Structure of the human luteinizing hormone-choriogonadotropin receptor gene: unusual promoter and 5′ non-coding regions

Atger, Michel; Misrahi, Micheline; Sar, Sokhavuth; Flem, Léna Le; Dessen, Philippe; Milgröm, Edwin

doi:10.1016/0303-7207(95)03557-n

Cited by 97 publications

(66 citation statements)

References 45 publications

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“…Exon 1 of LHR gene was amplified with primers GhLHR1 (5 CACTCAGAGGCCGTCCAAG 3) E GhLHR2 (5 GGAG GGAAGGTGGCATAGAG 3) as described by Atger et al [37]. In brief, amplification was performed in a Veriti thermal cycler (Life Technologies) at annealing temperature of 64°C, using 20 pmol of each primer, 0.5 U Taq DNA Polymerase, 2 mM dNTP and 1.5 mM MgCl2 (all reagents from Invitrogen, Paisley, UK).…”

Section: Detection Of Inslq In Lhreceptor Genementioning

confidence: 99%

LH (Trp8Arg/Ile15Thr), LHR (insLQ) and FSHR (Asn680Ser) polymorphisms genotypic prevalence in women with endometriosis and infertility

Schmitz

Souza

Genro

et al. 2015

J Assist Reprod Genet

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Purpose To verify if polymorphisms of LH (Trp8Arg/Ile15Thr), LH receptor (insLQ), and FSH receptor (Asn680Ser) are associated with endometriosis and infertility. Methods This is a prospective case-control study. Sixtyseven patients with endometriosis and infertility (study group) and 65 healthy fertile patients (control group) were enrolled in the study between July 2010 and July 2013. All patients had their endometriosis diagnosis made or excluded by laparoscopic surgery; study group was submitted to the surgery for infertility investigation and control group for tubal ligation. Day-3 serum hormones were collected from all patients. Analysis of nucleotide mutations for LH polymorphisms (Trp8Arg and Ile15Thr), LHR polymorphism (insLQ), and FSHR polymorphism (Asn680Ser) were performed by PCR.Results Day-3 FSH, estradiol and LH serum levels were not different between the groups, while CA-125 was higher in patients with endometriosis and infertility. All polymorphisms studied were in Hardy-Weinberg equilibrium. The prevalence of insLQ was significantly higher in patients with endometriosis and infertility (P=0.005). Allele occurrence in control group was 0.10 versus 0.25 in infertile endometriosis group (P=0.001). There was no difference regarding Trp8Arg/Ile15Thr (P>0.05) and Asn680Ser (P>0.05) prevalence between groups. Conclusion This is the first time that prevalence of insLQ was shown to be higher in patients with endometriosis and infertility than in healthy fertile patients. There was no difference in LH and FSHR polymorphisms' prevalence between groups.

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Section: Detection Of Inslq In Lhreceptor Genementioning

confidence: 99%

LH (Trp8Arg/Ile15Thr), LHR (insLQ) and FSHR (Asn680Ser) polymorphisms genotypic prevalence in women with endometriosis and infertility

Schmitz

Souza

Genro

et al. 2015

J Assist Reprod Genet

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“…Genomic DNA was purified using the Nucleon Kit (Herolab, Braunschweig, Germany). Exons 1-11 of the LHR gene were amplified using the primers and cycling conditions described by Atger et al (11). Each PCR sample (25 ml) contained 10 nmol/l Tris -HCl (pH 8.3), 50 nmol/l KCl, 0.01% gelatin, 2 nmol/l MgCl 2 , 0.2 mmol/l deoxy-NTPs, 2 U Taq polymerase (Promega Corp., Heidelberg, Germany), 20 pmol/l primer, and 200 ng DNA.…”

Section: Dna Isolation and Pcr Analysismentioning

confidence: 99%

Homozygous mutation within the conserved Ala-Phe-Asn-Glu-Thr motif of exon 7 of the LH receptor causes male pseudohermaphroditism

Gromoll¹,

Schulz

Borta³

et al. 2002

European Journal of Endocrinology

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Background: Human chorionic gonadotropin/luteinizing hormone (hCG/LH) function in the male is mediated by the LH receptor (LHR) and is crucial for the normal development of internal and external genitalia. We report a 46, XY patient who presented at the age of 16 with a female phenotype and delayed puberty. Gonads were located bilaterally in the inguinal canal, removed surgically and showed hypoplastic Leydig cells. Immunostaining for the LHR revealed that some Leydig cell progenitors were positive, while others were negative, reflecting different developmental stages of Leydig cell maturation. Methods and Results: Molecular analysis of the LHR was performed on DNA extracted from blood samples of the patient, her parents and sister. The 11 exons of the LHR gene were amplified by PCR and subjected to further single stranded conformation polymorphism (SSCP) analysis. Aberrant migration patterns were observed in exon 7. Upon sequencing, a homozygous T to G transversion was identified, resulting in a F194V substitution located in the extracellular domain. The parents and sister were heterozygous carriers of this mutation. Functional studies in transiently transfected COS-7 cells with the F194V LHR mutation showed the lack of cAMP production upon hCG stimulation, indicating complete inactivation of the receptor due to impaired trafficking of the receptor to the membrane. The mutation is located within a stretch of five amino acids Ala (A)-Phe (F)-Asn (N)-Gly (G)-Thr (T), highly conserved in glycoprotein hormone receptors. For the follicle-stimulating hormone (FSH) receptor (FSHR) loss-of-function mutations have been allocated to this region, a homozygous A189V mutation resulting in a resistant ovary syndrome and impaired spermatogenesis and a heterozygous N191I mutation with no apparent phenotype. Further mutational and functional analysis of the AFN region in the LHR and FSHR revealed that the integrity of this amino acid sequence is crucial for receptor function.

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“…Genomic DNA was purified using the Nucleon Kit (Herolab, Braunschweig, Germany). Exons 1-11 of the LHR gene were amplified using the primers and cycling conditions described by Atger et al (5). Each PCR sample (25 L) contained 10 nmol/L Tris-HCl (pH 8.3), 50 nmol/L KCl, 0.01% gelatin, 2 nmol/L MgCl 2 , 0.2 mmol/L deoxy-NTPs, 2 U Taq polymerase (Promega Corp., Heidelberg, Germany), 100 mmol/L primer, and 200 ng DNA.…”

Section: Dna Isolation and Pcrmentioning

confidence: 99%

Male Hypogonadism Caused by Homozygous Deletion of Exon 10 of the Luteinizing Hormone (LH) Receptor: Differential Action of Human Chorionic Gonadotropin and LH

Gromoll¹,

Eiholzer²,

Nieschlag³

et al. 2000

The Journal of Clinical Endocrinology & Metabolism

151

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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. (J Clin Endocrinol

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Structure of the human luteinizing hormone-choriogonadotropin receptor gene: unusual promoter and 5′ non-coding regions

Cited by 97 publications

References 45 publications

LH (Trp8Arg/Ile15Thr), LHR (insLQ) and FSHR (Asn680Ser) polymorphisms genotypic prevalence in women with endometriosis and infertility

LH (Trp8Arg/Ile15Thr), LHR (insLQ) and FSHR (Asn680Ser) polymorphisms genotypic prevalence in women with endometriosis and infertility

Homozygous mutation within the conserved Ala-Phe-Asn-Glu-Thr motif of exon 7 of the LH receptor causes male pseudohermaphroditism

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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