Testicular dysgenesis without adrenal insufficiency in a 46,XY patient with a heterozygous inactive mutation of steroidogenic factor-1

Tomonobu Hasegawa, Maki Fukami, Naoko Sato, Noriyuki Katsumata, Goro Sasaki, Keiko Fukutani, Ken Ichirou Morohashi, Tsutomu Ogata

研究成果: ジャーナルへの寄稿学術誌査読

88 被引用数 (Scopus)

抄録

Steroidogenic factor-1 (SF-1) regulates multiple genes involved in the adrenal and gonadal development and in the biosynthesis of a variety of hormones, including adrenal and gonadal steroids, anti-Mullerian hormone (AMH), and gonadotropins. We identified a novel SF-1 mutation in a 27-yr-old Japanese patient with a 46,XY karyotype. Sequence analysis was performed for all the seven exons of SF-1, revealing a heterozygous single base pair deletion at exon 2 (18delC) that is predicted to cause a frameshift at the sixth codon and resultant termination at the 74th codon. Functional studies showed that the mutation produced no demonstrable protein and had no transcription activity or dominant negative effect. Clinical features included small dysgenetic testes with vasa deferentia and epididymides, absent uterus, blind-ending vagina, clitoromegaly, and psychosexual disturbance. Endocrine studies showed normal adrenal function (cortisol response to ACTH stimulation, 13.4→25.3 μg/dl) and primary hypogonadism (testosterone response to hCG stimulation, 0.57→0.76 ng/ml; gonadotropin responses to GnRH stimulation: LH, 10→59 mIU/ml; FSH, 36→69 mlU/ml), and urinary steroid hormone profile analysis indicated grossly normal steroidogenic enzyme activities. The results suggest that SF-1 haploinsufficiency can selectively impair testicular development and permit the biosynthesis of AMH and testosterone in dysgenetic testes and the production of gonadotropins in pituitary gonadotropes.

本文言語英語
ページ(範囲)5930-5935
ページ数6
ジャーナルJournal of Clinical Endocrinology and Metabolism
89
12
DOI
出版ステータス出版済み - 12月 2004
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 内分泌学
  • 臨床生化学
  • 生化学、医学

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