 1) the rate of incorporation of [14C]acetate into cholesterol, 2) the specific activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, and 3) the rate of incorporation of tritium from [3H]water into cholesterol in fresh tissues and in adrenal tissues maintained in culture in the presence or absence of ACTH. These results were compared to those obtained utilizing adrenal tissues from normal abortuses. The specific binding of [125I]iodoLDL to membrane preparations of adrenal tissue from anencephalic newborns was one-sixth that in adrenals of normal abortuses. The degradation of [125I]iodoLDL in adrenal tissues of anencephalic newborns was not stimulated by ACTH, whereas in normal HFA tissue, degradation of LDL was increased 2-fold by ACTH. The rate of cholesterol synthesis in fresh adrenal tissue of anencephalic newborns, as determined by the specific activity of HMG CoA reductase and the incorporation of tritium from [3H]water into cholesterol, was one-tenth and one-third, respectively, of the rates obtained in normal HFA tissue. When adrenal tissues from anencephalic newborns was maintained for 3 days in the presence of ACTH, the rate in incorporation of [14C]acetate into cholesterol was stimulated, findings to those using normal HFA tissue. The specific activity of HMG CoA reductase and the rate of incorporation of tritium from [3H]water into cholesterol also were stimulated by ACTH but were, respectively, only one-fifth and one-third that in normal HFA tissue. These findings suggest that the content of LDL receptors in adrenals of anencephalic newborns is low due to chronic low levels of ACTH in fetal plasma. The adrenals of anencephalic newborns synthesized cholesterol de novo and ACTH caused an increase in cholesterol synthesis, findings that suggest that this is the principal mechanism whereby adrenal tissue of the anencephalic fetus obtains cholesterol precursor for steroidogenesis.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Clinical Endocrinology and Metabolism|
|State||Published - 1981|
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism