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Serotonin induces parathyroid hormone-related protein in goat mammary gland.

ABSTRACT: During lactation, large amounts of calcium are exported from the mammary gland into milk to ensure skeletal growth of the offspring. Recent studies revealed that serotonin (5-HT) is essential to stimulate skeletal calcium resorption for milk synthesis. Our objective was to explore the correlation between circulating 5-HT and serum calcium and parathyroid hormone-related protein (PTHrP) concentrations around parturition in dairy goats. We also investigated the effect of 5-HT on PTHrP expression in cultured primary goat mammary epithelial cells (GMEC). Blood samples of multiparous Guanzhong dairy goats were collected on day -5 to 3 postpartum for analysis of serum concentrations of calcium, 5-HT, and PTHrP. Results revealed that from day -3 to 0 postpartum serum calcium and 5-HT concentrations decreased progressively, but serum PTHrP concentration only had a sharp drop in the postpartum period sampled. Correlation analysis of circulating 5-HT and serum calcium and PTHrP concentrations on day 1 and 2 postpartum revealed that low serum 5-HT concentration was positively correlated with serum total calcium or PTHrP concentration. By knocking down tryptophan hydroxylase-1 (TPH1) or adding 5-hydroxytryptophan (5-HTP) to decrease or increase the levels of 5-HT in GMEC, we observed that 5-HTP increased PTHrP expression in a dose-dependent manner and siTPH1 decreased PTHrP protein expression. Furthermore, 5-HT increased mRNA abundance of calcium-sensing receptor (CaSR) in a dose-dependent manner and decreased the expression of plasma membrane Ca2+ ATPase-1 (PMCA1). Taken together, 5-HT seems to induce PTHrP expression in goat mammary cells during and after parturition. These findings suggest that increasing 5-HT biosynthesis could be a potential therapeutic target for prevention of hypocalcemia in dairy goats.

SUBMITTER: Zang WJ

PROVIDER: S-EPMC6093522 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Serotonin induces parathyroid hormone-related protein in goat mammary gland.

Zang W J WJ Li H H Zhang Z F ZF QuZhen R R CuoMu Y Z YZ Zhang D K DK Luo J J Loor J J JJ Zheng H L HL

Journal of animal science 20180401 3

During lactation, large amounts of calcium are exported from the mammary gland into milk to ensure skeletal growth of the offspring. Recent studies revealed that serotonin (5-HT) is essential to stimulate skeletal calcium resorption for milk synthesis. Our objective was to explore the correlation between circulating 5-HT and serum calcium and parathyroid hormone-related protein (PTHrP) concentrations around parturition in dairy goats. We also investigated the effect of 5-HT on PTHrP expression i ...[more]

PMID: 29617866

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Project description:Disorders related to parathyroid hormone (PTH) resistance and PTH signaling pathway impairment are historically classified under the term of pseudohypoparathyroidism (PHP). The disease was first described and named by Fuller Albright and colleagues in 1942. Albright hereditary osteodystrophy (AHO) is described as an associated clinical entity with PHP, characterized by brachydactyly, subcutaneous ossifications, round face, short stature and a stocky build. The classification of PHP is further divided into PHP-Ia, pseudo-PHP (pPHP), PHP-Ib, PHP-Ic and PHP-II according to the presence or absence of AHO, together with an in vivo response to exogenous PTH and the measurement of Gs? protein activity in peripheral erythrocyte membranes in vitro. However, PHP classification fails to differentiate all patients with different clinical and molecular findings for PHP subtypes and classification become more complicated with more recent molecular characterization and new forms having been identified. So far, new classifications have been established by the EuroPHP network to cover all disorders of the PTH receptor and its signaling pathway. Inactivating PTH/PTH-related protein signaling disorder (iPPSD) is the new name proposed for a group of these disorders and which can be further divided into subtypes - iPPSD1 to iPPSD6. These are termed, starting from PTH receptor inactivation mutation (Eiken and Blomstrand dysplasia) as iPPSD1, inactivating Gs? mutations (PHP-Ia, PHP-Ic and pPHP) as iPPSD2, loss of methylation of GNAS DMRs (PHP-Ib) as iPPSD3, PRKAR1A mutations (acrodysostosis type 1) as iPPSD4, PDE4D mutations (acrodysostosis type 2) as iPPSD5 and PDE3A mutations (autosomal dominant hypertension with brachydactyly) as iPPSD6. iPPSDx is reserved for unknown molecular defects and iPPSDn+1 for new molecular defects which are yet to be described. With these new classifications, the aim is to clarify the borders of each different subtype of disease and make the classification according to molecular pathology. The iPPSD group is designed to be expandable and new classifications will readily fit into it as necessary.

Project description:Mesenchymal stem cells have been widely used in the treatment of various chronic diseases. The objective of this survey was to evaluate the therapeutic and regenerative potential of stem cells from adipose tissue (ASCs) in the milk production recovery repair of tissue injury in mastitis goats treated with antimicrobial agents prior to cell therapy. After the diagnosis of mastitis and treatment with gentamicin, eight lactating goats were selected for cellular and subsequent therapy, physical-chemical analysis of milk, ultrasonographic and histopathological examinations. The ASCs were taken from the subcutaneous fat of a young goat cultivated in vitro, marked with Qdots-655 and injected in the left mammary gland, being the right mammary gland used as the control. After 30 days the ultrasonographic and histopathological analyzes were repeated and, in the first lactation period, the physical-chemical analysis of the milk was reapeated. Before the cellular therapy, the physical-chemical quality of the milk was compromised and the ultrasonographic and histopathological analysis revealed a chronic inflammatory process and fibrous tissue. The marking of the ASCs with Qdots enabled the tracking, by fluorescence microscopy (BX41-OLYMPUS), in the mammary tissue. In the ASCs therapy, cultures showed high cellularity and characteristics favorable to preclinical studies; with the therapy the physical-chemical parameters of the milk, fat, protein, temperature and pH showed significant differences among the groups; five animals treated with ASCs reconstituted the functionality of the gland and the connective tissue reduced in quantity and inflammatory infiltrate cells. ASCs have potential for the possible regeneration of fibrous mastitis lesions in the mammary gland, however, it would be necessary to increase injection time for the histopathological analysis, since the reconstitution of the glandular acini within the assessed period was not finalized. ASCs can be used to reestablish milk production in goat with chronic mastitis repair mammary lesions, with potential to be a promising clinical alternative for animal rehabilitation for productivity.

Dataset Information

Serotonin induces parathyroid hormone-related protein in goat mammary gland.

Publications

Serotonin induces parathyroid hormone-related protein in goat mammary gland.

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