Adenylate cyclase activity in membrane fractions of adrenal tissue of human anencephalic fetuses

There is greater basal and ACTH-stimulated adenylate cyclase activity in membrane fractions prepared from the neocortex of human fetal adrenal (HFA) tissue than in similar preparations from thefetal zone. In this study, the specific activity of adenylate cyclase was determined in membrane preparations of adrenal tissue obtained from anencephalic fetuses (n= 5) varying in gestational age from 17-43 weeks. Thebasal adenylate cyclase activity in membrane fractions of adrenals of anencephalics was 2.9 ± 2.1 (mean ± SEM) pmol mgprotein“1 min-1, 3-5% of the average specific activity in membrane preparations of fetal zone or neocortex of normal fetuses. ACTH (10-10-10-4 M) in the incubation mixture stimulated adenylate cyclase activity 2- to 5-fold in whole HFA membrane fractions. In contrast, ACTH, when added to adrenal membrane preparations of the anencephalics, did not stimulate adenylate cyclase activity. Furthermore, sodium fluoride or forskolin stimulated adenylate cyclase activiy markedly in HFA membrane reparations of normal fetuses, but did not affect enzyme activity in adrenal membrane preparations of the anencephalics. In conclusion, the basal activity of adenylate cyclase in adrenal membrane preparations of anencephalics was low and unresponsiveto brief exposure to ACTH, sodium fluoride, or forskolin. These findings as well as those of our previous investigations suggest that the expression of HFA adenylate cyclase may be regulated in part by ACTH. (J Clin Endocrinol Metab 63: 51, 1986) THE human fetal adrenal (HFA) gland, which at term is as large as the adult adrenal gland, secretes large quantities of steroids, principally dehydroepiandrosterone sulfate (DS) (1-7). DS and 16-hydroxydehydroepiandrosteronesulfate, formed infetal liver, serve as the major’ substrates for the large quantities of 17/3- estradiol and estriol secreted by the placenta. In contrast, in pregnancies with an anencephalic fetus, the maternal plasma level of estrogens are low (8). This is due principally to a reduced rate of steroid hormone(mainly DS) secretion by the adrenals of the anencephalic fetus (9,10). In comparison with the normal HFA gland, the adrenals of anencephalic fetuses are markedly reduced in size because of atrophy and involution of the fetal zone, which comprises 85% of the normal fetal adrenal. Although some(11, 12) suggested that the adrenals of anencephalic fetuses are normal until 20 weeks gestation, we and others found that the adrenal glands of anencephalic fetuses are reduced in size as early as 15 weeks gestation (13, 14). It is generally assumed that involution of the adrenals of the anencephalic fetus is Received November 4,1985. Address all correspondence and requests for reprints to: Bruce R. Carr, M.D., Department of Obstetrics and Gynecology, University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, Texas 75235. *This work was supported by USPHS Grants HD-11149 and HD- 17814. due to low circulating levels of ACTH (15,16). Previously, we evaluated the activity of adenylate.