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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) type II caused by a genomic deletion resulting in the complete absence of exon 10 of the LH receptor (LHR). The patient presented at the age of 18 yr with retarded pubertal development, small testicles, and delayed bone maturat...

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Published in:The journal of clinical endocrinology and metabolism 2000-06, Vol.85 (6), p.2281-2286
Main Authors: GROMOLL, J, EIHOLZER, U, NIESCHLAG, E, SIMONI, M
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EIHOLZER, U
NIESCHLAG, E
SIMONI, M
description We report the unique case of a patient with Leydig cell hypoplasia (LCH) type II caused by a genomic deletion resulting in the complete absence of exon 10 of the LH receptor (LHR). The patient presented at the age of 18 yr with retarded pubertal development, small testicles, and delayed bone maturation. LH was highly elevated, with very low serum testosterone levels. Genetic analysis revealed a homozygous deletion of approximately 5 kbp encompassing exon 10 of the LHR gene. Screening of family members demonstrated heterozygosity 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 male development sustained by hCG was normal, whereas LH action, important for pubertal development, was impaired. A hCG stimulation test induced testosterone 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 marmoset monkey (Callithrix jacchus), in which the expressed LHR lacks exon 10 in toto. This case provides important clinical insights about the possible role of exon 10 of the LHR in discriminating between LH and hCG actions.
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Obstetrics</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Hypogonadism - blood</topic><topic>Hypogonadism - genetics</topic><topic>Inhibins - blood</topic><topic>Leydig Cells - pathology</topic><topic>Luteinizing Hormone - blood</topic><topic>Male</topic><topic>Male genital diseases</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Non tumoral diseases</topic><topic>Pedigree</topic><topic>Puberty, Delayed - blood</topic><topic>Puberty, Delayed - genetics</topic><topic>Receptors, LH - genetics</topic><topic>Sequence Deletion</topic><topic>Testis - anatomy &amp; histology</topic><topic>Testosterone - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GROMOLL, J</creatorcontrib><creatorcontrib>EIHOLZER, U</creatorcontrib><creatorcontrib>NIESCHLAG, E</creatorcontrib><creatorcontrib>SIMONI, M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GROMOLL, J</au><au>EIHOLZER, U</au><au>NIESCHLAG, E</au><au>SIMONI, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Male hypogonadism caused by homozygous deletion of exon 10 of the luteinizing hormone (LH) receptor : Differential action of human chorionic gonadotropin and LH</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2000-06-01</date><risdate>2000</risdate><volume>85</volume><issue>6</issue><spage>2281</spage><epage>2286</epage><pages>2281-2286</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>We report the unique case of a patient with Leydig cell hypoplasia (LCH) type II caused by a genomic deletion resulting in the complete absence of exon 10 of the LH receptor (LHR). 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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 marmoset monkey (Callithrix jacchus), in which the expressed LHR lacks exon 10 in toto. This case provides important clinical insights about the possible role of exon 10 of the LHR in discriminating between LH and hCG actions.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>10852464</pmid><doi>10.1210/jc.85.6.2281</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Adolescent
Adult
Base Sequence
Biological and medical sciences
Bone Development
Chorionic Gonadotropin - blood
Exons
Female
Follicle Stimulating Hormone - blood
Genetic Carrier Screening
Gynecology. Andrology. Obstetrics
Homozygote
Humans
Hypogonadism - blood
Hypogonadism - genetics
Inhibins - blood
Leydig Cells - pathology
Luteinizing Hormone - blood
Male
Male genital diseases
Medical sciences
Molecular Sequence Data
Non tumoral diseases
Pedigree
Puberty, Delayed - blood
Puberty, Delayed - genetics
Receptors, LH - genetics
Sequence Deletion
Testis - anatomy & histology
Testosterone - blood
title Male hypogonadism caused by homozygous deletion of exon 10 of the luteinizing hormone (LH) receptor : Differential action of human chorionic gonadotropin and LH
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