A new constitutively activating point mutation in the luteinizing hormone/choriogonadotropin receptor gene in cases of male-limited precocious puberty.
A phase II study in testotoxicosis is currently underway,exploring the combination of a highly selective anti-androgen, bicalutamide, and the potent aromatase inhibitor, anastrozole.
A sporadic case of male-limited precocious puberty has the same constitutively activating point mutation in luteinizing hormone/choriogonadotropin receptor gene as familial cases.
He presented with precocious puberty at 10 months of age and was diagnosed with testotoxicosis due to a de novo heterozygous Asp578Tyr mutation in LHCGR.
Here we study two unrelated boys suffering from a paradoxical combination of testotoxicosis and pseudohypoparathyroidism type Ia (PHP-Ia), a condition marked by resistance to hormones acting through cyclic AMP (parathyroid hormone and thyroid-stimulating hormone) as well as a 50% decrease in erythrocyte Gs activity (the remaining 50% is due to the normal Gs allele).
Here, we described the long-term follow-up of a 24-year-old young man with severe testotoxicosis due to a de novo activating mutation in the third transmembrane helix of the LHCGR (p.Leu457Arg).
Inactivating mutations of the luteinizing hormone receptor (LHR) gene in males induce Leydig cell agenesis or hypoplasia, while activating mutations cause testotoxicosis.
Spontaneous fertility in a young man with severe testotoxicosis and chronic suppression of FSH levels reinforces the key role of high intratesticular testosterone levels in human spermatogenesis.
Together, these analyses suggest that exon 11 of human LHCGR could be more susceptible to mutation than the other 10 exons together and that activation of LHCGR, contingent to the somatic silencing of neighbouring ALF, could be linked to male-limited precocious puberty and pre-eclampsia.
Treatment of familial male-limited precocious puberty (testotoxicosis) with anastrozole and bicalutamide in a boy with a novel mutation in the luteinizing hormone receptor.