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Cortisol secretion is usually under the control of ACTH. However, cortisol secretion occurs in response to gastric inhibitory polypeptide(GIP) in rare cases of food-dependent Cushing's syndrome. We have investigated whether chronic ACTH stimulation or activation of the ACTH signalling pathway might induce GIPR expression. Reverse transcriptase PCR(RT PCR) revealed GIPR expression in all hyperplastic adrenals studied: 2 ACTH-independent(1 food dependent, 1 Carney complex) and 5 ACTH-dependent Cushing's disease, while no GIPR could be detected in 2 normal adrenals or 20 adrenal adenomas. Primary culture revealed a significant cAMP response to ACTH in all adrenals available for study(EC50 8.1 × 10− 10 M in normals, 4.7 × 10− 10 M in Cushing's disease, 4.4 × 10− 10 M in food-dependent Cushing's syndrome). However, cultures taken from all 4 ACTH-dependent and the 1 food-dependent hyperplastic adrenals studied, were also responsive to GIP(EC50 for cAMP 1.3 × 10− 9 M in Cushing's disease, 4.1 × 10− 10 M in food-dependent disease). Moreover, both hyperplastic adrenals available to study from patients with Cushing's disease, as well as that available from the patient with food-dependent Cushing's syndrome, also demonstrated a cortisol response to GIP. A marked cortisol response to ACTH was observed in all cases studied: 4 fold increase over basal in the case of food-dependent Cushing's syndrome, 6.6- and 6.1-fold increases in the two cases with Cushing's disease. However, a significant response was also observed to GIP in all cases: 5.7-fold increase in the case of food-dependent Cushing's syndrome, 3-fold increase in both cases of Cushing's disease(p < 0.01). Fasting cortisol levels were low in the case of food-dependent Cushing's syndrome, rising postprandially as predicted. However, there were no clinical features suggestive of food-dependency in any of the other cases studied, suggesting that the presence of functional GIPR alone is not sufficient to cause food-dependent Cushing's syndrome. These data are consistent with the hypothesis that chronic ACTH stimulation or constitutive activation of the ACTH signalling pathway may be associated with aberrant GIPR expression, and suggest one mechanism for the pathogenesis of this condition. [ABSTRACT FROM AUTHOR]

We studied the expression of inhibin alpha-subunit in normal and hyperplastic adrenal glands, as well as in various adrenocortical tumors. The protein expression of inhibin alpha was performed by immunohistochemistry. Virilizing adenomas showed strong immunoreactivity against monoclonal inhibin alpha-subunit antibody, whereas other adenomas were only weakly positive or completely negative. In the adrenal cortex no inhibin alpha immunoreactivity was detected in the zona glomerulosa. Zona fasciculata showed weak staining for inhibin alpha, however, strong immunostaining was detected in zona reticularis both in normal and hyperplastic adrenal glands. Adrenal medulla was negative for inhibin alpha. In conclusion, we show high expression of inhibin alpha subunit in zona reticularis of normal and hyperplastic adrenal glands as well as strong expression in virilizing adenomas.