Structure, function and regulation of gonadotropin receptors – A perspective

Menon, K.M.J.; Menon, Bindu

doi:10.1016/j.mce.2012.01.021

Cited by 107 publications

(57 citation statements)

References 160 publications

(208 reference statements)

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“…In the ovaries, cAMP is of utmost importance being instrumental as a second messenger for the follicle stimulating hormone (FSH) and luteinising hormone (LH) receptors, and is central in growth and development of follicles in all stages (Conti 2002, Menon & Menon 2012.…”

Section: Introductionmentioning

confidence: 99%

Phosphodiesterases in the rat ovary: effect of cAMP in primordial follicles

2015

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Phosphodiesterases (PDEs) are important regulators of the intracellular cAMP concentration, which is a central second messenger that affects a multitude of intracellular functions. In the ovaries, cAMP exerts diverse functions, including regulation of ovulation and it has been suggested that augmented cAMP levels stimulate primordial follicle growth. The present study examined the gene expression, enzyme activity and immunolocalization of the different cAMP hydrolysing PDEs families in the rat ovary. Further, the effect of PDE4 inhibition on primordial follicle activation in cultured neonatal rat ovaries was also evaluated. We found varied expression of all eight families in the ovary with Pde7b and Pde8a having the highest expression each accounting for more than 20% of the total PDE mRNA. PDE4 accounted for 15-26% of the total PDE activity. Immunoreactive PDE11A was found in the oocytes and PDE2A in the corpora lutea. Incubating neonatal rat ovaries with PDE4 inhibitors did not increase primordial follicle activation or change the expression of the developing follicle markers Gdf9, Amh, Inha, the proliferation marker Mki67 or the primordial follicle marker Tmeff2. In addition, the cAMP analogue 8-bromo-cAMP did not increase AKT1 or FOXO3A phosphorylation associated with follicle activation or increase the expression of Kitlg known to be associated with follicle differentiation but did increase the Tmeff2, Mki67 and Inha expression in a dose-dependent manner. In conclusion, this study shows that both Pde7b and Pde8a are highly expressed in the rodent ovary and that PDE4 inhibition does not cause an increase in primordial follicle activation. Reproduction (2015) 150 11-20

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Section: Introductionmentioning

confidence: 99%

Phosphodiesterases in the rat ovary: effect of cAMP in primordial follicles

2015

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“…FSH receptor (FSHR) and LH receptor (LHR) are members of a novel family of G-protein-coupled receptors and their genes are located on chromosome 2p21 [2]. Recently, significant new information has emerged about the structure, mechanisms of activation, expression and genetic mutations of these receptors [3]. Mutations can be activating or inactivating, and descriptions of only 10 FSHR-inactivating mutations and one activating mutation have been published.…”

Section: Introductionmentioning

confidence: 99%

Alterations of the FSH and LH receptor genes and evaluation of sperm ultrastructure in men with idiopathic hypergonadotropic hypogonadism

Collodel

Cantara

Cairano

et al. 2013

J Assist Reprod Genet

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Purpose Gonadotropins, interacting with their gonadal receptors, play a key role in sexual development, reproductive functions and metabolism. In this study we performed the genetic analysis of FSHR and LHR and semen investigation in 14 infertile men with normal level of T and elevated levels of FSH and/or LH in the absence of other causes of infertility. Methods Sperm parameters were analysed following WHO (2010) guidelines and sperm morphology by Transmission Electron Microscopy (TEM) analysis mathematically elaborated. FSHR and LHR gene mutations have been searched by PCR technique, followed by DHPLC analysis and direct sequencing.Results In FSHR, we found no difference in the frequency between Ala or Thr at position 307, Ser was at codon 680 in all subjects. Three patients had an heterozygous mutation at codon 419. Three intronic polymorphisms (rs2091787, rs6708637, rs1922464) were significantly found compared to controls; the single allele frequency and the odds ratio were calculated. Two new variants: the Cys338Arg and the Gln123Glu were detected in two different patients. Regarding LHR, three patients were heterozygous for the known variant Glu354Lys and two for Ile374Thr. Intronic polymorphisms were not identified. A new variant, the Val144Ile was found. By the routine semen analysis, variable seminal conditions in this group of patients was observed, on the contrary TEM data mathematically elaborated showed a homogeneous decrease in fertility index and increase in sperm pathologies such as apoptosis and immaturity. Conclusions The obtained results suggest that a deeper examination of spermatozoa, achieved by the use of more powerful tools such as TEM or molecular analysis, are advisable in patients with hypergonadotropic hypogonadism.

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“…Receptors may also trans-activate other receptors and combined mutations could affect this process adding to the overall complexity of this mechanism [28]. This association between these two portions of the receptor not only contributes to the complex structure function relationship but also to the impact a mutation in each segment may have on the overall receptor function [29,30].…”

Section: P I F F C H L S C L Q S T S Y H S N Q Lmentioning

confidence: 99%

A novel compound heterozygous mutation of the luteinizing hormone receptor –implications for fertility

Mitri

Bentov

Behan

et al. 2014

J Assist Reprod Genet

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The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) belongs to the family of G-protein coupled receptors and binds both luteinizing hormone (LH) and human chorionic gonadotropin (hCG). Ligand-receptor interaction mediates a downstream cascade of events which is essential for ovulation in women, and expression of the male phenotype in men. The human LHCGR gene consists of 11exons and 10 introns. Homozygous and compound heterozygous mutations may inactivate the receptor by altering its structure and subsequent function. Herein we reported a novel, compound heterozgygous inactivating LHCGR mutation in a woman who presented with secondary infertility, having previously carried to term a donor oocyte pregnancy. A 27 bp deletion was detected in exon I at amino acid number 12. This mutation involved the signal peptide region, which is important for protein targeting, maturation and cellular expression. Another mutation involving a 2 base pair (thymine and cytosine) deletion was detected in exon 11 at amino acid number 586. This deletion produced a frameshift resulting in a premature stop codon and a truncated protein. An XY sibling with the same mutations was phenotypically female and misdiagnosed as complete androgen insensitivity syndrome. Other unaffected family members were genetically tested and carried one of the two mutations.

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Structure, function and regulation of gonadotropin receptors – A perspective

Cited by 107 publications

References 160 publications

Phosphodiesterases in the rat ovary: effect of cAMP in primordial follicles

Phosphodiesterases in the rat ovary: effect of cAMP in primordial follicles

Alterations of the FSH and LH receptor genes and evaluation of sperm ultrastructure in men with idiopathic hypergonadotropic hypogonadism

A novel compound heterozygous mutation of the luteinizing hormone receptor –implications for fertility

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