Functional characterization of a natural variant of luteinizing hormone

Wu, Liao; Goh, H. H.; Roy, A.C.

doi:10.1007/s00439-002-0781-8

Cited by 12 publications

(6 citation statements)

References 39 publications

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“…Variant LH b is undetectable in a radioreceptor assay compared with the wild-type hormone [8] and it has lower receptor-binding activity [15]. Inactivating human LH b mutation results in absence or decreased number of Leydig cells [6] because LH is necessary for normal development of Leydig cells.…”

Section: Discussionmentioning

confidence: 99%

Fertile Eunuch Syndrome with the Mutations (Trp8Arg and Ile15Thr) in the .BETA. Subunit of Luteinizing Hormone

Shiraishi

Naito²

2003

Endocr J

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Abstract. Fertile eunuch syndrome is caused by isolated LH deficiency, but its pathophysiology still remains controversial. We report a case of fertile eunuch syndrome with homozygous Trp8Arg and Ile15Thr mutations in the LH b subunit gene. An 18-year-old man was admitted to our hospital for hypogonadism. Examination of genitalia revealed Tanner G1PH1, whereas both testes were elastically palpated and developed up to 18 ml. Endocrinological evaluations revealed normogonadotropic hypogonadism and there were normal responses after GnRH and hCG stimulation. Intratesticular testosterone concentration was almost normal (1.34 × 10 3 ng/g). By PCR direct sequencing, homozygous Trp (8) Arg and Ile (15) Thr mutations in exon 2 of LH b were detected. Normal virilization and improved semen parameters were achieved after hCG supplementation. To our knowledge, this is the first case of fertile eunuch syndrome with homozygous Trp (8) Arg and Ile (15) Thr mutations in b subunit of LH gene.

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Section: Discussionmentioning

confidence: 99%

Fertile Eunuch Syndrome with the Mutations (Trp8Arg and Ile15Thr) in the .BETA. Subunit of Luteinizing Hormone

Shiraishi

Naito²

2003

Endocr J

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“…It has also been suggested that hyposensitivity to FSH may be caused by an abnormal variant of the FSH receptor that reduces sensitivity to the receptor [70]. Mutations in the genes coding for LH [71-75] and the LH receptor [76-78] have been identified and these mutations may play a role in the cause of infertility, as well as influence the success or failure of fertility treatment. Further, it has been suggested that assessing serum androgen levels prior to initiation of COS may be beneficial for the selection of gonadotropin starting doses.…”

Section: Discussionmentioning

confidence: 99%

Individualised controlled ovarian stimulation (iCOS): maximising success rates for assisted reproductive technology patients

Bosch

Ezcurra

2011

Reprod Biol Endocrinol

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BackgroundIn the last two decades, pregnancy rates for patients undergoing in-vitro fertilisation (IVF) have significantly increased. Some of the major advances responsible for this improvement were the introduction of controlled ovarian stimulation (COS) for the induction of multiple follicle development, and the utilisation of mid-luteal gonadotropin-releasing hormone agonists to achieve pituitary down-regulation and full control of the cycle. As a result, a combination of a gonadotropin-releasing hormone agonist with high doses (150-450 IU/day) of recombinant follicle-stimulating hormone has become the current standard approach for ovarian stimulation. However, given the heterogeneity of patients embarking on IVF, and the fact that many different drugs can be used alone or in different combinations (generating multiple potential protocols of controlled ovarian stimulation), we consider the need to identify special populations of patients and adapt treatment protocols accordingly, and to implement a more individualised approach to COS.DiscussionStudies on mild, minimal and natural IVF cycles have yielded promising results, but have focused on fresh embryo transfers and included relatively young patient populations who generally have the potential for more favourable outcomes. The efficacy of these protocols in patients with a poorer prognosis remains to be tested. When comparing protocols for COS, it is important to think beyond current primary endpoints, and to consider the ideal quality and quantity of oocytes and embryos being produced per stimulated patient, in order to achieve a pregnancy. We should also focus on the cumulative pregnancy rate, which is based on outcomes from fresh and frozen embryos from the same cycle of stimulation. Individualised COS (iCOS) determined by the use of biomarkers to test ovarian reserve has the potential to optimise outcomes and reduce safety issues by adapting treatment protocols according to each patient's specific characteristics. As new objective endocrine, paracrine, functional and/or genetic biomarkers of response are developed, iCOS can be refined further still, and this will be a significant step towards a personalised approach for IVF.ConclusionsA variety of COS protocols have been adopted, with mixed success, but no single approach is appropriate for all patients within a given population. We suggest that treatment protocols should be adapted for individual patients through iCOS; this approach promises to be one of the first steps towards implementing personalised medicine in reproductive science.

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“…Both FGFR1 and PROKR2 were found to coincide with the same LHB variant (Gly122Ser) in 2 patients (Table 1 ). This LHB variant have been reported to significantly affect the binding ability of luteinizing hormone to its receptor and greatly reduce the biopotency for steroidogenesis of luteinizing hormone (Liao et al, 2002). No direct obvious correlation was observed between number of variants in oligogenic inheritance and spermatogenesis outcomes, partially because of relatively small number of patients.…”

Section: Oligogenic Patternmentioning

confidence: 96%

Genetic profiles and three-year follow-up study of Chinese males with congenital hypogonadotropic hypogonadism

Zhang

Gao

et al. 2020

Preprint

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Genotypes-phenotypes correlation and treatment outcomes for 73 Chinese CHH male patients was performed in this study. Patients self-selected one of the four treatments: pulsatile Gonadorelin® pump, cyclical gonadotropins therapy, human menopausal gonadotropin monotherapy, or testosterone replacement treatment. Clinical assessments were performed every 3 months for 3 years. Baseline clinical features, spermatogenesis and secondary sexual development outcomes were analyzed. Whole exome sequencing identified 63 variants in 52 patients (70%), 18 of which were novel. Variants on FGFR1, PROKR2, CHD7, ANOS1 and NSMF gene were 10 (15.87%), 10 (15.87%), 7(11.11%), 5(7.93%) and 5(7.93%) respectively. Some null variants could lead to severe clinical manifestations than missense variants on FGFR1 and CHD7. The Lasso regression model for spermatogenic failure risk showed that cryptorchidism history, abnormal epididymis or prostate, lower basal LH and peak-LH post Triptore-lin® stimulation were significant predictors. Approximately, 30% normosmic patients defined by simple olfactory assessment showed olfactory nerve center maldevelopment with nasal sinus MRI. The severity of reproductive system was attributed to spermatogenesis that could be predicted by nomogram model. No direct correlation was observed between candidate genes and spermatogenic outcome, however, the clinical severity is partially related with specific variants, and clinical features might in turn affect the treatment efficacy.

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Functional characterization of a natural variant of luteinizing hormone

Cited by 12 publications

References 39 publications

Fertile Eunuch Syndrome with the Mutations (Trp8Arg and Ile15Thr) in the .BETA. Subunit of Luteinizing Hormone

Fertile Eunuch Syndrome with the Mutations (Trp8Arg and Ile15Thr) in the .BETA. Subunit of Luteinizing Hormone

Individualised controlled ovarian stimulation (iCOS): maximising success rates for assisted reproductive technology patients

Genetic profiles and three-year follow-up study of Chinese males with congenital hypogonadotropic hypogonadism

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