ArticleMolecular endocrinology (Baltimore, Md.)2014
Serotonin regulates calcium homeostasis in lactation by epigenetic activation of hedgehog signaling.
Article in Molecular endocrinology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- Uterotropic response to the antidepressant fluoxetine (Prozac) is dependent on a functional serotonin transporter and circulating serotonin.Scientific reports · 2025Article
- The Pivotal Interaction Between Serotonin and Calcium Shifts in Lactating Pregnant Spanish Purebred Mares: The Aging Effect.Veterinary sciences · 2025Article
- Exploring the contribution of mammary-derived serotonin on liver and pancreas metabolism during lactation.PloS one · 2024Article
- The antidepressant fluoxetine (Prozac®) modulates serotonin signaling to alter maternal peripartum calcium homeostasis.Scientific reports · 2023Article
- Article
- Maternal serotonin: implications for the use of selective serotonin reuptake inhibitors during gestation†.Biology of reproduction · 2023Review
- The Serotonergic System and Bone Metabolism During Pregnancy and Lactation and the Implications of SSRI Use on the Maternal-Offspring Dyad.Journal of mammary gland biology and neoplasia · 2023Review
- 5-Hydroxytryptophan inhibits β-casein biosynthesis and promotes goat mammary epithelial cell apoptosis through the JAK2/STAT5a axis and the HTR7.Journal of animal science · 2023Article
- Fluoxetine treatment during the postpartal period may have short-term impacts on murine maternal skeletal physiology.Frontiers in pharmacology · 2023Article
- Crosstalk within a brain-breast-bone axis regulates mineral and skeletal metabolism during lactation.Frontiers in physiology · 2023Review
- Peripartal treatment with low-dose sertraline accelerates mammary gland involution and has minimal effects on maternal and offspring bone.Physiological reports · 2022Article
- Impact of Fluoxetine Treatment and Folic Acid Supplementation on the Mammary Gland Transcriptome During Peak Lactation.Frontiers in pharmacology · 2022Article
- Histological and transcriptomic analysis of adipose and muscle of dairy calves supplemented with 5-hydroxytryptophan.Scientific reports · 2021Article
- Elevated serotonin coordinates mammary metabolism in dairy cows.Physiological reports · 2021Article
- Article
- Serotonin regulates maternal calcium homeostasis during the perinatal period of sheep.Journal of animal science · 2019Article
- In utero and lactational exposure to the Selective Serotonin Reuptake Inhibitor fluoxetine compromises pup bones at weaning.Scientific reports · 2019Article
- Peripartum Fluoxetine Reduces Maternal Trabecular Bone After Weaning and Elevates Mammary Gland Serotonin and PTHrP.Endocrinology · 2018Article
- Could use of Selective Serotonin Reuptake Inhibitors During Lactation Cause Persistent Effects on Maternal Bone?Journal of mammary gland biology and neoplasia · 2018Review
- Serotonin induces parathyroid hormone-related protein in goat mammary gland.Journal of animal science · 2018Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Calcium homeostasis during lactation is critical for maternal and neonatal health. We previously showed that nonneuronal/peripheral serotonin [5-hydroxytryptamine (5-HT)] causes the lactating mammary gland to synthesize and secrete PTHrP in an acute fashion. Here, using a mouse model, we found that genetic inactivation of tryptophan hydroxylase 1 (Tph1), which catalyzes the rate-limiting step in peripheral 5-HT synthesis, reduced circulating and mammary PTHrP expression, osteoclast activity, and maternal circulating calcium concentrations during the transition from pregnancy to lactation. Tph1 inactivation also reduced sonic hedgehog signaling in the mammary gland during lactation. Each of these deficiencies was rescued by daily injections of 5-hydroxy-L-tryptophan (an immediate precursor of 5-HT) to Tph1-deficient dams. We used immortalized mouse embryonic fibroblasts to demonstrate that 5-HT induces PTHrP through a sonic hedgehog-dependent signal transduction mechanism. We also found that 5-HT altered DNA methylation of the Shh gene locus, leading to transcriptional initiation at an alternate start site and formation of a variant transcript in mouse embryonic fibroblasts in vitro and in mammary tissue in vivo. These results support a new paradigm of 5-HT-mediated Shh regulation involving DNA methylation remodeling and promoter switching. In addition to having immediate implications for lactation biology, identification and characterization of a novel functional regulatory relationship between nonneuronal 5-HT, hedgehog signaling, and PTHrP offers new avenues for the study of these important factors in development and disease.
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