Greetings All,

Will add a few more important serotonin papers to the list.  The lead author in three of these papers is Laura L Hernandez from the University of Wisconsin-Madison, Department of Dairy Sciences.  Here in the U.S., Wisconsin is especially known for its dairy production.

Title:  Could Use of Selective Serotonin Reuptake Inhibitors During Lactation Cause Persistent Effects on Maternal Bone?  [Review article]

In:  Journal of Mammary Gland Biology and Neoplasia 2018 Jun;23(1-2):5-25. doi: 10.1007/s10911-018-9390-6. Epub 2018 Mar 30.

Authors:  Samantha R Weaver, Laura L Hernandez.

Abstract:  "The lactating mammary gland elegantly coordinates maternal homeostasis to provide calcium for milk. During lactation, the monoamine serotonin regulates the synthesis and release of various mammary gland-derived factors, such as parathyroid hormone-related protein (PTHrP), to stimulate bone resorption. Recent evidence suggests that bone mineral lost during prolonged lactation is not fully recovered following weaning, possibly putting women at increased risk of fracture or osteoporosis. Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants have also been associated with reduced bone mineral density and increased fracture risk. Therefore, SSRI exposure while breastfeeding may exacerbate lactational bone loss, compromising long-term bone health. Through an examination of serotonin and calcium homeostasis during lactation, lactational bone turnover and post-weaning recovery of bone mineral, and the effect of peripartum depression and SSRI on the mammary gland and bone, this review will discuss the hypothesis that peripartum SSRI exposure causes persistent reductions in bone mineral density through mammary-derived PTHrP signaling with bone.  Keywords: Selective Serotonin Reuptake Inhibitor (SSRI); bone; lactation; serotonin."

Abstract only:  https://link.springer.com/article/10.1007%2Fs10911-018-9390-6



Title:  Endocrine pathways to regulate calcium homeostasis around parturition and the prevention of hypocalcemia in periparturient dairy cows. [Review article]

In:  Animal:  An International Journal of Animal Bioscience 2020 Feb;14(2):330-338. doi: 10.1017/S1751731119001605. Epub 2019 Jul 24.

Authors:  L E Hernández-Castellano, L L Hernandez, R M Bruckmaier.

Abstract:  "Calcium homeostasis is crucial for the normal function of the organism. Parathyroid hormone, calcitriol and calcitonin play critical roles in the homeostatic regulation of calcium. Serotonin and prolactin have also been shown to be involved in the regulation of calcium homeostasis. In modern dairy cows, the endocrine pathways controlling calcium homeostasis during non-lactating and non-pregnant physiological states are unable to fully support the increased demand of calcium required for milk synthesis at the onset of lactation. This review describes different endocrine systems associated with the regulation of calcium homeostasis in mammalian species around parturition with special focus on dairy cows. Additionally, classic and novel strategies to reduce the incidence of hypocalcemia in parturient dairy cows are discussed.  Keywords: mammary gland; metabolic diseases; metabolism; mineral balance; transition period."

Abstract only:  https://www.cambridge.org/core/journals/animal/article/review-endocrine-pathways-to-regulate-calcium-homeostasis-around-parturition-and-the-prevention-of-hypocalcemia-in-periparturient-dairy-cows/976A30B49D2ED9D649FB83D925AED656



Title:  Serotonin and calcium homeostasis during the transition period.

In:  Domestic Animal Endocrinology 2016 Jul;56 Suppl:S147-54.

Authors:  S R Weaver, J Laporta, S A E Moore, L L Hernandez.

