title: Steroidogenic enzyme profile in an androgen-secreting adrenocortical oncocytoma associated with hirsustism.
abstract: Hirsutism induced by hyperandrogenism can be associated with polycystic ovary syndrome, 21-hydroxylase (OH) deficiency or androgen-secreting tumors, including ovarian and adrenal tumors. Adrenal androgen-secreting tumors are frequently malignant. Adrenal oncocytomas represent rare causes of hyperandrogenism. The aim of the study was to investigate steroidogenic enzyme expression and steroid secretion in an androgen-secreting adrenal oncocytoma in a young woman presenting with hirsutism. Hyperandrogenism was diagnosed on the basis of elevated plasma Δ4-androstenedione and testosterone levels. Pelvic ultrasound was normal, CT scanning revealed a right adrenal mass. Androgens were assessed in adrenal and ovarian vein samples and proved a right adrenal origin. Adrenalectomy normalized androgen levels and the adrenal tumor was diagnosed as an oncocytoma. Real time-PCR, immunohistochemistry and cell culture studies were performed on tumor explants to investigate the steroid secretion profile. Among enzymes required for cortisol synthesis, 17α-OH and 3β-hydroxysteroid dehydrogenase 2 (3β-HSD2) were highly expressed whereas 21-OH and 11β-OH were weakly produced at the mRNA and/or protein levels. Enzymes involved in testosterone production, 17β-HSD5 and 17β-HSD3, were also detected. ACTH receptor was present in the tissue. Cortisol, Δ4-androstenedione and testosterone secretions by cultured cells were increased by ACTH. These results provide the first demonstration, to our knowledge, of abnormal expression profile of steroidogenic enzymes in an adrenocortical oncocytoma. Our results also indicate that Δ4-androstenedione hypersecretion resulted from high 17α-OH and 3β-HSD2 expression in combination with low expression of 21-OH and 11β-OH. Testosterone production was ascribed to occurrence of 17β-HSD5 and 17β-HSD3. Finally, our results indicate that androgen secretion was stimulated by ACTH.
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France.
authors.forename: Milène
authors.initials: M
authors.lastname: Tetsi Nomigni
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Ouzounian
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Benoit
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Vadrot
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Tissier
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Renouf
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-e
authors.forename: Hervé
authors.initials: H
authors.lastname: Lefebvre
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Christin-Maitre
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont-Saint-Aignan, France University of Rouen Mont-Saint-Aignan, France Department of Endocrinology Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France Departments of Endocrinology Diabetes and Metabolic Diseases Pathology Hôpital Sud Francilien, Corbeil-Essonnes, France Department of Pathology Assistance Publique des Hôpitaux de Paris, Hôpital Pitié Salpétrière, Pierre-et-Marie Curie University, Paris, France Department of Endocrinology Diabetes and Metabolic Diseases, Rouen University Hospital, 76000 Rouen, France INSERM U933, Paris, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Louiset
keywords: androgen-producing oncocytoma; cortisol; hirsutism; testosterone; Δ4-androstenedione