Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002453 (amenorrhea)
 6,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have characterized a circulating inhibitor of FSH receptor binding found in two patients with hypergonadotropic amenorrhea and myasthenia gravis. The inhibitor behaves as an immunoglobulin according to several criteria, including precipitation by 30% ammonium sulfate, migration on DEAE-cellulose chromatography, specific binding to protein A-Sepharose, characterization as a 7S protein in sucrose density gradients, and immunoprecipitation with specific antihuman immunoglobulin G. Evidence suggests that these antibodies are directed at determinants on or near the FSH receptor, and they may be responsible for the observed clinical FSH resistance.
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PMID:Inhibition of follicle-stimulating hormone receptor binding by circulating immunoglobulins. 628 Dec 95

Mutations of gonadotropin beta subunits or gonadotropin receptors are involved in some reproductive diseases leading to alterations of pubertal maturation or infertility. Homozygous inactivation of LH results in absence of pubertal maturation and hypogonadism in the male, whereas inactivation of FSH causes primary amenorrhea in females. Mutations of the gonadotropin receptors are classified into activating (the receptor is also active in the absence of the hormone: gain-of-function mutations) and inactivating types (the receptor is not properly processed and/or the hormone cannot bind: loss-of-function mutations). Activating mutations of the LH receptor have been described in familiar and sporadic forms of male-limited pseudoprecocious puberty, whereas they do not express any phenotype in females. The only activating mutation of the FSH receptor described to date was found in a hypophysectomized man who was fertile despite undetectable serum gonadotropin levels; the effects of constitutive FSH receptor activity occurring with normal pituitary function are not known. Homozygous inactivations of the LH and FSH receptor invariably lead to amenorrhea in genotypically female subjects. In males, inactivation of the LH receptor in its more severe form results in a clinical picture similar to the syndrome of complete androgen resistance, but milder forms of hypoandrogenization have been described as well. The clinical consequences of homozygous inactivation of the FSH receptor in males are associated with subfertility. Finally, polymorphic variants of both the gonadotropin LH and the FSH receptor are present in the normal population.
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PMID:Molecular pathophysiology of the pituitary-gonadal axis. 936 74

The gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) bind specific receptors, members of the G protein-coupled receptor superfamily. Mutations of gonadotropin receptors are classified into activating (constitutively active or gain-of-function mutations) and inactivating (loss-of-function mutations). Activating mutations of the LH receptor have been described in familial and sporadic forms of male-limited pseudoprecocious puberty, whereas they do not appear to have any particular phenotype in females. The only activating mutation of the FSH receptor described to date was found in a hypophysectomized man who was fertile despite undetectable serum gonadotropin levels; the effects of constitutive FSH receptor activity in the context of normal pituitary function are not known. Homozygous inactivating mutations of the LH and FSH receptor invariably lead to amenorrhea in genotypical female subjects. In males, inactivation of the LH receptor in its more severe form results in a clinical picture similar to the syndrome of complete androgen resistance, but milder forms of hypoandrogenization have been described as well. In males, homozygous inactivation of the FSH receptor can also be associated with infertility. Finally, polymorphic variants of the FSH receptor are present in the normal population.
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PMID:Molecular pathophysiology and clinical manifestations of gonadotropin receptor defects. 961 88

A cDNA was cloned from human testis cDNA library by the use of rat FSH receptor cDNA as a probe. Transformation of 293 cells with the cloned cDNA led to expression of specific human FSH binding sites with high affinity (Kd: 1.5 x 10(-9) M), ligand dose-dependent production of cAMP and promotion of phosphatidyl inositol turnover, indicating that the cloned cDNA must encode a human FSH receptor. Northern blot analysis using human ovarian tissues revealed a high expression of mRNA at the stage of early follicular phase, but not luteal phase. Cross-linking of ligand with the expressed human FSH receptor showed that the molecular mass of the receptor should be 76 kDa, consistent with the estimated size of deduced amino acid sequence from the cloned cDNA. A polymorphism was found at 680th amino acid Ser or Asn, in the C-terminal region of the receptor although the influence of this difference upon the receptor function was not determined obviously in this study yet. The incidence of the polymorphism in the C-terminal region was not significantly correlated to the reproductive failures in 70 female cases of endometriosis, hyperprolactinemia, amenorrhea, PCOD or POF. However, elucidation of the structure and function in human FSH receptor using the cDNA will be applicable to diagnosis of some clinical cases associated with abnormal FSH receptor gene in the future.
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PMID:[cDNA cloning of human testicular follicle-stimulating hormone receptor and analysis of its in vitro function]. 1003 19