Abstract:  "The transition from pregnancy to lactation puts significant, sudden demands on maternal energy and calcium reserves. Although most mammals are able to effectively manage these metabolic adaptations, the lactating dairy cow is acutely susceptible to transition-related disorders because of the high amounts of milk being produced. Hypocalcemia is a common metabolic disorder that occurs at the onset of lactation. Hypocalcemia is also known to result in poor animal welfare conditions. In addition, cows that develop hypocalcemia are more susceptible to a host of other negative health outcomes. Different feeding tactics, including manipulating the dietary cation-anion difference and administering low-calcium diets, are commonly used preventative strategies. Despite these interventions, the incidence of hypocalcemia in the subclinical form is still as high as 25% to 30% in the United States dairy cow population, with a 5% to 10% incidence of clinical hypocalcemia. In addition, although there are various effective treatments in place, they are administered only after the cow has become noticeably ill, at which point there is already significant metabolic damage. This emphasizes the need for developing alternative prevention strategies, with the monoamine serotonin implicated as a potential therapeutic target. Our research in rodents has shown that serotonin is critical for the induction of mammary parathyroid hormone-related protein, which is necessary for the mobilization of bone tissue and subsequent restoration of maternal calcium stores during lactation. We have shown that circulating serotonin concentrations are positively correlated with serum total calcium on the first day of lactation in dairy cattle. Administration of serotonin's immediate precursor through feeding, injection, or infusion to various mammalian species has been shown to increase circulating serotonin concentrations, with positive effects on other components of maternal metabolism. Most recently, preliminary data suggest that manipulation of the serotonergic axis precalving may positively affect postcalving calcium dynamics. Combined, our research suggests a potential mechanism by which serotonin acts on the mammary gland to maintain circulating maternal calcium concentrations. Further research into serotonin's potential as a therapeutic target could contribute significantly as a preventive strategy against hypocalcemia in early lactation dairy cows.  Keywords: Calcium; Dairy cow; Hypocalcemia; Serotonin."

Abstract only:    https://www.sciencedirect.com/science/article/pii/S0739724015001277?via%3Dihub


Title:  Serotonin as a homeostatic regulator of lactation.  (Lisa Marasco also provided this citation in her recent Lactnet post on serotonin)

In:  Domestic Animal Endocrinology 2012 Aug;43(2):161-70.

Authors:  R J Collier, L L Hernandez, N D Horseman.

Abstract:  "Serotonin (5-HT), a neurotransmitter produced in mammary epithelial cells (MECs), acts via autocrine–paracrine mechanisms on MECs to regulate milk secretion in a variety of species. Recent studies in dairy cows reported that 5-HT ligands affect milk yield and composition. We determined the mRNA expression of bovine 5-HT receptor (5-HTR) subtypes in bovine mammary tissue (BMT) and cultured bovine MECs. We then used pharmacologic agents to evaluate functional activities of 5-HTR subtypes. The mRNAs for five receptor isoforms (5-HTR1B, 5-HTR2A, 5-HTR2B, 5-HTR4, and 5-HTR7) were identified by conventional reverse transcription PCR, real-time PCR, and in situ hybridization in BMT. In addition to luminal MEC expression, 5-HTR4 was expressed in myoepithelium, and 5-HTR1B, HTR2A, and HTR2B were expressed in small mammary blood vessels. Studies to date report that there are multiple 5-HTR isoforms in mammary tissue of rodents, humans, and cattle. Inhibition of the 5-HT reuptake transporter with selective 5-HT reuptake inhibitors (SSRIs) disrupted tight junctions and decreased milk protein mRNA expression in mouse, human, and bovine mammary cells. Selective 5-HT reuptake inhibitors act to increase the cellular exposure to 5-HT by preventing reuptake of 5-HT by the cell and eventual degradation. Increasing 5-HT concentration in milk via inhibiting its reuptake (SSRI), or by increasing the precursor for 5-HT synthesis 5-hydroxytryptophan, accelerated decline in milk synthesis at dry-off. We conclude that the 5-HT system in mammary tissue acts as a homeostatic regulator of lactation."

Abstract only:  https://www.sciencedirect.com/science/article/pii/S0739724012000483?via%3Dihub


The above-mentioned impact of SSRIs on maternal bone mineral density during lactation is particularly sobering.  SSRIs are often prescribed to treat depression, among other approaches.  The Infant Risk Center's page on Non-Drug Treatments for Depression is written by Kathleen Kendall Tackett at Texas Tech University School of Medicine.  https://www.infantrisk.com/content/non-drug-treatments-depression

With kind regards,

Debbie

Debra Swank, RN BSN IBCLC
Program Director
MoreThanReflexes Education
Elkins, West Virginia USA
tel 304.619.1433
http://www.MoreThanReflexes.org

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