Source:http://linkedlifedata.com/resource/pubmed/id/10522996
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
1999-11-4
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| pubmed:abstractText |
We have studied a 20-yr-old male patient with adrenal hypoplasia congenita and hypogonadotropic hypogonadism (HH) due to a C to A transversion at nucleotide 825 in the DAX-1 gene, resulting in a stop codon at position 197. The same mutation was detected in his affected first cousin (adrenal hypoplasia congenita and HH) and in a heterozygous state in their carrier mothers. The patient had had acute adrenal insufficiency at the age of 2 yr and 6 months, bilateral cryptorchidism corrected surgically at the age of 12 yr, and failure of spontaneous puberty. Plasma testostereone (T) was undetectable (<0.30 nmol/L), gonadotropin levels were low (LH, <0.4 IU/L; FSH, 1.5 IU/L) and not stimulated after i.v. injection of 100 microg GnRH. The endogenous LH secretory pattern was apulsatile, whereas free alpha-subunit (FAS) levels depicted erratic pulses, suggesting an incomplete deficiency of hypothalamic GnRH secretion. During i.v. pulsatile GnRH administration (10 microg/pulse every 90 min for 40 h), each GnRH pulse induced a LH response of low amplitude (0.54 +/- 0.05 UI/L), whereas mean LH (0.45 +/- 0.01 IU/L) and FAS (63 +/- 8 mU/L) levels remained low. Amplitude of LH peaks (0.83 +/- 0.09 IU/L), mean LH (0.53 +/- 0.02 IU/L), and FAS (161 +/- 18 mU/L) levels increased (P < 0.01), whereas the T concentration remained low (0.75 nmol/L) when the pulsatile GnRH regimen was raised to 20 microg/pulse for a 40-h period, suggesting a partial pituitary resistance to GnRH. Thereafter, plasma T levels remained in prepubertal value after three daily im injections of 5000 IU hCG (3.6 nmol/L) and after 1-yr treatment with weekly i.m. injections of 1500 IU hCG (1.2 nmol/L), implying Leydig cell resistance to hCG. The patient had a growth spurt, bone maturation, progression of genital and pubic hair stages, and normalization of plasma T level (15.8 nmol/L) after a 12-month treatment with twice weekly injections of hCG and human menopausal gonadotropin (75 IU International Reference Preparation 2) preparations, suggesting that, in presence of FSH, a Sertoli cell-secreted factor stimulated Leydig cell production of T. In conclusion, we report a novel mutation in the DAX-1 gene in patients with AHC and HH. Our results suggest that the hypogonadism is due to a combined hypothalamic-pituitary-gonadal defect and imply that the DAX-1 gene may play a critical role in human testicular function.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chorionic Gonadotropin,
http://linkedlifedata.com/resource/pubmed/chemical/DAX-1 Orphan Nuclear Receptor,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoprotein Hormones, alpha Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Gonadotropin-Releasing Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Luteinizing Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Menotropins,
http://linkedlifedata.com/resource/pubmed/chemical/NR0B1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0021-972X
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
84
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3563-9
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:10522996-Base Sequence,
pubmed-meshheading:10522996-Child, Preschool,
pubmed-meshheading:10522996-Chorionic Gonadotropin,
pubmed-meshheading:10522996-DAX-1 Orphan Nuclear Receptor,
pubmed-meshheading:10522996-DNA-Binding Proteins,
pubmed-meshheading:10522996-Drug Therapy, Combination,
pubmed-meshheading:10522996-Genitalia, Male,
pubmed-meshheading:10522996-Glycoprotein Hormones, alpha Subunit,
pubmed-meshheading:10522996-Gonadotropin-Releasing Hormone,
pubmed-meshheading:10522996-Humans,
pubmed-meshheading:10522996-Hypogonadism,
pubmed-meshheading:10522996-Hypothalamo-Hypophyseal System,
pubmed-meshheading:10522996-Luteinizing Hormone,
pubmed-meshheading:10522996-Male,
pubmed-meshheading:10522996-Menotropins,
pubmed-meshheading:10522996-Mutation,
pubmed-meshheading:10522996-Pedigree,
pubmed-meshheading:10522996-Receptors, Retinoic Acid,
pubmed-meshheading:10522996-Repressor Proteins,
pubmed-meshheading:10522996-Transcription Factors
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| pubmed:year |
1999
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| pubmed:articleTitle |
Combined hypothalamic-pituitary-gonadal defect in a hypogonadic man with a novel mutation in the DAX-1 gene.
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| pubmed:affiliation |
Service d'Endocrinologie et Maladies Métaboliques, CHU Rangueil, Toulouse, France. caron.p@chu-toulouse.fr
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| pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, Non-U.S. Gov't
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