Inactivating mutations of the FSH receptor (FSHR) are known to cause ovarian failure with amenorrhea and infertility in women. The first mutation identified in the FSHR gene was a missense mutation (566C-->T, predicting Ala189Val transition) found in several Finnish patients with primary amenorrhea due to ovarian failure. Only five additional, partially or totally inactivating, mutations of the FSHR have been reported. Here, we report a novel FSHR mutation, 1255G-->A, in a Finnish female with primary amenorrhea. The patient was a compound heterozygote for two mutations in the FSHR gene: 566C-->T, the Finnish founder mutation, and 1255G-->A, a previously unidentified mutation. The new mutation is located in exon 10 in the second transmembrane stretch of the FSHR, and it predicts an Ala419Thr change in the protein structure. In functional testing, the mutation was shown to have minimal effect on ligand binding capacity and affinity, but it almost totally abolished the cAMP second messenger response. Neither of the two FSHR mutations (566C-->T or1255G-->A) was identified in 40 other Finnish patients with premature ovarian failure. Based on this and previous studies, FSHR mutations remain a rare cause of ovarian failure.
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PMID:A Novel mutation in the FSH receptor inhibiting signal transduction and causing primary ovarian failure. 1188 79

The median age at menopause in Western populations of women is approximately 51 years. While very late (i.e., after 54 years) menopause is exceedingly uncommon, a sizeable minority of women experience cessation of ovarian function at or prior to age 45. By convention, menopause that occurs at ages 40-45 is considered "early" and occurs in about 5% of women. Premature ovarian failure (POF) is reserved for the approximately 1% of women who experience hypergonadotropic amenorrhea prior to age 40 years. POF represents the end stage of a variety of disorders that result in the loss of ovarian follicles. Depending upon the age at diagnosis, the probability of a genetic, autoimmune, or idiopathic cause will be more or less likely. Two functioning X chromosomes appear necessary for normal ovarian function. The most obvious genetic cause of POF is Turner Syndrome, in which a complete or near-complete loss of the second X chromosome occurs. Turner Syndrome typically results in the most severe and irreversible POF, often clinically evident prior to menarche. Typically, in Turner Syndrome, menopause precedes menarche, and there is no evidence of ovarian function. However, cases with multiple tissues diagnosed as 45, X have been reported to result in ovarian function and even pregnancy. It is likely that mitigating factors, perhaps autosomal, can modify this most severe and irreversible cause of ovarian failure. Lesser degrees of ovarian failure have also been attributed to partial X chromosome deletions and milder degrees of X chromosome mosaicism. Fragile X syndrome is another example of mild POF that can be linked to disorders of the X chromosome. Other genetic defects are believed to cause POF, yet their prevalence has been difficult to determine. The localization of the gene for the blepharophimosis/ptosis/POF Syndrome has been recently reported, yet this finding has not been seen commonly in POF. Other genetic syndromes including POF await elucidation. Many transgenic "knock-out" animals have been created with deficient ovarian function. Most interesting along these lines is the heterozygous FSH receptor knock-out, which exhibits a reduced follicle reserve and early ovarian depletion. Application of this knowledge and translation of these transgenic experiments into elucidation of clinical disease has been difficult, but represents an area of tremendous potential progress in the understanding of the pathogenesis of POF. Another approach to the genetics of POF has been to examine the genome of affected and unaffected individuals. The genetics appear to differ greatly depending upon the timing of the expression of the POF. For example, women with early menopause are more likely to possess the PVUII polymorphic allele for estrogen receptor alpha. Whether or not this polymorph is more common in women with earlier menopause, i.e., POF, is unclear. Pedigree data indicate that early menopause and premature menopause sort similarly within families. The only difference between women with true POF and those with early menopause may be in the timing of the expression of the syndrome, and not in the genetics. Population genetic approaches analyzing affected and unaffected individuals are underway in several research centers and represent another area of progress. Immune and other, idiopathic causes of POF await further clarification. It is clear that this is an area of great research potential. Understanding how ovaries fail may assist women with this disorder by facilitating the development of novel therapies. Additionally, such information will provide important clues about optimizing ovarian function in individuals without POF who are seeking extension of their reproductive life spans or fertility enhancement by other means.
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PMID:Mechanisms of premature ovarian failure. 1277 39

