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Nur-Related Factor 1 and Nerve Growth Factor-Induced Clone B in Human Adrenal Cortex and Its Disorders

Departments of Pathology (L.L., T.S., Y.Y., Y.M., T.M., H.S.), Pediatric Surgery (L.L., Y.H.), and Second Department of Internal Medicine (O.M.), Tohoku University School of Medicine, 980-8575 Sendai, Japan; and Division of Reproductive Endocrinology (M.H.B., W.E.R.), University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032

Address all correspondence and requests for reprints to: Dr. Takashi Suzuki, Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. E-mail: t-suzuki{at}patholo2.med.tohoku.ac.jp.

Nerve growth factor-induced clone B (NGFI-B; NR4A1) and Nur-related factor 1 (Nurr1; NR4A2) are members of NGFI-B family of orphan receptors. We recently demonstrated induction of CYP11B2 (aldosterone synthase) by Nurr1 and NGFI-B, suggesting possible important roles of these transcriptional factors in the regulation of adrenocortical steroidogenesis. Therefore, we immunolocalized Nurr1 and NGFI-B in various human adrenal specimens to study their biological significance. In nonpathological adrenal glands (n = 25), Nurr1 and NGFI-B immunoreactivities were detected at high levels in the fetal definitive zone or postnatal zona glomerulosa. NGFI-B immunoreactivity was increased according to development in the zona fasciculata, reaching a level similar to that in the zona glomerulosa in adult adrenal cortex. In adrenocortical neoplasms (n = 44), Nurr1 immunoreactivity was higher in aldosteronoma than in Cushing’s adenoma or adrenocortical carcinoma. NGFI-B immunoreactivity was also higher in aldosteronoma than in adrenocortical carcinoma, but was not significantly different among the types of adenoma. Both Nurr1 and NGFI-B mRNA expressions were correlated with their immunoreactivities in adrenocortical neoplasms (n = 23), and mRNA expression of Nurr1 was significantly (P < 0.0001) associated with that of CYP11B2. These results suggest that the expression of Nurr1 and NGFI-B plays an important role in human adrenal cortex and its neoplasms, including possible regulation of steroidogenesis.

This work was supported in part by NIH Grant DK-43140 (to W.E.R.).

Abbreviations: GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; 3ßHSD2, 3ß-hydroxysteroid dehydrogenase type 2; NBRE, nerve growth factor-induced clone B-responsive element; NGFI-B, nerve growth factor-induced clone B; Nurr1, Nur-related factor 1.

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