Placental adaptive up-regulation of calcium transport in wild-type mice is not driven by parathyroid hormone-related protein (PTHrP)

Placenta ◽  
2016 ◽  
Vol 45 ◽  
pp. 128
Author(s):  
Christina Hayward ◽  
Kirsty McIntyre ◽  
Colin Sibley ◽  
Susan Greenwood ◽  
Mark Dilworth
Keyword(s):  
Parathyroid Hormone ◽  
Calcium Transport ◽  
Related Protein ◽  
Wild Type ◽  
Parathyroid Hormone Related Protein

scholarly journals Parathyroid hormone-related protein regulates intestinal calcium transport in sea bream (Sparus auratus)

2006 ◽  
Vol 291 (5) ◽  
pp. R1499-R1506 ◽  
Author(s):  
Juan Fuentes ◽  
Joana Figueiredo ◽  
Deborah M. Power ◽  
Adelino V. M. Canário
Keyword(s):  
Parathyroid Hormone ◽  
Calcium Transport ◽  
Calcium Uptake ◽  
Sea Bream ◽  
Whole Body ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Intestinal Calcium Transport ◽  
Sparus Auratus

Parathyroid hormone-related protein (PTHrP) is a factor associated with normal development and physiology of the nervous, cardiovascular, immune, reproductive, and musculoskeletal systems in higher vertebrates. It also stimulates whole body calcium uptake in sea bream ( Sparus auratus) larvae with an estimated 60% coming from intestinal uptake in seawater. The present study investigated the role of PTHrP in the intestinal calcium transport in the sea bream in vitro. Unidirectional mucosal-to-serosal and serosal-to-mucosal 45Ca fluxes were measured in vitro in duodenum, hindgut, and rectum mounted in Ussing chambers. In symmetric conditions with the same saline, bathing apical and basolateral sides of the preparation addition of piscine PTHrP 1–34 (6 nM) to the serosal surface resulted in an increase in mucosal to serosal calcium fluxes in duodenum and hindgut and a reduction in serosal to mucosal in the rectum, indicating that different mechanisms are responsive to PTHrP along the intestine. In control asymmetric conditions, with serosal normal and mucosal bathed with a saline similar in composition to the intestinal fluid, there was a net increase in calcium uptake in all regions. The addition of 6 nM PTHrP 1–34 increased net calcium uptake two- to threefold in all regions. The stimulatory effect of PTHrP on net intestinal calcium absorption is consistent with a hypercalcemic role for the hormone. The results support the view that PTHrP, alone or in conjunction with recently identified PTH-like peptides, counteracts in vivo the hypocalcemic effects of stanniocalcin.

Cortisol, parathyroid hormone-related protein and the onset of calcium secretion by the mammary gland of the goat

1997 ◽  
Vol 64 (4) ◽  
pp. 633-636
Author(s):  
GORDON E. THOMPSON ◽  
S. KHAWAR ABBAS ◽  
CARL HOLT ◽  
ANTHONY D. CARE
Keyword(s):  
Mammary Gland ◽  
Parathyroid Hormone ◽  
Epithelial Cells ◽  
Tight Junctions ◽  
Calcium Transport ◽  
Extracellular Fluid ◽  
Secretory Cells ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Calcium Secretion

During lactogenesis in the goat, the onset of secretion of calcium into milk occurs at parturition (Thompson et al. 1995) at approximately the same time as the onset of secretion of parathyroid hormone-related protein (PTHrP) by the mammary gland (Ratcliffe et al. 1992); these events may be unrelated or PTHrP may be involved in calcium transport from blood to milk.Parturition in goats is initiated by fetal secretion of cortisol (Flint et al. 1978) and maternal secretion of cortisol also increases (Paterson & Linzell, 1971). Injecting cortisol locally into the sinus of a mammary gland of the late-pregnant goat when the tight junctions between secretory epithelial cells appear to be ‘loose’, and injectate can reach the basolateral surfaces of secretory cells, stimulates an early tightening of these junctions (Thompson, 1996) as occurs naturally at parturition. This tightening can be produced by an increased concentration of ionized calcium in the extracellular fluid of the gland (Neville & Peaker, 1981).The experiments reported here were undertaken to determine if cortisol injection stimulates the mammary gland to secrete both PTHrP and calcium before parturition.

scholarly journals Roles of Parathyroid Hormone-Related Protein (PTHrP) and Its Receptor (PTHR1) in Normal and Tumor Tissues: Focus on Their Roles in Osteosarcoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Awf A. Al-Khan ◽  
Noora R. Al Balushi ◽  
Samantha J. Richardson ◽  
Janine A. Danks
Keyword(s):  
Breast Cancer ◽  
Squamous Cell Carcinoma ◽  
Parathyroid Hormone ◽  
Survival Rate ◽  
Calcium Transport ◽  
Related Protein ◽  
Primary Bone Tumor ◽  
Parathyroid Hormone Related Protein ◽  
Tumor Tissues ◽  
Primary Bone

