Placental lactogens induce serotonin biosynthesis in a subset of mouse beta cells during pregnancy

Diabetologia. 2010 Dec;53(12):2589-99. doi: 10.1007/s00125-010-1913-7. Epub 2010 Oct 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gestational Age
  • Insulin-Secreting Cells / classification
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Placental Lactogen / pharmacology*
  • Placental Lactogen / physiology
  • Pregnancy / metabolism*
  • Serotonin / biosynthesis*
  • Tryptophan Hydroxylase / genetics
  • Tryptophan Hydroxylase / metabolism
  • Up-Regulation / drug effects

Substances

  • Serotonin
  • Placental Lactogen
  • Tryptophan Hydroxylase