Male hypogonadism caused by homozygous deletion of exon 10 of the luteinizing hormone (LH) receptor: Differential action of human chorionic gonadotropin and LH

We report the unique case of a patient with Leydig cell hypoplasia (LCH) ty pe II caused by a genomic deletion resulting in the complete absence of exo n 10 of the LH receptor (LHR). The patient presented at the age of 18 yr wi th retarded pubertal development, small testicles, and delayed bone maturat ion. LH was highly elevated, with very low serum testosterone levels. Genet ic analysis revealed a homozygous deletion of approximately 5 kbp encompass ing exon 10 of the LHR gene. Screening of family members demonstrated heter ozygosity for the deletion, indicating autosomal recessive inheritance. At the time of examination, the patient displayed nearly normal male phenotype , but lacked pubertal development and was hypogonadal. Obviously, fetal mal e development sustained by hCG was normal, whereas LH action, important for pubertal development, was impaired. A hCG stimulation test induced testost erone biosynthesis and secretion within the normal range. Subsequently, hCG treatment was continued, resulting in an increase in testicular volume and the appearance of spermatozoa in the ejaculate after 16 weeks of treatment (5.3 million/mL). Despite highly elevated endogenous LH serum levels, the response to hCG indicates a possible dual mechanism of hormone binding and signal transduction for hCG and LH on a LHR that lacks exon 10. Furthermore , this patient represents the clinical counterpart of the normal male marmo set monkey (Callithrix jacchus), in which the expressed LHR lacks exon 10 i n toto. This case provides important clinical insights about the possible r ole of exon 10 of the LHR in discriminating between LH and hCG actions.