Suppression of hypothalamic-pituitary-gonadal function by linzagolix in benign prostatic hyperplasia and polycystic ovary syndrome animal models
© 2023 John Wiley & Sons Australia, Ltd..
The hypothalamic-pituitary-gonadal (HPG) axis is an important regulatory mechanism involved primarily in the development and regulation of the reproductive systems. The suppression of the HPG axis by gonadotropin-releasing hormone (GnRH) analogues is expected to be effective for the treatment of sex hormone-dependent diseases, such as endometriosis, uterine fibroid, prostate cancer, benign prostatic hyperplasia (BPH) and polycystic ovary syndrome (PCOS). Despite the established involvement of GnRH signalling in these disorders, the therapeutic efficacy of small molecular GnRH antagonists for BPH and PCOS has not been adequately evaluated in non-clinical studies. Therefore, the purpose of the present study was to evaluate the potential of linzagolix, a small molecular GnRH antagonist, as a potential new treatment option for BPH and PCOS. Dogs and rats exhibiting normal prostates and dogs diagnosed with prostatic hyperplasia were used to evaluate the effects of linzagolix in BPH. The effects of linzagolix were also examined in a rat model of PCOS induced by repeated administration of letrozole, an aromatase inhibitor. Linzagolix reduced serum luteinizing hormone and testosterone levels in male rats and normal or BPH model dogs and suppressed prostate weight without testosterone depletion, suggesting the existence of an optimal therapeutic testosterone level for BPH treatment. In a PCOS rat model, linzagolix improved both insulin resistance and ovarian dysfunction. Treatment with linzagolix decreased follicle-stimulating hormone levels, but did not alter serum luteinizing hormone and testosterone levels. These results indicate that linzagolix may provide a new treatment option for GnRH-related disorders, such as BPH and PCOS.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:50 |
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| Enthalten in: |
Clinical and experimental pharmacology & physiology - 50(2023), 11 vom: 25. Nov., Seite 914-923 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tezuka, Motohiro [VerfasserIn] |
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| Links: |
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| Themen: |
Drug repositioning |
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| Anmerkungen: |
Date Revised 01.10.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1111/1440-1681.13817 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361207328 |
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| 520 | |a © 2023 John Wiley & Sons Australia, Ltd. | ||
| 520 | |a The hypothalamic-pituitary-gonadal (HPG) axis is an important regulatory mechanism involved primarily in the development and regulation of the reproductive systems. The suppression of the HPG axis by gonadotropin-releasing hormone (GnRH) analogues is expected to be effective for the treatment of sex hormone-dependent diseases, such as endometriosis, uterine fibroid, prostate cancer, benign prostatic hyperplasia (BPH) and polycystic ovary syndrome (PCOS). Despite the established involvement of GnRH signalling in these disorders, the therapeutic efficacy of small molecular GnRH antagonists for BPH and PCOS has not been adequately evaluated in non-clinical studies. Therefore, the purpose of the present study was to evaluate the potential of linzagolix, a small molecular GnRH antagonist, as a potential new treatment option for BPH and PCOS. Dogs and rats exhibiting normal prostates and dogs diagnosed with prostatic hyperplasia were used to evaluate the effects of linzagolix in BPH. The effects of linzagolix were also examined in a rat model of PCOS induced by repeated administration of letrozole, an aromatase inhibitor. Linzagolix reduced serum luteinizing hormone and testosterone levels in male rats and normal or BPH model dogs and suppressed prostate weight without testosterone depletion, suggesting the existence of an optimal therapeutic testosterone level for BPH treatment. In a PCOS rat model, linzagolix improved both insulin resistance and ovarian dysfunction. Treatment with linzagolix decreased follicle-stimulating hormone levels, but did not alter serum luteinizing hormone and testosterone levels. These results indicate that linzagolix may provide a new treatment option for GnRH-related disorders, such as BPH and PCOS | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Yonekubo-Awaka, Saori |e verfasserin |4 aut | |
| 700 | 1 | |a Tamai, Yasuaki |e verfasserin |4 aut | |
| 700 | 1 | |a Tsuchioka, Kumi |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Kaoru |e verfasserin |4 aut | |
| 700 | 1 | |a Kuramochi, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Tatemichi, Satoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Nagasawa, Tatsuya |e verfasserin |4 aut | |
| 700 | 1 | |a Kiguchi, Sumiyoshi |e verfasserin |4 aut | |
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