Two human menopausal gonadotrophin (hMG) preparations display different early signaling in vitro
| Autor: | Maria Teresa Villani, Clara Lazzaretti, Elia Paradiso, M. Varani, Kim Jonas, Livio Casarini, Manuela Simoni, Simonetta Tagliavini, Daria Morini, Beatrice Melli, Laura Riccetti, Tommaso Trenti, Riccardo Benevelli, Samantha Sperduti, Angela Falbo |
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| Přispěvatelé: | Department of Biomedical, Metabolic and Neural Sciences [Modena], Università degli Studi di Modena e Reggio Emilia, Azienda USL Modena, Arcispedale Santa Maria Nuova (ASMN), King‘s College London, Azienda Ospedaleria Universitaria di Modena, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
LH Embryology medicine.medical_specialty ART FSH gonadotropin hCG hMG endocrine system medicine.drug_class [SDV]Life Sciences [q-bio] 030209 endocrinology & metabolism Biology Chorionic Gonadotropin 03 medical and health sciences 0302 clinical medicine In vivo Internal medicine Genetics medicine Humans Receptor Granulosa Lutein Cell Molecular Biology Immunoassay Obstetrics and Gynecology Cell Biology [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism 3. Good health 030104 developmental biology Endocrinology HEK293 Cells Reproductive Medicine Calcium Female Gonadotropin Signal transduction Follicle Stimulating Hormone Menopause Follicle-stimulating hormone receptor Intracellular Gonadotropins Developmental Biology Hormone Signal Transduction |
| Zdroj: | Molecular Human Reproduction Molecular Human Reproduction, Oxford University Press (OUP), 2020, 26 (12), pp.894-905. ⟨10.1093/molehr/gaaa070⟩ Casarini, L, Riccetti, L, Paradiso, E, Benevelli, R, Lazzaretti, C, Sperduti, S, Melli, B, Tagliavini, S, Varani, M, Trenti, T, Morini, D, Falbo, A, Villani, M T, Jonas, K C & Simoni, M 2020, ' Two human menopausal gonadotrophin (hMG) preparations display different early signaling in vitro ', MOLECULAR HUMAN REPRODUCTION, vol. 26, no. 12, pp. 894-905 . https://doi.org/10.1093/molehr/gaaa070 |
| ISSN: | 1360-9947 1460-2407 |
| DOI: | 10.1093/molehr/gaaa070⟩ |
| Popis: | Commercial hMG drugs are marketed for the treatment of infertility and consist of highly purified hormones acting on receptors expressed in target gonadal cells. Menopur® and Meriofert® are combined preparation of FSH and hCG and are compared in vitro herein. To this purpose, the molecular composition of the two drugs was analyzed by immunoassay. The formation of FSH receptor and LH/hCG receptor (FSHR; LHCGR) heteromer, intracellular Ca2+ and cAMP activation, β-arrestin 2 recruitment and the synthesis of progesterone and estradiol were evaluated in transfected HEK293 and human primary granulosa lutein cells treated by drugs administered within the pg-mg/ml concentration range. Molecular characterization revealed that Meriofert® has a higher FSH:hCG ratio than Menopur® which, in turn, displays the presence of LH molecules. While both drugs induced similar FSHR-LHCGR heteromeric formations and intracellular Ca2+ increase, Meriofert® had a higher potency than Menopur® in inducing a cAMP increase. Moreover, Meriofert® revealed a higher potency than Menopur® in recruiting β-arrestin 2, likely due to different FSH content modulating the tridimensional structure of FSHR-LHCGR-β-arrestin 2 complexes, as evidenced by a decrease in bioluminescence resonance energy transfer signal. This drug-specific activation of intracellular signaling pathways is consistent with the molecular composition of these preparations and impacts downstream progesterone and estradiol production, with Menopur® more potent than Meriofert® in inducing the synthesis of both the steroids. These findings are suggestive of distinct in-vivo activities of these preparations, but require cautious interpretation and further validation from clinical studies. |
| Databáze: | OpenAIRE |
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