Feeding 5-hydroxy-l-tryptophan during the transition from pregnancy to lactation increases calcium mobilization from bone in rats

Laporta, Jimena; Peters, Tonia L.; Weaver, Samantha R.; Merriman, Kathryn E.; Hernández, Laura

doi:10.1016/j.domaniend.2013.01.005

Cited by 58 publications

(98 citation statements)

References 41 publications

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“…The decrease in circulating Ca concentrations observed in the present study is in contrast to previous work in rodents where dietary 5-HTP supplementation increased circulating Ca and PTHrP concentrations (Laporta et al 2013a). One plausible explanation for this is that in the present experiment, blood samples were collected during the 2 h post-infusion period, whereas in the previous rodent experiments, blood samples for measuring Ca and PTHrP in response to 5-HTP administration were collected after several days and up to 2 weeks after treatment (Laporta et al 2013a(Laporta et al , 2014b. This suggests that physiological responses to increased serotonin concentrations are different depending on the time point that is evaluated post-treatment.…”

Section: Discussioncontrasting

confidence: 99%

“…This implies that 5-HTP treatment shifts Ca from maternal circulation to other tissues, for example, the mammary gland, seeing as it is not being excreted in the urine. Our previous work in mice demonstrated that serotonin is responsible for increasing Ca pumps in the mammary gland and secretion into milk (Laporta et al 2013a(Laporta et al , 2014a. The decrease in circulating Ca concentrations observed in the present study is in contrast to previous work in rodents where dietary 5-HTP supplementation increased circulating Ca and PTHrP concentrations (Laporta et al 2013a).…”

Section: Discussionmentioning

confidence: 99%

“…Our previous work in mice demonstrated that serotonin is responsible for increasing Ca pumps in the mammary gland and secretion into milk (Laporta et al 2013a(Laporta et al , 2014a. The decrease in circulating Ca concentrations observed in the present study is in contrast to previous work in rodents where dietary 5-HTP supplementation increased circulating Ca and PTHrP concentrations (Laporta et al 2013a). One plausible explanation for this is that in the present experiment, blood samples were collected during the 2 h post-infusion period, whereas in the previous rodent experiments, blood samples for measuring Ca and PTHrP in response to 5-HTP administration were collected after several days and up to 2 weeks after treatment (Laporta et al 2013a(Laporta et al , 2014b.…”

Section: Discussionmentioning

confidence: 99%

“…Quantitative PCR was conducted with the CFX96 Touch Real-Time PCR Detection System (BioRad) using SSoFast EvaGreen Supermix (no. 1725203, BioRad) as described previously (Laporta et al 2013a). We evaluated the hepatic expression of genes associated with glucose, fatty acid, and ketone metabolism, including: 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-COA), pyruvate carboxylase (PC), pyruvate dehydrogenase kinase, isozyme 4 (PDK4), glucose-6-phosphatase (G6P), carnitine palmitoyltransferase 1 (CPT1), acyl-CoA dehydrogenase, very long chain (ACADVL), peroxisome proliferator-activated receptor a (PPARa), and acyl-CoA oxidase 1, palmitoyl (ACOX1).…”

Section: Hepatic Gene Expressionmentioning

confidence: 99%

“…Serotonin is synthesized by the mammary gland in several species (Matsuda et al 2004, Hernandez et al 2009, and it regulates several aspects of mammary gland function, including milk protein gene expression, the induction of parathyroid hormone-related protein (PTHrP) production, and mammary gland Ca pumps and transport (Matsuda et al 2004, Hernandez et al 2012, Laporta et al 2013a, 2014a. The concept that the mammary gland acts as an endocrine organ that secretes PTHrP into the circulation as a signal to target tissues to regulate Ca supply to the milk during lactation is well accepted in rodents and humans (Wysolmerski 2010).…”

Section: Introductionmentioning

confidence: 99%

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Increasing serotonin concentrations alter calcium and energy metabolism in dairy cows

Laporta

Moore

Weaver

et al. 2015

Journal of Endocrinology

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A 4!4 Latin square design in which varied doses (0, 0.5, 1.0, and 1.5 mg/kg) of 5-hydroxy-L-tryptophan (5-HTP, a serotonin precursor) were intravenously infused into late-lactation, non-pregnant Holstein dairy cows was used to determine the effects of serotonin on calcium and energy metabolism. Infusion periods lasted 4 days, with a 5-day washout between periods. Cows were infused at a constant rate for 1 h each day. Blood was collected pre-and 5, 10, 30, 60, 90, and 120 min post-infusion, urine was collected pre-and post-infusion, and milk was collected daily. All of the 5-HTP doses increased systemic serotonin as compared to the 0 mg/kg dose, and the 1.0 and 1.5 mg/kg doses increased circulating glucose and non-esterified fatty acids (NEFA) and decreased beta-hydroxybutyrate (bHBA) concentrations. Treatment of cows with either 1.0 or 1.5 mg/kg 5-HTP doses decreased urine calcium elimination, and the 1.5 mg/kg dose increased milk calcium concentrations. No differences were detected in the heart rates, respiration rates, or body temperatures of the cows; however, manure scores and defecation frequency were affected. Indeed, cows that received 5-HTP defecated more, and the consistency of their manure was softer. Treatment of late-lactation dairy cows with 5-HTP improved energy metabolism, decreased loss of calcium into urine, and increased calcium secretion into milk. Further research should target the effects of increasing serotonin during the transition period to determine any benefits for post-parturient calcium and glucose metabolism.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Hepatic Gene Expressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increasing serotonin concentrations alter calcium and energy metabolism in dairy cows

Laporta

Moore

Weaver

et al. 2015

Journal of Endocrinology

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Serotonin and Serotonin Transport in the Regulation of Lactation

Marshall

Hernández

Horseman

2013

J Mammary Gland Biol Neoplasia

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Serotonin (5-HT), classically known as a neurotransmitter involved in regulating sleep, appetite, memory, sexual behavior, neuroendocrine function and mood is also synthesized in epithelial cells located in many organs throughout the body, including the mammary gland. The function of epithelial 5-HT is dependent on the expression of the 5-HT receptors in a particular system. The conventional components of a classic 5-HT system are found within the mammary gland; synthetic enzymes (tryptophan hydroxylase I, aromatic amino acid decarboxylase), several 5-HT receptors and the 5-HT reuptake transporter (SERT). In the mammary gland, two actions of 5-HT through two different 5-HT receptor subtypes have been described: negative feedback on milk synthesis and secretion, and stimulation of parathyroid hormone related-protein, a calcium-mobilizing hormone. As with neuronal systems, the regulation of 5-HT activity is multifactorial, but one seminal component is reuptake of 5-HT from the extracellular space following its release. Importantly, the wide availability of selective 5-HT reuptake inhibitors (SSRI) allows the manipulation of 5-HT activity in a biological system. Here, we review the role of 5-HT in mammary gland function, review the biochemistry, genetics and physiology of SERT, and discuss how SERT is vital to the function of the mammary gland.

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Could use of Selective Serotonin Reuptake Inhibitors During Lactation Cause Persistent Effects on Maternal Bone?

Weaver

Hernández

2018

J Mammary Gland Biol Neoplasia

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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.

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Feeding 5-hydroxy-l-tryptophan during the transition from pregnancy to lactation increases calcium mobilization from bone in rats

Cited by 58 publications

References 41 publications

Increasing serotonin concentrations alter calcium and energy metabolism in dairy cows

Increasing serotonin concentrations alter calcium and energy metabolism in dairy cows

Serotonin and Serotonin Transport in the Regulation of Lactation

Could use of Selective Serotonin Reuptake Inhibitors During Lactation Cause Persistent Effects on Maternal Bone?

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