Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 5930-5935 |
| Number of pages | 6 |
| Journal | Journal of Clinical Endocrinology and Metabolism |
| Volume | 89 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2004 Dec |
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ASJC Scopus subject areas
- Biochemistry
- Endocrinology, Diabetes and Metabolism
Cite this
Testicular dysgenesis without adrenal insufficiency in a 46,XY patient with a heterozygous inactive mutation of steroidogenic factor-1. / Hasegawa, Tomonobu; Fukami, Maki; Sato, Naoko; Katsumata, Noriyuki; Sasaki, Goro; Fukutani, Keiko; Morohashi, Ken Ichirou; Ogata, Tsutomu.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 89, No. 12, 12.2004, p. 5930-5935.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Testicular dysgenesis without adrenal insufficiency in a 46,XY patient with a heterozygous inactive mutation of steroidogenic factor-1
AU - Hasegawa, Tomonobu
AU - Fukami, Maki
AU - Sato, Naoko
AU - Katsumata, Noriyuki
AU - Sasaki, Goro
AU - Fukutani, Keiko
AU - Morohashi, Ken Ichirou
AU - Ogata, Tsutomu
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2004-0935
DO - 10.1210/jc.2004-0935
M3 - Article
VL - 89
SP - 5930
EP - 5935
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 12
ER -