Sandbox Reserved 1646
From Proteopedia
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The gonadotropin releasing hormone 1 receptor is located in the plasmic membrane of [https://en.wikipedia.org/wiki/Gonadotropic_cell pituitary gonadotrope cells] in the anterior pituitary, a major organ of the [https://en.wikipedia.org/wiki/Endocrine_system endocrine system] in the brain. It is activated by the [https://en.wikipedia.org/wiki/Gonadotropin-releasing_hormone gonadotropin releasing hormone (GnRH)] which acts upon GnRHRs as the key regulator of puberty and reproduction. This peptide hormone is produced in the hypothalamus but gets secreted and acts upon GnRHRs in the anterior pituitary to exert its effects on reproductive maturation. The activation of the receptor, associates with G-proteins, leads to the releasing of [https://en.wikipedia.org/wiki/Luteinizing_hormone gonadotropic luteinizing hormone (LH)] and [https://en.wikipedia.org/wiki/Follicle-stimulating_hormone follicle stimulating hormone (FSH)] by activating several signaling cascades. These pathways mainly corresponds to the inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG), MAPK, and adenyl cyclase pathways. <ref> DOI: 10.3892/or_00000525</ref>. | The gonadotropin releasing hormone 1 receptor is located in the plasmic membrane of [https://en.wikipedia.org/wiki/Gonadotropic_cell pituitary gonadotrope cells] in the anterior pituitary, a major organ of the [https://en.wikipedia.org/wiki/Endocrine_system endocrine system] in the brain. It is activated by the [https://en.wikipedia.org/wiki/Gonadotropin-releasing_hormone gonadotropin releasing hormone (GnRH)] which acts upon GnRHRs as the key regulator of puberty and reproduction. This peptide hormone is produced in the hypothalamus but gets secreted and acts upon GnRHRs in the anterior pituitary to exert its effects on reproductive maturation. The activation of the receptor, associates with G-proteins, leads to the releasing of [https://en.wikipedia.org/wiki/Luteinizing_hormone gonadotropic luteinizing hormone (LH)] and [https://en.wikipedia.org/wiki/Follicle-stimulating_hormone follicle stimulating hormone (FSH)] by activating several signaling cascades. These pathways mainly corresponds to the inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG), MAPK, and adenyl cyclase pathways. <ref> DOI: 10.3892/or_00000525</ref>. | ||
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| - | == Disease == | ||
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| - | A mutation or a dysfonctionnement of the receptor could cause diseases impacting the reproduction function. More generally, the dysfonctionnement of the pathways involving GnRH and its receptor leads to endocrine pathologies called [https://en.wikipedia.org/wiki/Hypogonadism hypogonadism]. <ref> DOI: 10.1016/j.cnur.2018.04.006</ref> It exits many types of hypogonadism but the one involving the mutation of the receptor is the [https://en.wikipedia.org/wiki/Isolated_hypogonadotropic_hypogonadism idiopatic hypogonadotropic hypogonadism (IHH)]. In this case, the mutation leads to failure of detectable ligand binding causing the decreased efficiency of the inisitol pathway and consequently leading to the decrease of the LH, FSH, and sex steroid secretions <ref>DOI 10.1210/jc.2003-031808</ref>. | ||
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| - | Moreover, the activity the pathways related to the receptor and its localisation can cause cancer. <ref>DOI: 10.1677/erc.1.00777</ref> | ||
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| - | == Relevance == | ||
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| - | The main uses of the couple GnRH - GnRHR in the medicine field are to cure hormone-dependent diseases and assisted reproductive techniques. For instance, an agonist of GnRH is used for fertility preservation as an alternative of cryopreservation <ref>DOI 10.1210/en.2013-1341</ref>. In addition it is a promising therapeutic target for the treatment of conditions including uterine fibroids <ref>DOI: 10.1080/17460441.2018.1417381</ref>, endometriosis <ref>DOI: 10.1080/14656566.2017.1359258</ref>, and prostate cancer <ref>DOI: 10.1002/pros.23360</ref>. | ||
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| - | Besides, concerning animals, the GnRH receptor could be a good target for contraception with a DNA vaccine <ref>DOI: 10.1007/s12033-018-0137-9</ref> | ||
