title: Ovarian histological findings in an adult patient with the steroidogenic acute regulatory protein (StAR) deficiency reveal the impairment of steroidogenesis by lipoid deposition.
abstract: BACKGROUND
  The steroidogenic acute regulatory protein (StAR) is essential for the production of steroid hormones. The mutations in the StAR gene typically cause congenital lipoid adrenal hyperplasia (lipoid CAH), characterized by severe adrenal insufficiency in both sexes and complete female external genitalia in genetic males. Affected 46, XX females feminize at puberty and menstruate but have progressive hypergonadotropic hypogonadism. It has been hypothesized that the cholesterol accumulation in the steroidogenic cells destroys the residual steroidogenic capacity and progressive ovarian failure occurs (two-hit model). Additionally, ovulation and luteinization in the patients is supposed to be impaired. However, those hypotheses have not been confirmed histologically.
  
  
  OBJECTIVE
  We examined whether pathological findings of the ovary in a patient of lipoid CAH corresponded with two-hit model, and whether ovulation and luteinization occurred or not in the patient.
  
  
  METHODS
  The ovary in an adult 46, XX female with a homozygous nonsense mutation (Q258X) in the StAR gene was examined. When the patient was age 22 yr, the ovary was resected because of enlargement with polycysts and subsequent torsion.
  
  
  RESULTS
  The affected ovary demonstrated remarkable lipoid deposition and changes of the mitochondrial ultrastructure. Immunohistochemical examination showed decrease of steroidogenic enzymes such as P450 cholesterol side-chain cleavage (P450scc). Additionally, we detected corpus albicans in the affected ovary.
  
  
  CONCLUSIONS
  This is the first detailed report on ovarian histology in an adult 46, XX female with a null type mutation of the StAR gene (Q258X), which indicates the evidence of the impairment of ovarian StAR-independent steroidogenesis by lipoid deposition.
authors: Department of Endocrinology and Metabolism, Tokyo Metropolitan Kiyose Children's Hospital, Kiyose, Tokyo, Japan.
authors: Uiko
authors: U
authors: Kaku
authors: Kaori
authors: K
authors: Kameyama
authors: Masako
authors: M
authors: Izawa
authors: Makoto
authors: M
authors: Yamada
authors: Junko
authors: J
authors: Miyamoto
authors: Takashi
authors: T
authors: Suzuki
authors: Hironobu
authors: H
authors: Sasano
authors: Yukihiro
authors: Y
authors: Hasegawa
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008064:Lipidoses / Q000150:complications / Q000235:genetics*; D010053:Ovary / Q000473:pathology*; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics*; D013256:Steroids / Q000096:biosynthesis*; D055815:Young Adult; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein