Endocrine Abstracts

Testicular adrenal rest tumors (TART) are frequently detected in male patients with 21-hydroxylase (21-OH) deficiency. Increase in plasma ACTH levels, due to cortisol deficit, is responsible for TART growth. Indeed, glucocorticoid substitution reduces both plasma ACTH and TART development in the majority of patients. Nevertheless, some patients with TART are resistant to the glucocorticoid treatment, suggesting the existence of other factors stimulating TART growth. The aim of the study was to characterize the phenotype of TART cells in the testicular tissue of a treatment-resistant 38-year-old patient. It also aimed to investigate the expression of the serotonin (5-HT) signaling pathway in TART, similar to that described in adrenal hyperplasias of patients with 21-OH mutations (Le Mestre et al. JCEM 2019; 104:4967-80). Immunostainings showed the presence of ACTH receptor (MC2R), 3β-hydroxysteroid dehydrogenase (3β-HSD2), a steroidogenic enzyme involved in the synthesis of glucocorticoids and androgens, and 11β-hydroxylase, the key enzyme for cortisol production, in the majority of TART cells. In addition, some tumor cells were immunopositive for 17β-HSD type 5 (17β-HSD5, AKR1C3), the enzyme responsible for testosterone synthesis in adrenal glands, whereas they were immunonegative for 17β-HSD3, the testicular isoenzyme. The study revealed the expression of TPH1, the limitant enzyme in 5-HT synthesis, and 5-HT receptor types 4 and 6 in the tissue. These data confirm the adrenal phenotype of TART cells and demonstrate expression of several actors of the 5-HT signaling pathway in the patient’s TART tissue. This work should be extended to a series of TART tissues. Moreover, in vitro functional studies conducted on TART cell cultures might evaluate a possible role of locally-produced 5-HT on tumor cell proliferation.