Placental lactogens induce serotonin biosynthesis in a subset of mouse beta cells during pregnancy
| Autor: | Mikaela Granvik, G. de Faudeur, N. Binart, Frans Schuit, Katleen Lemaire, L. Van Lommel, J. Mallet, G. Vodjdani, Patrick Gilon, Nico Hendrickx, Anica Schraenen, P. In't Veld |
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| Přispěvatelé: | UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - SSS/IREC - Institut de recherche expérimentale et clinique |
| Jazyk: | angličtina |
| Předmět: |
endocrine system
Serotonin medicine.medical_specialty Insulin-Secreting Cells - classification drug effects metabolism Tryptophan hydroxylase Endocrinology Diabetes and Metabolism Gestational Age Biology Gene Expression Regulation Enzymologic Article Mice Islets of Langerhans Downregulation and upregulation Pregnancy Insulin-Secreting Cells Internal medicine Tph2 Tph1 medicine Internal Medicine Animals Tryptophan Hydroxylase - genetics metabolism Placental lactogen Receptor Cells Cultured Mice Knockout Fetus Placental Lactogen - pharmacology physiology Serotonin - biosynthesis Prolactin receptor Pregnancy - metabolism Embryo Mammalian medicine.disease Prolactin Up-Regulation Mice Inbred C57BL Endocrinology Beta cell heterogeneity Gene Expression Regulation Enzymologic - drug effects Female Up-Regulation - drug effects Beta cell |
| Zdroj: | Diabetologia Diabetologia, Vol. 53, no. 12, p. 2589-2599 (2010) |
| ISSN: | 0012-186X |
| DOI: | 10.1007/s00125-010-1913-7 |
| Popis: | Aims/hypothesis Upregulation of the functional beta cell mass is required to match the physiological demands of mother and fetus during pregnancy. This increase is dependent on placental lactogens (PLs) and prolactin receptors, but the mechanisms underlying these events are only partially understood. We studied the mRNA expression profile of mouse islets during pregnancy to gain a better insight into these changes. Methods RNA expression was measured ex vivo via microarrays and quantitative RT-PCR. In vivo observations were extended by in vitro models in which ovine PL was added to cultured mouse islets and MIN6 cells. Results mRNA encoding both isoforms of the rate-limiting enzyme of serotonin biosynthesis, tryptophan hydroxylase (TPH), i.e. Tph1 and Tph2, were strongly induced (fold change 25- to 200-fold) during pregnancy. This induction was mimicked by exposing islets or MIN6 cells to ovine PLs for 24 h and was dependent on janus kinase 2 and signal transducer and activator of transcription 5. Parallel to Tph1 mRNA and protein induction, islet serotonin content increased to a peak level that was 200-fold higher than basal. Interestingly, only a subpopulation of the beta cells was serotonin-positive in vitro and in vivo. The stored serotonin pool in pregnant islets and PL-treated MIN6 cells was rapidly released (turnover once every 2 h). Conclusions/interpretation A very strong lactogen-dependent upregulation of serotonin biosynthesis occurs in a subpopulation of mouse islet beta cells during pregnancy. Since the newly formed serotonin is rapidly released, this lactogen-induced beta cell function may serve local or endocrine tasks, the nature of which remains to be identified. Electronic supplementary material The online version of this article (doi:10.1007/s00125-010-1913-7) contains supplementary material, which is available to authorised users. |
| Databáze: | OpenAIRE |
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