JOURNAL ARTICLE

Gonadal macrophage infiltration in congenital lipoid adrenal hyperplasia

Tomohiro Ishii, Ryuji Fukuzawa, Takeshi Sato, Koji Muroya, Masanori Adachi, Kenji Ihara, Junko Igaki, Yukihiro Hasegawa, Seiji Sato, Toshikatsu Mitsui, Tomonobu Hasegawa
European Journal of Endocrinology 2016, 175 (2): 127-32
27190208

OBJECTIVE: Congenital lipoid adrenal hyperplasia (lipoid CAH) results in impairment of adrenal and gonadal steroidogenesis caused by STAR mutations. Our previous study revealed upregulation of genes associated with inflammatory or immune response and macrophage infiltration in the adrenal cortex of Star-knockout mice. This study aimed at investigating macrophage infiltration in the gonads from human patients with lipoid CAH.

DESIGN: This study includes seven patients with lipoid CAH who underwent gonadectomy: two XX women (age, 22 and 40 years) and five XY boys (1 year). Two women with ovarian cysts (32 and 40 years) and six boys with autopsy or tumor (1 year) were examined as controls. Immunohistochemical analysis of their gonads was performed to determine steroidogenic cells by NR5A1 or CYP17A1 and macrophages by IBA1 or CD68.

RESULTS: An increased number of macrophages infiltrated into the ovaries of lipoid CAH and consisted of two subpopulations: one scattered within and around a layer of theca cells of maturing follicles and the other massively aggregated in the stroma. Abundant cytoplasmic lipid droplets were observed not only in the theca cells but also in the stromal macrophages. There was no significant difference in the number of macrophages in the testicular interstitium between lipoid CAH (95% confidence interval (95% CI: 19.3-47.7 per 0.2mm(2)) and controls (95% CI: 13.3-25.8 per 0.2mm(2)) (P=0.10).

CONCLUSIONS: These results demonstrate that macrophages infiltrate the ovaries of lipoid CAH, where the theca cells and the stromal macrophages have abundant cytoplasmic lipid droplets.

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