scholarly journals Mechanism for the development of ovarian cysts in patients with congenital lipoid adrenal hyperplasia

2000 ◽  
pp. 274-279 ◽  
Author(s):  
M Shima ◽  
A Tanae ◽  
K Miki ◽  
N Katsumata ◽  
S Matsumoto ◽  
...  
Keyword(s):  
Body Temperature ◽  
Basal Body ◽  
Regulatory Protein ◽  
Ovarian Cysts ◽  
Adrenal Hyperplasia ◽  
Basal Body Temperature ◽  
Congenital Lipoid Adrenal Hyperplasia ◽  
Steroidogenic Acute Regulatory ◽  
Lh Releasing Hormone ◽  
Star Gene

OBJECTIVE: Although ovarian cysts commonly occur in patients with congenital lipoid adrenal hyperplasia (CLAH), the mechanism of development remains to be determined. To clarify the pathogenesis of the ovarian cysts, endocrinological examinations were performed in patients with CLAH. METHODS: The subjects were three Japanese CLAH patients. Basal body temperature, serum and urinary gonadotropin levels, serum and/or urinary ovarian hormones and mutations of the steroidogenic acute regulatory protein (StAR) gene were examined. RESULTS: The basal body temperature was not biphasic in any patient. Basal LH levels were high in all CLAH patients and markedly responded to LH-releasing hormone in two patients. Urinary gonadotropin analysis revealed repetitive LH surges in the menstrual cycles of the CLAH patients. No increase in the urinary pregnanediol suggested anovulation in all patients, and bilateral ovarian cysts were found in two of the subjects. Examination of the StAR gene revealed a frameshift mutation 840delA at codon 238, a nonsense mutation Q258X at codon 258, a homozygotic mutation at Q258X, and a compound heterozygotic mutation with 251insG and Q258X. CONCLUSIONS: We concluded that the development of ovarian cysts may be derived from continued anovulation in CLAH patients. Elevated LH levels may be explained by increased sensitivity of the anterior pituitary to circulating estrogen.

scholarly journals Congenital Lipoid Adrenal Hyperplasia Caused by a Novel Splicing Mutation in the Gene for the Steroidogenic Acute Regulatory Protein

2004 ◽  
Vol 89 (2) ◽  
pp. 946-951 ◽  
Author(s):  
Alexis A. González ◽  
M. Loreto Reyes ◽  
Cristian A. Carvajal ◽  
Jaime A. Tobar ◽  
Lorena M. Mosso ◽  
...  
Keyword(s):  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Wild Type ◽  
Adrenal Hyperplasia ◽  
Cos Cells ◽  
Star Protein ◽  
Congenital Lipoid Adrenal Hyperplasia ◽  
Intron 1 ◽  
Steroidogenic Acute Regulatory ◽  
Star Gene

Steroidogenic acute regulatory protein (StAR) plays a crucial role in the transport of cholesterol from the cytoplasm to the inner mitochondrial membrane, facilitating its conversion to pregnenolone by cytochrome P450scc. Its essential role in steroidogenesis was demonstrated after observing that StAR gene mutations gave rise to a potentially lethal disease named congenital lipoid adrenal hyperplasia, in which virtually no steroids are produced. We report here a 2-month-old female patient, karyotype 46XY, who presented with growth failure, convulsions, dehydration, hypoglycemia, hyponatremia, hypotension, and severe hyperpigmentation suggestive of adrenal insufficiency. Serum cortisol, 17OH-progesterone, dehydroepiandrosterone sulfate, testosterone, 17OH-pregnenolone, and aldosterone levels were undetectable in the presence of high ACTH and plasma renin activity levels. Immunohistochemical analysis of testis tissues revealed the absence of StAR protein. Molecular analysis of StAR gene demonstrated a homozygous G to T mutation within the splice donor site of exon 1 (IVS1 + 1G>T). Her parents and one brother were heterozygous for this mutation. In vitro analysis of the mutation was performed in COS cells transfected with minigenes coding regions spanning exon-intron 1 to 3 carrying the mutant and the wild-type sequences. RT-PCR analyses of the mutant gene showed an abnormal mRNA transcript of 2430 bp (normal size 433 bp). Sequence analysis of the mutant mRNA demonstrated the retention of intron 1. Immunolocalization of the StAR minigene product detected the peptide in the mitochondria of COS cells transfected with the wild-type minigene but not in those transfected with the mutant minigene. We conclude that this mutation gives rise to a truncated StAR protein, which lacks an important N-terminal region and the entire lipid transfer domain.

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