Primary amenorrhoea and infertility due to a mutation in the β–subunit of follicle–stimulating hormone

Matthews, Charles H.; Borgato, Stefano; Beck‐Peccoz, Paolo; Adams, Matthew; Tone, Yukiko; Gambino, Giovanna; Casagrande, Stefania; Tedeschini, G.; Benedetti, A.; Chatterjee, Krishna

doi:10.1038/ng0993-83

Cited by 341 publications

(146 citation statements)

References 23 publications

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“…2). One of these involves a two base-pair deletion at codon 61 of the gene, causing a frame shift, premature stop and a truncation of the FSHb protein, rendering it completely inactive (Matthews et al 1993). The second mutant, Tyr76X, also causes truncation of the protein (Layman et al 2002) and in vitro expression of the mutant causes complete abrogation of both immuno-and bio-activity.…”

Section: Fshb Mutationsmentioning

confidence: 99%

An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms

Themmen¹

2005

Reproduction

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New information about mutations and polymorphisms in the genes for the gonadotrophins and their receptors has become available in the last few years. In this short review mutations and polymorphisms in gonadotrophins, their receptors and their patho-physiological effects and implications are discussed. An increasingly clear picture about the structure -function relationships of gonadotrophin action is emerging from the combining the types and the locations of the mutations with their phenotypic effects and the information about the crystal structure of these molecules.

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Section: Fshb Mutationsmentioning

confidence: 99%

An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms

Themmen¹

2005

Reproduction

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“…A very limited number of physiopathological situations associated with a lack of FSH secretion (Mathews et al 1993) or with FSHR genetic defects (Aittomaki et al 1995, Taipanainen et al 1997 have been reported in man. The recent report of FSH subunit as well as FSH receptor gene inactivation by homologous recombination in mice can be considered as a phenocopy of a receptor inactivating mutation (Kumar et al 1997, Sairam et al 1998.…”

Section: Discussionmentioning

confidence: 99%

Generating FSH antagonists and agonists through immunization against FSH receptor N-terminal decapeptides

Abdennebi¹,

Couture²,

Grebert³

et al. 1999

Journal of Molecular Endocrinology

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Follicle-stimulating hormone (FSH) via interaction with G-protein coupled specific receptors plays a central role in the control of gametogenesis in mammals of both sexes. In females, FSH is crucial for follicle growth, follicle maturation and ovulation. FSH receptors, together with luteinizing hormone-chorionic gonadotropin and thyrotropin receptors belong to a subfamily of structurally related receptors within the seven transmembrane receptor family. Among several other regions, the N-terminus of these receptors is believed to be responsible for important specific hormonereceptor contact sites. Recombinant filamentous phages displaying at their surface three overlapping N-terminal decapeptides of the FSH receptor, peptides A18-27, B25-34 and C29-38 were constructed. Ewes and female mice were immunized against the three FSH receptor (FSHR) recombinant phages. Immunoglobulins purified from immunized animals were analyzed for their biochemical properties on a Chinese hamster ovary cell line expressing the porcine FSH receptor. AntiA and antiB immunoglobulins (IgGs) behave as antagonists for 125 I-FSH binding and for FSHdependent cAMP production, while antiC IgGs did not compete for hormone binding. By contrast, antibodies against the C29-38 peptide displayed FSH agonist activity and stimulated the FSH receptor, whereas antiA and antiB IgGs did not. Furthermore, when the FSHR phages were used as peptidic vaccines, they induced a reversible inhibition of ovulation rate in ewes, and impaired fertility in female mice.

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“…FSH-β is located at 11p13, and mutations in this gene are reported in two women primary amenorrhea [60]. FSH receptor is crucial for recruitment of ovarian follicles and follicular maturation from and beyond the preantral stage [15,25].…”

Section: Autosomal Poi Genesmentioning

confidence: 99%

An update on primary ovarian insufficiency

Jin

Huang

2012

Sci. China Life Sci.

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Primary ovarian insufficiency (POI) occurs in about 1% of female population under the age of 40, leading to reproductive problems, an earlier encounter with menopausal symptoms, and complicated diseases. There are three presumable mechanisms involved in the development of POI, namely apoptosis acceleration, follicular maturation blocking and premature follicle activation, through the following studied causes: (i) chromosomal abnormalities or gene mutations: mostly involve X chromosome, such as FMR1 premutation; more and more potentially causal genes have been screened recently; (ii) metabolic disorders such as classic galactosaemia and 17-OH deficiency; (iii) autoimmune mediated ovarian damage: observed alone or with some certain autoimmune disorders and syndromes; but the specificity and sensitivity of antibodies towards ovary are still questionable; (iv) iatrogenic: radiotherapy or chemotherapy used in cancer treatment, as well as pelvic surgery with potential threat to ovaries' blood supply can directly damage ovarian function; (v) virus infection such as HIV and mumps; (vi) toxins and other environmental/lifestyle factors: cigarette smoking, toxins (e.g., 4-vinylcyclohexene diepoxide), and other environmental factors are associated with the development of POI. The etiology of a majority of POI cases is not identified, and is believed to be multifactorial. Strategies to POI include hormone replacement and infertility treatment. Assisted conception with donated oocytes has been proven to achieve pregnancy in POI women. Embryo cryopreservation, ovarian tissue cryopreservation and oocyte cryopreservation have been used to preserve ovarian reserve in women undergoing cancer treatments. Primary ovarian insufficiency (POI), commonly referred to as premature ovarian failure (POF), is defined as the occurrence of amenorrhea (for 4 months or more) before the age of 40 in women, accompanied with an increase of serum FSH to menopausal level (usually over 40 IU L 1 , obtained at least 1 month apart), and estradiol levels less than 50 pg mL 1 (which indicate hypoestrogenism) [1]. Primary ovarian insufficiency is first brought to light by Fuller Albright in 1942, who emphasized that the end stage of ovarian function is the primary defect rather than abnormality in gonadotropin secretion [2], and avoided the discomforting and inaccurate stressing on "failure", like death-sentence for ovarian function and conception.Menopause is a destined phase of women, which is expected to occur at around the age of (50±4) years in US women [3]. The age of 40 is two standard deviations below this average [4]. With an incidence of 1% in women under the age of 40, and 0.1% in women under the age of 30 [5], POI renders patients estrogen deficiency and anovulation, resulting in vasomotor symptoms (hot flashes and night sweats), atrophic vaginitis, dyspareunia, primary or secondary amenorrhea, and infertility. 76% of POI cases developed after normal puberty and establishment of regular menses [6]. Some of such conditions occur after stopping...

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Primary amenorrhoea and infertility due to a mutation in the β–subunit of follicle–stimulating hormone

Cited by 341 publications

References 23 publications

An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms

An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms

Generating FSH antagonists and agonists through immunization against FSH receptor N-terminal decapeptides

An update on primary ovarian insufficiency

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