XX 'pure' gonadal dysgenesis is a disease related to Turner's syndrome. Patients of this disease are characterized by normal female external genitalia, bilateral streak gonads, amenorrhea and sexual infantilism. Recently, it has been reported that point mutations of the FSH receptor gene may be one of cause of this disease. The relationship between criminal behavior and XYY syndrome is still controversial. Increased incidence of disomic sperm in 47,XYY males has been reported by fluorescent in situ hybridization(FISH). Genetic counseling should be done when they undergo intracytoplasmic sperm injection.
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PMID:[XX 'pure' gonadal dysgenesis and XYY syndrome]. 1496 36

Premature ovarian failure (POF) is defined as the cessation of ovarian function under the age of 40 years and is characterized by amenorrhea, hypoestrogenism, and elevated serum gonadotropin concentrations. POF affects 1% of all women and occurs in approximately 0.1% before the age of 30 years. To date, mutations associated with POF have been identified in a small number of genes, including those encoding inhibin alpha (INHA), the FSH receptor and the LH/chorio gonadotrophin receptor. Germ cell specific genes such as Gdf9, Bmp15, and Rfpl4 may also play important roles in human oogenesis. Transcription factors that regulate oocyte gene expression in animal models and include Nobox, Taf4b, Figla, Lhx8, Sohlh1 and Sohlh2 are likely to be key mediators of fertility in humans. In this review, after summarizing the general background on human POF, we focus on insights gained from the animal models with regards to mammalian folliculogenesis. Studies in animal models provide new candidate genes for ovarian failure in humans.
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PMID:Candidate genes for premature ovarian failure. 1730 37

Polycystic ovary syndrome (PCOS) is an endocrine disorder and the criteria are specified by hyperandrogenism, oligomenorrhea or amenorrhea and polycystic ovary morphology. Follicle stimulating hormone (FSH) has effects on oogenesis and follicle development. Several polymorphisms of FSH receptor (FSHR) are related to primary amenorrhea, hypoplastic ovary, and high serum levels of FSH. Thus, an increase in FSH level leads to follicle maturation and proliferation of granulosa cells. The aim of this study was to determine whether Ser680Asn and Ala307Thr polymorphisms of FSHR were associated with the clinical features of PCOS in a Korean population. PCOS patients (n=235) and control subjects (n=128) in the reproductive age were recruited from the Fertility Center of CHA General Hospital in Seoul, Korea. For Ser680Asn and Ala307Thr polymorphisms in FSHR, frequency of respective genotypes was measured and statistical analysis was performed. Haplotype analysis between Ser680Asn and Ala307Thr was also performed. We found that the Ser680Asn of FSHR is associated with PCOS (p=0.0195, OR=1.66). However, in case of Ala307Thr, the variant is negligible and is not associated with PCOS (p=0.6963, OR=1.08). In haplotype analysis, Ser680Asn and Ala307Thr polymorphisms are not related with PCOS. Consequently, the Ser680Asn polymorphism of FSHR might significantly affect PCOS patients, separately from the Ala307Thr polymorphism.
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PMID:Genetic variations of follicle stimulating hormone receptor are associated with polycystic ovary syndrome. 2051 29

Recent studies suggest that bone marrow stem cells (BMSCs) are promising grafts to treat a variety of diseases, including reproductive dysfunction. Primary ovarian failure is characterized by amenorrhea and infertility in a normal karyotype female, with an elevated serum level of follicle-stimulating hormone (FSH) and a decrease level of estrogen caused by a mutation in FSH receptor (FSHR) gene. Currently, there is no effective treatment for this condition. The phenotype of FSHR (-/-) mouse, FORKO (follitropin receptor knockout), is a suitable model to study ovarian failure in humans. Female FORKO mice have elevated FSH, decreased estrogen levels, are sterile because of the absence of folliculogenesis, and display thin uteri and small nonfunctional ovaries. In this study, we determined the effects of BMSC transplantation on reproductive physiology in this animal model. Twenty four hours post BMSC transplantation, treated animals showed detectable estroidogeneic changes in daily vaginal smear. Significant increase in total body weight and reproductive organs was observed in treated animals. Hemotoxylin and eosin (H&E) evaluation of the ovaries demonstrated significant increase in both the maturation and the total number of the follicles in treated animals. The FSH dropped to 40-50% and estrogen increased 4-5.5 times in the serum of treated animals compared to controls. The FSHR mRNA was detected in the ovaries of treated animals. Our results show that intravenously injected BMSCs were able to reach the ovaries of FORKO mice, differentiate and express FHSR gene, make FSHR responsive to FSH, resume estrogen hormone production, and restore folliculogenesis.
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PMID:Bone marrow transplantation restores follicular maturation and steroid hormones production in a mouse model for primary ovarian failure. 2241 75


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