The present investigation was performed in order to study the properties of abnormal membrane function related to
ACTH receptor-
adenylate cyclase system interaction in human
ACTH-unresponsive
adrenocortical cancer. Two tissues of
adrenocortical cancer obtained from a patient with
Cushing's syndrome (CS) and a case presenting no abnormal endocrinological findings (NF) were used for in vitro studies, comparing with three normal adrenal tissues. The addition of
ACTH alone and
ACTH plus 10(-6) M GppNHp did not enhance the
adenylate cyclase (AC) activity in the CS and NF tissues. Relative insensitivity of AC to
GTP, GppNHp, and
cholera toxin was observed for the NF tissue, while the rate of response to GppNHp for the CS tissue which also showed relative insensitivity to
GTP and
cholera toxin was similar to that for the normal tissues.
Forskolin which is reported to directly activate the catalytic unit of the AC complex increased the AC activity of both CS and NF tissues as well as that of the normal tissues. Therefore, the function of the catalytic unit itself may be rather well preserved in these
tumor tissues. These results suggest that the lack of
ACTH receptor at the cell membrane surface might be responsible for
ACTH-unresponsiveness in the CS tissue, although an accelerated degradation of
GTP could contribute to decreased activity of
GTP-binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)