Abstract | OBJECTIVE: The study describes for the first time, a homozygous mutation in the WSXWS-like motif of the human GH receptor (GHR) in a patient with Laron syndrome and describe laboratory data during treatment with GnRHa to suppress puberty and dihydrotestosterone (DHT). PATIENTS: A 16-year-old boy at Tanner puberty stage 2 with Laron syndrome was born SGA to consanguineous parents, presented severe growth retardation, obesity and micropenis. METHODS AND MEASUREMENTS: GHR coding region was sequenced. GH, GHBP, IGF-I and IGFBP-3 were determined before, during and after GnRHa and DHT treatment. RESULTS: A homozygous mutation in exon 7, replacing serine by isoleucine in codon 226 was identified. S226 is the last serine belonging to the WSXWS-like motif in GHR. No specific effect of S226I mutation in heterozygous state was observed. Laboratory data at the prepubertal age showed markedly high GH, low GHBP, IGF-I and IGFBP-3 levels. Re-evaluation at pubertal age showed normal basal serum IGFBP-3 levels and low but near normal IGF-I levels. We also noticed a sustained decrease in GH, IGF-I and IGFBP-3 levels after blocking puberty, which was not affected by short- and long-term DHT treatment. Pubertal hormonal profile was re-established after the GnRHa therapy was discontinued to allow the reactivation of the gonadal axis. CONCLUSION: The homozygous mutation S226I in WSXWS-like motif of GHR causes GH insensitivity. The decrease in IGF-I and IGFBP-3 levels after GnRHa therapy, which was not reversed with DHT administration, suggests that sex steroids have, through oestradiol, a GH-independent action on IGF-I and IGFBP-3 levels. A direct effect of GnRHa on GH secretion cannot be excluded.
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Authors | Alexander A L Jorge, Silvia C A L Souza, Ivo J P Arnhold, Berenice B Mendonca |
Journal | Clinical endocrinology
(Clin Endocrinol (Oxf))
Vol. 60
Issue 1
Pg. 36-40
(Jan 2004)
ISSN: 0300-0664 [Print] England |
PMID | 14678285
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- (N-acetyl-tyr1,D-arg2)fragment 1-29 amide
- Insulin-Like Growth Factor Binding Protein 3
- Peptide Fragments
- Receptors, Somatotropin
- Dihydrotestosterone
- Insulin-Like Growth Factor I
- Growth Hormone
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Topics |
- Amino Acid Motifs
- Amino Acid Sequence
- Base Sequence
- Child
- Consensus Sequence
- Dihydrotestosterone
- Growth Disorders
(drug therapy, genetics)
- Growth Hormone
(blood)
- Homozygote
- Humans
- Insulin-Like Growth Factor Binding Protein 3
(blood)
- Insulin-Like Growth Factor I
(analysis)
- Male
- Molecular Sequence Data
- Mutation
- Pedigree
- Peptide Fragments
(therapeutic use)
- Puberty
(blood)
- Receptors, Somatotropin
(genetics)
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