Functional and ultrastructural changes during ACTH-induced early differentiation of cortical cells of human fetal adrenals in primary cultures

Abstract

Early events during ACTH-induced differentiation of cortical cells of human fetal adrenals in primary cultures were studied by electron microscopy and steroid analysis. In undifferentiated cortical cells, the basal secretion of steroids was very low. The first sign of ACTH stimulation was a marked increase in pregnenolone sulfate secretion during the first 24 hr, indicating the activation of “pregnenolone synthetase” enzyme. The main shift towards differentiated function occurred during the second and third days of stimulation, shown by increased secretion of ll-deoxycortisol, corticosterone, cortisol, and dehydroepiandrosterone sulfate, while the pregnenolone sulfate concentration decreased. Aldosterone secretion increased only very slightly and slowly during ACTH stimulation. The first change in the morphology of cortical cells was the rounding of the cells during the first 24 hr. Ultrastructurally this was seen by a transformation of plasma membrane into microvillous projections and a loosening of the cell connections. The main functional activation of cortical cells was reflected later as increased smooth endoplasmic reticulum membranes.