Endogenous cholesterol synthesis is sufficient for ACTH-induced differentiation of rat adrenocortical cells in primary culture |
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Authors: | Päivi Heikkilä Arvi I Kahri Christian Ehnholm Petri T Kovanen |
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Institution: | (1) National Public Health Institute, Helsinki, Finland;(2) Wihuri Research Institute, Helsinki, Finland;(3) Department of Pathology, University of Helsinki, Haartmaninkatu 3, SF-00290 Helsinki, Finland |
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Abstract: | Summary To define the role of endogenously synthesized cholesterol in the differentiation of adrenocortical cells in primary culture,
fetal rat adrenal cells were cultured in the presence of exogenous cholesterol (serum-supplemented medium) or in the absence
of it (serum-free medium or lipoprotein-free medium). Ultrastructurally the cells had features of glomerulosa cells: mitochondria
were oval or rod shaped with lamellar inner membranes. The amount of smooth endoplasmic reticulum was small, and lipid droplets
were few. When the cells were cultured in serum-free medium some intracytoplasmic vacuoles were seen. The undifferentiated
zona glomerulosa-like cells secreted low amounts of corticosterone and 18-OH-deoxycorticosterone (18-OH-DOC) in all three
media (serum-supplemented medium, serum-free medium, and lipoprotein-free medium). Stimulation of the adrenocortical cells
with ACTH induced the ultrastructural features of differentiated zona fasciculata-like cells. Mitochondrial inner membranes
were well developed in lipoprotein-free medium, but not in serum-free medium. The amount of intracellular lipids was increased
in both media devoid of cholesterol. In the ACTH stimulated cultures the presence of exogenous cholesterol resulted in increased
secretions of corticosterone and 18-OH-DOC. In the absence of an exogenous source of cholesterol, the amounts of steroids
secreted were only half of that secreted in the presence of serum-supplemented medium. Endogenously synthesized cholesterol
is sufficient for the morphologic differentiation of fetal rat adrenocortical cells under ACTH stimulation. However, without
exogenously provided cholesterol, the steroid production accounts only for half of the maximal output achieved using serum-supplemented
medium.
This work was supported by Finnish Culture Foundation. |
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Keywords: | rat adrenal cortex tissue culture endogenous cholesterol ultrastructure corticosterone 18-OH-deoxycorticosterone |
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