loading...| Preferred Name |
Polycystic Ovary Syndrome |
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| Synonyms |
PathwayType: signaling Description: Polycystic ovary syndrome (PCOS) is generally characterized by hyperandrogenemia, anovulation/oligoovulation, and polycystic ovary. Pathway is built manually using published studies. Organ: ovary Organ_System: reproductive system PMID: 12017544 Notes: Headnote: Polycystic ovary syndrome (PCOS) is generally characterized by hyperandrogenemia, anovulation/oligoovulation, and polycystic ovary. The origin of hyperandrogenemia arises from excessive luteinizing hormone (LH) stimulation of follicle theca cells. Signaling description: Gonadotropin-releasing hormone (GNRH1) has elevated amplitude of secretion in the pathology and provokes increased LH release from the pituitary. Insulin (INS), IGF1, and retinol enhance LH action by triggering the expression of steroidogenic enzymes including CYP11A1, CYP17A1, HSD3B2, and HSD17B1. INS also promotes LDLR synthesis in the theca cells. LDLR transports cholesterol, which is the substrate for hormone biosynthesis, into the cell. In the pathology, the hormone reduces the synthesis of IGFB1 and SHBG in the liver, thus providing free IGF1 and testosterone. The next step of steroidogenesis in women occurs in granulosa cells where testosterone and its derivatives are converted into estrogens. Normally, the conversion is promoted by CYP19A1. The lack of the enzyme due to a deficiency of stimulatory signals from FSH leads to androgen excess. In some cases, testosterone may be converted into dihydrotestosterone by elevated SRD5A1. Outcome effects: The excess of androgens, particularly dihydrotestosterone, explain hirsutism and acne in PCOS women. Elevated AMH, FST, inhibin complex, and estrogens prevent FSH signaling in granulosa cells disrupting not only estrogen production, but also blocking cell proliferation and differentiation, which are necessary for follicle maturation. The arrested signaling includes the PI3K, PKC, and PKA routes, which normally lead to proliferation and differentiation of granulosa cells. PLCB1 provokes Ca2+-dependent PKC activation and affects BRAF, which promotes the MAPK1/MAPK3 pathway. The pathway recruits CREB1, FOS, and SRF transcription factors, which initiate cell division. In addition, the MAPK1/MAPK3 pathway, along with PKA, promotes GATA4 activation. GATA4 and SRF are responsible for cell differentiation. Impaired FSH signaling prevents AKT1 activation, which normally inhibits FOXO1, a negative regulator of cell proliferation and differentiation. The excess of androgens bind to their intracellular receptor (AR) and trigger IGF1R appearance on granulosa cell surfaces. Elevated IGF1 binds to its receptor and induces PI3K activation. Further, PI3K promotes AKT1 phosphorylation of CDKN1B, BAD, and GSK3B leading to their inhibition. These proteins normally promote granulosa cell proliferation. Lastly, the arrested development of follicles at the small preantral follicle stage causes anovulation in PCOS and register as polycystic ovary at an ultrasound examination. Highlighted proteins: Entities with increased level of activity are highlighted in red, and entities with decreased level of activity are highlighted in blue. Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-7be51e51-17c2-4102-8e0e-f5388e272241 PMID: 21606667 PMID: 19078868 CellType: theca cell PMID: 16390494 NodeType: Pathway PMID: 18440223 CellType: granulosa cell Source: Diseases PMID: 20591140 |
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| ID |
urn:agi-pathway:uuid-7be51e51-17c2-4102-8e0e-f5388e272241 |
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| database_cross_reference |
PS:PathwayType PS:Description PS:Link PS:CellType PS:Organ_System PS:PMID PS:NodeType PS:Notes PS:Organ PS:Source |
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| has_exact_synonym |
PathwayType: signaling Description: Polycystic ovary syndrome (PCOS) is generally characterized by hyperandrogenemia, anovulation/oligoovulation, and polycystic ovary. Pathway is built manually using published studies. Organ: ovary Organ_System: reproductive system PMID: 12017544 Notes: Headnote: Polycystic ovary syndrome (PCOS) is generally characterized by hyperandrogenemia, anovulation/oligoovulation, and polycystic ovary. The origin of hyperandrogenemia arises from excessive luteinizing hormone (LH) stimulation of follicle theca cells. Signaling description: Gonadotropin-releasing hormone (GNRH1) has elevated amplitude of secretion in the pathology and provokes increased LH release from the pituitary. Insulin (INS), IGF1, and retinol enhance LH action by triggering the expression of steroidogenic enzymes including CYP11A1, CYP17A1, HSD3B2, and HSD17B1. INS also promotes LDLR synthesis in the theca cells. LDLR transports cholesterol, which is the substrate for hormone biosynthesis, into the cell. In the pathology, the hormone reduces the synthesis of IGFB1 and SHBG in the liver, thus providing free IGF1 and testosterone. The next step of steroidogenesis in women occurs in granulosa cells where testosterone and its derivatives are converted into estrogens. Normally, the conversion is promoted by CYP19A1. The lack of the enzyme due to a deficiency of stimulatory signals from FSH leads to androgen excess. In some cases, testosterone may be converted into dihydrotestosterone by elevated SRD5A1. Outcome effects: The excess of androgens, particularly dihydrotestosterone, explain hirsutism and acne in PCOS women. Elevated AMH, FST, inhibin complex, and estrogens prevent FSH signaling in granulosa cells disrupting not only estrogen production, but also blocking cell proliferation and differentiation, which are necessary for follicle maturation. The arrested signaling includes the PI3K, PKC, and PKA routes, which normally lead to proliferation and differentiation of granulosa cells. PLCB1 provokes Ca2+-dependent PKC activation and affects BRAF, which promotes the MAPK1/MAPK3 pathway. The pathway recruits CREB1, FOS, and SRF transcription factors, which initiate cell division. In addition, the MAPK1/MAPK3 pathway, along with PKA, promotes GATA4 activation. GATA4 and SRF are responsible for cell differentiation. Impaired FSH signaling prevents AKT1 activation, which normally inhibits FOXO1, a negative regulator of cell proliferation and differentiation. The excess of androgens bind to their intracellular receptor (AR) and trigger IGF1R appearance on granulosa cell surfaces. Elevated IGF1 binds to its receptor and induces PI3K activation. Further, PI3K promotes AKT1 phosphorylation of CDKN1B, BAD, and GSK3B leading to their inhibition. These proteins normally promote granulosa cell proliferation. Lastly, the arrested development of follicles at the small preantral follicle stage causes anovulation in PCOS and register as polycystic ovary at an ultrasound examination. Highlighted proteins: Entities with increased level of activity are highlighted in red, and entities with decreased level of activity are highlighted in blue. PMID: 21606667 PMID: 19078868 CellType: theca cell PMID: 16390494 NodeType: Pathway PMID: 18440223 CellType: granulosa cell Source: Diseases PMID: 20591140 |
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| id |
urn:agi-pathway:uuid-7be51e51-17c2-4102-8e0e-f5388e272241 |
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| label |
Polycystic Ovary Syndrome |
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| notation |
uuid-7be51e51-17c2-4102-8e0e-f5388e272241 |
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| prefLabel |
Polycystic Ovary Syndrome |
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| treeView |
urn:agi-folder:polycystic_ovary_syndrome urn:agi-folder:reproductive_system urn:agi-folder:p |
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| subClassOf |
urn:agi-folder:polycystic_ovary_syndrome urn:agi-folder:reproductive_system urn:agi-folder:p |