==Structure == | ==Structure == | ||
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=== General structure === | === General structure === | ||
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The transition of different GPCR conformation states is known to be mediated by water molecules by rearranging the conserved hydrophilic network formed by conserved amino acids in different helices43 | The transition of different GPCR conformation states is known to be mediated by water molecules by rearranging the conserved hydrophilic network formed by conserved amino acids in different helices43 | ||
Different motifs have already been identified to be critical for signal transmission in GnH1R. Noteworthy the hydrophobic Y6.51-Y6.52(TM6)-W6.48-F6.44 motif in TM6 and residues F2726.40 and Y3237.53. | Different motifs have already been identified to be critical for signal transmission in GnH1R. Noteworthy the hydrophobic Y6.51-Y6.52(TM6)-W6.48-F6.44 motif in TM6 and residues F2726.40 and Y3237.53. | ||
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| + | ==Gonadotrophin releasing hormone== | ||
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| + | GnRH is a decapeptid that was isolated and characterised by the groups of A V Schally and R C L Guillemin, the 1977 Nobel laureates. | ||
| + | GnRH is the pivotal hypothalamic hormone regulating reproduction. Over 20 forms of the decapeptide have been identified in which the NH2- and COOH-terminal sequences, which are essential for receptor binding and activation, are conserved. | ||
| + | In most vertebrates there are at least two, and usually three, forms of GnRH. In mammals, there are two forms, GnRH I which regulates gonadotropin and GnRH II which appears to be a neuromodulator and stimulates sexual behaviour. | ||
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| + | ===Agonist=== | ||
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| + | ===Antagonist=== | ||
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| + | == Disease == | ||
| + | |||
| + | A mutation or a dysfonctionnement of the receptor could cause diseases impacting the reproduction function. More generally, the dysfonctionnement of the pathways involving GnRH and its receptor leads to endocrine pathologies called [https://en.wikipedia.org/wiki/Hypogonadism hypogonadism]. <ref> DOI: 10.1016/j.cnur.2018.04.006</ref> It exits many types of hypogonadism but the one involving the mutation of the receptor is the [https://en.wikipedia.org/wiki/Isolated_hypogonadotropic_hypogonadism idiopatic hypogonadotropic hypogonadism (IHH)]. In this case, the mutation leads to failure of detectable ligand binding causing the decreased efficiency of the inisitol pathway and consequently leading to the decrease of the LH, FSH, and sex steroid secretions <ref>DOI 10.1210/jc.2003-031808</ref>. | ||
| + | |||
| + | Moreover, the activity the pathways related to the receptor and its localisation can cause cancer. <ref>DOI: 10.1677/erc.1.00777</ref> | ||
| + | |||
| + | == Relevance == | ||
| + | |||
| + | The main uses of the couple GnRH - GnRHR in the medicine field are to cure hormone-dependent diseases and assisted reproductive techniques. For instance, an agonist of GnRH is used for fertility preservation as an alternative of cryopreservation <ref>DOI 10.1210/en.2013-1341</ref>. In addition it is a promising therapeutic target for the treatment of conditions including uterine fibroids <ref>DOI: 10.1080/17460441.2018.1417381</ref>, endometriosis <ref>DOI: 10.1080/14656566.2017.1359258</ref>, and prostate cancer <ref>DOI: 10.1002/pros.23360</ref>. | ||
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| + | GnRH agonists and antagonists also have promise as novel contraceptives. Indeed, concerning animals, the GnRH receptor could be a good target for contraception with a DNA vaccine <ref>DOI: 10.1007/s12033-018-0137-9</ref> | ||
<scene name='86/868179/Test1/1'>Test</scene> | <scene name='86/868179/Test1/1'>Test</scene> | ||
Revision as of 15:15, 23 January 2021
| This Sandbox is Reserved from 26/11/2020, through 26/11/2021 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1643 through Sandbox Reserved 1664. |
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Gonadotropin releasing hormone 1 receptor (GnRHR)
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