Ovarian histological findings in an adult patient with the steroidogenic acute regulatory protein (StAR) deficiency reveal the impairment of steroidogenesis by lipoid deposition

Uiko Kaku, Kaori Kameyama, Masako Izawa, Makoto Yamada, Junko Miyamoto, Takashi Suzuki, Hironobu Sasano, Yukihiro Hasegawa

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Context: 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. Subject: 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. Result: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)1043-1049
Number of pages7
JournalEndocrine Journal
Volume55
Issue number6
DOIs
Publication statusPublished - 2008

Fingerprint

Protein Deficiency
Ovary
Regulator Genes
Luteinization
Ovulation
Cholesterol
Female Genitalia
Adrenal Insufficiency
Mutation
Hypogonadism
Nonsense Codon
Puberty
Histology
Steroids
steroidogenic acute regulatory protein
Hormones
Enzymes

Keywords

  • Corpus albicans
  • Ovulation
  • StAR
  • Two-hit model

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Ovarian histological findings in an adult patient with the steroidogenic acute regulatory protein (StAR) deficiency reveal the impairment of steroidogenesis by lipoid deposition. / Kaku, Uiko; Kameyama, Kaori; Izawa, Masako; Yamada, Makoto; Miyamoto, Junko; Suzuki, Takashi; Sasano, Hironobu; Hasegawa, Yukihiro.

In: Endocrine Journal, Vol. 55, No. 6, 2008, p. 1043-1049.

Research output: Contribution to journalArticle

Kaku, Uiko ; Kameyama, Kaori ; Izawa, Masako ; Yamada, Makoto ; Miyamoto, Junko ; Suzuki, Takashi ; Sasano, Hironobu ; Hasegawa, Yukihiro. / Ovarian histological findings in an adult patient with the steroidogenic acute regulatory protein (StAR) deficiency reveal the impairment of steroidogenesis by lipoid deposition. In: Endocrine Journal. 2008 ; Vol. 55, No. 6. pp. 1043-1049.
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AB - Context: 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. Subject: 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. Result: 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. Conclusion: 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.

KW - Corpus albicans

KW - Ovulation

KW - StAR

KW - Two-hit model

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