Osteosarcoma (OS) is the most common primary bone tumor and originates from bone forming mesenchymal cells and primarily affects children and adolescents. The 5-year survival rate for OS is 60 to 65%, with little improvement in prognosis during the last four decades. Studies have demonstrated the evolving roles of parathyroid hormone-related protein (PTHrP) and its receptor (PTHR1) in bone formation, bone remodeling, regulation of calcium transport from blood to milk, regulation of maternal calcium transport to the fetus and reabsorption of calcium in kidneys. These two molecules also play critical roles in the development, progression and metastasis of several tumors such as breast cancer, lung carcinoma, chondrosarcoma, squamous cell carcinoma, melanoma and OS. The protein expression of both PTHrP and PTHR1 have been demonstrated in OS, and their functions and proposed signaling pathways have been investigated yet their roles in OS have not been fully elucidated. This review aims to discuss the latest research with PTHrP and PTHR1 in OS tumorigenesis and possible mechanistic pathways.This review is dedicated to Professor Michael Day who died in May 2020 and was a very generous collaborator.

scholarly journals Parathyroid Hormone-Related Protein Is a Mitogenic and a Survival Factor of Mesangial Cells from Male Mice: Role of Intracrine and Paracrine Pathways

Endocrinology ◽  
2013 ◽  
Vol 154 (2) ◽  
pp. 853-864 ◽  
Author(s):  
Mazène Hochane ◽  
Denis Raison ◽  
Catherine Coquard ◽  
Olivier Imhoff ◽  
Thierry Massfelder ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Nuclear Localization ◽  
Signal Peptide ◽  
Mesangial Cells ◽  
Nuclear Localization Sequence ◽  
Related Protein ◽  
Wild Type ◽  
Parathyroid Hormone Related Protein ◽  
Proliferation And Apoptosis ◽  
Localization Sequence

Glomerulonephritis is characterized by the proliferation and apoptosis of mesangial cells (MC). The parathyroid-hormone related protein (PTHrP) is a locally active cytokine that affects these phenomena in many cell types, through either paracrine or intracrine pathways. The aim of this study was to evaluate the effect of both PTHrP pathways on MC proliferation and apoptosis. In vitro studies were based on MC from male transgenic mice allowing PTHrP-gene excision by a CreLoxP system. MC were also transfected with different PTHrP constructs: wild type PTHrP, PTHrP devoid of its signal peptide, or of its nuclear localization sequence. The results showed that PTHrP deletion in MC reduced their proliferation even in the presence of serum and increased their apoptosis when serum-deprived. PTH1R activation by PTHrP(1–36) or PTH(1–34) had no effect on proliferation but improved MC survival. Transfection of MC with PTHrP devoid of its signal peptide significantly increased their proliferation and minimally reduced their apoptosis. Overexpression of PTHrP devoid of its nuclear localization sequence protected cells from apoptosis without changing their proliferation. Wild type PTHrP transfection conferred both mitogenic and survival effects, which seem independent of midregion and C-terminal PTHrP fragments. PTHrP-induced MC proliferation was associated with p27Kip1 down-regulation and c-Myc/E2F1 up-regulation. PTHrP increased MC survival through the activation of cAMP/protein kinase A and PI3-K/Akt pathways. These results reveal that PTHrP is a cytokine of multiple roles in MC, acting as a mitogenic factor only through an intracrine pathway, and reducing apoptosis mainly through the paracrine pathway. Thus, PTHrP appears as a probable actor in MC injuries.

scholarly journals Parathyroid hormone-related protein(1-34) in gestational fluids and release from human gestational tissues

2000 ◽  
Vol 165 (3) ◽  
pp. 657-662 ◽  
Author(s):  
W Farrugia ◽  
PW Ho ◽  
GE Rice ◽  
JM Moseley ◽  
M Permezel ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Amniotic Fluid ◽  
G Protein ◽  
Calcium Transport ◽  
Fetal Membranes ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Gestational Tissues ◽  
Epithelial Growth ◽  
Stimulation Of

Parathyroid hormone-related protein (PTHrP) is present in fetal and gestational tissues, in which its proposed roles include stimulation of epithelial growth and differentiation, vasodilatation of the uteroplacental vasculature, relaxation of uterine muscle and stimulation of placental calcium transport. The aim of this study was to determine whether the release of PTHrP from gestational tissue explants was tissue specific. In addition, PTHrP concentrations were measured in maternal plasma, umbilical artery and vein plasma, and amniotic fluid from term, uncomplicated pregnancies before the onset of labour. PTHrP was detected in low concentrations in the mother, fetus and placental tissue. Amniotic fluid had ten times the PTHrP concentration compared with that in the maternal or fetal circulations. Using late pregnant human gestational tissues in an in vitro explant system, we found that amnion over placenta, choriodecidua, reflected amnion, and placenta released PTHrP into culture medium in progressively greater amounts over 24 h (P<0.05). This release was not associated with a loss of cell membrane integrity, as indicated by measurement of the intracellular enzyme, lactate dehydrogenase, in the incubation media. After 24 h incubation, the fetal membranes released significantly (P<0.05) greater amounts of PTHrP than did the placenta (placenta 3. 7+/-0.5 pmol PTHrP/g protein). Amnion over placenta released significantly more PTHrP (139.3+/- 43.1 pmol PTHrP/g protein) than did reflected amnion (29.0+/-8.3 pmol PTHrP/g protein) (P<0.05). This study unequivocally demonstrated that human gestational tissues release PTHrP and it was concluded that the main contributors to PTHrP in amniotic fluid were the human fetal membranes, particularly amnion over placenta. Fetal membrane-derived and amniotic fluid PTHrP are proposed to have stimulatory effects on epithelial growth and differentiation in fetal lung, gut, skin and hair follicles and paracrine effects on placental vascular tone and calcium transport.

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