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Fetal rat adrenals have been grown in tissue culture. Some specialized properties of the adrenal cortical cells have been studied as an index of their degree of differentiation. Cells transformed morphologically by ACTH differ from controls in their ability to respond rapidly to a single dose of ACTH, as indicated by the yield of isocaproic acid from [26-14C]cholesterol. A correlation was also found between the structure and the steroidogenic activity of the cortical cell mitochondria. Chloramphenicol (0.3 μmole) was found to inhibit the ACTH-induced morphological differentiation of the mitochondria specifically. This inhibition was correlated with a block in the rise of steroid 11β-hydroxylation (mitochondrial) normally induced by ACTH. The rise in steroid 21-hydroxylation (cytoplasmic) was unaffected. The inhibitory effects of chloramphenicol were reversible if the cells were subsequently treated with ACTH alone after removal of chloramphenicol. The present results are consistent with the hypothesis tha...

Antagonists of pituitary trophic hormones may act either by inhibiting the synthesis and release of the hormone, by interfering with the interaction of the trophic hormone with its target tissue, or by inhibiting the intracellular response of the target cell. Taking the adrenocorticotrophin (ACTH) – adrenal cortical cell system some inhibitors of the “trophic” and “acute steroidogenic” responses of the cortical cells to ACTH are described. Finally the problems associated with using inhibitors of specific intracellular functions in the whole animal are considered.

Tissue cultures grown from explants of human fetal adrenals have been maintained for up to 18 days. The morphological and biochemical state of the cortical cells growing from the explants was monitored by phase contrast microscopy and by measuring the extent of conversion of 4-14C-progesterone and 26-14C-cholesterol to labeled products. The cortical cells retained the ability to synthesize steroids throughout the culture periods. In addition, the cells were capable of responding to adrenocor-ticotrophin (ACTH). Cultures exposed to ACTH for 3 or more days showed a marked increase in steroidogenic activity relative to control cultures. ACTH induced concomitant morphological changes in the cells, and characteristic changes in the endoplasmic reticulum and mitochondria were observed in the ACTH-stimulated cells. The results of these experiments suggest that ACTH increases the steroidogenic capacity of fetal adrenal cortical cells in tissue culture and that this increase is associated with proliferation and or...