Role of the inhibin/activin system and luteinizing hormone in adrenocortical tumorigenesis.
Adrenal masses are one of the most common endocrine tumors diagnosed. Although most adrenal tumors are inactive adenomas, a considerable proportion is associated with hormonal hyperfunction and/or malignancy. The adrenocortical carcinoma (ACC) is a rare but highly malignant tumor. Most ACCs in adults are diagnosed in an advanced tumor stage limiting therapeutic options. Accordingly, despite some progress in diagnostic and therapeutic approaches, the overall survival rate of patients with ACC remains poor. However, the prerequisite for the development of new diagnostic tools and therapeutic options in the management of patients with ACC is the elucidation of the molecular pathogenesis of adrenal tumorigenesis. Although our understanding of adrenal tumor biology has increased substantially over the last decades, the regulation of many molecular pathways involved in adrenocortical growth and differentiation awaits further elucidation. Luteinizing hormone (LH) and activin have only recently emerged as hormones likely to play opposite roles in adrenocortical hormone secretion and cellular proliferation. Recent evidence from studies on human surgical tumor sample expression and detailed characterization of murine adrenal tumor models suggests stimulatory effects of LH on adrenocortical growth and function. On the contrary, activin, which plays a critical role as a paracrine and autocrine factor regulating cellular growth and differentiation, has been demonstrated to induce apoptosis and suppress proliferation in the human and murine adrenal cortex. In this review, we will summarize molecular and functional aspects of adrenal tumorigenesis and highlight some prospects for future clinical applications.
Beuschlein
F
F
Division of Endocrinology and Metabolism, Department of Internal Medicine II, Klinikum der Albert-Ludwigs-Universität, Hugstetter Strasse 55, 79106 Freiburg, Germany. beuschlein@medizin.ukl.uni-freiburg.de
Looyenga
B D
BD
Reincke
M
M
Hammer
G D
GD
D028341:Activins / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000818:Animals; D002277:Carcinoma / Q000209:etiology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007265:Inhibins / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism*; D009385:Neoplastic Processes; D015398:Signal Transduction / Q000502:physiology
D028341:Activins; D007265:Inhibins; D007986:Luteinizing Hormone