Normal Pregnancy-Induced Islet Beta Cell Proliferation in Mouse Models That Are Deficient in Serotonin-Signaling.

During mouse pregnancy placental lactogens stimulate prolactin receptors on pancreatic islet beta cells to induce expression of the tryptophan hydroxylase Tph1 , resulting in the synthesis and secretion of serotonin. Presently, the functional relevance of this phenomenon is unclear. One hypothesis is that serotonin-induced activation of 5-HT _2B receptors on beta cells stimulates beta cell proliferation during pregnancy. We tested this hypothesis via three different mouse models: (i) total Tph1 KO mice, (ii) 129P2/OlaHsd mice, which are incompetent to upregulate islet Tph1 during pregnancy, whereas Tph1 is normally expressed in the intestine, mammary glands, and placenta, and (iii) Htr2b -deficient mice. We observed normal pregnancy-induced levels of beta cell proliferation in total Tph1 KO mice, 129P2/OlaHsd mice, and in Htr2b ^-/- mice. The three studied mouse models indicate that islet serotonin production and its signaling via 5-HT _2B receptors are not required for the wave of beta cell proliferation that occurs during normal mouse pregnancy.