Parathyroid hormone-related protein regulates intestinal calcium transport in sea bream (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.

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Parathyroid hormone-related protein and calcium regulation in vitamin D-deficient sea bream (Sparus auratus)

Journal of Endocrinology ◽

10.1677/joe-06-0164 ◽

2007 ◽

Vol 193 (3) ◽

pp. 473-480 ◽

Cited By ~ 10

Author(s):

W Abbink ◽

X M Hang ◽

P M Guerreiro ◽

F A T Spanings ◽

H A Ross ◽

...

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Calcium Influx ◽

Sea Bream ◽

Whole Body ◽

Calcium Balance ◽

Related Protein ◽

Deficient Diet ◽

Parathyroid Hormone Related Protein ◽

Sparus Auratus

Gilthead sea bream (Sparus auratus L.) were fed a vitamin D-deficient diet for 22 weeks. Growth rate, whole body mineral pools and calcium balance were determined. Plasma parathyroid hormone-related protein (PTHrP) and calcitriol levels were assessed. Expression of mRNA for pthrp and pth1r was quantified in gills and hypophysis. Fish on vitamin D-deficient diet (D− fish) showed reduced growth and lower calcium turnover (calcium influx, efflux and accumulation rates decreased) and unaltered plasma calcium levels. Plasma calcitriol levels became undetectable, PTHrP levels decreased in the D− fish. In controls, a significant increase in plasma PTHrP level over time was seen, i.e. it increased with body mass. Relationships were found between plasma PTHrP and the whole body pools of calcium, phosphorus and magnesium, indicative of a role for PTHrP in bone development. Expression of pthrp and pth1r mRNA was down-regulated in the hypophysis of D−fish, whereas in gill tissue, pthrp and pth1r mRNA were up-regulated. We conclude that lower pthrp mRNA expression and plasma values in D− fish reflect lower turnover of PTHrP under conditions of hampered growth; up-regulation of pthrp mRNA in gills indicate compensatory paracrine activity of PTHrP during calcitriol deficiency to guarantee well-regulated branchial calcium uptake. This is the first report to document a relation between PTHrP and calcitriol in fish.

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Parathyroid hormone-related protein-stanniocalcin antagonism in regulation of bicarbonate secretion and calcium precipitation in a marine fish intestine

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00378.2009 ◽

2010 ◽

Vol 299 (1) ◽

pp. R150-R158 ◽

Cited By ~ 20

Author(s):

Juan Fuentes ◽

Deborah M. Power ◽

Adelino V. M. Canário

Keyword(s):

Parathyroid Hormone ◽

Marine Fish ◽

Calcium Uptake ◽

Sea Bream ◽

Bicarbonate Secretion ◽

Related Protein ◽

Calcium Efflux ◽

Parathyroid Hormone Related Protein ◽

Calcium Availability ◽

Calcium Precipitation

Bicarbonate secretion in the intestine (duodenum) of marine fish has been suggested to play a major role in regulation of calcium availability for uptake. However, while the end process may lead to carbonate precipitation, regulation of transport of calcium and/or bicarbonate may actually result in fine-tuning of calcium availability for transport. To test this hypothesis, sea bream ( Sparus auratus ) duodenal preparations were mounted in Ussing-type chambers and the effect of parathyroid hormone-related protein (PTHrP) and stanniocalcin 1 (STC 1) on the control of intestinal bicarbonate secretion and calcium transport was analyzed. As expected, PTHrP increased net calcium uptake, as a result of an increase of calcium uptake without changes in calcium efflux. In contrast, purified sea bream STC 1 caused a minor decrease of calcium uptake and a two- to threefold increase in calcium efflux. As a result, STC 1 was able to invert the calcium flux from net calcium uptake to net calcium loss, which is in keeping with its known actions as a hypocalcemic factor. Furthermore, both PTHrP and STC 1 regulate intestinal bicarbonate secretion. PTHrP increased calcium uptake and simultaneously reduced the single factor that induces calcium precipitation, bicarbonate secretion. In contrast, STC 1, while reversing the calcium net flux to make it secretory, promoted intestinal bicarbonate secretion, both actions directed to decrease the calcium gradient across the epithelium and promote immobilization in the form of bicarbonate in the intestinal lumen. Together our results provide robust evidence to support an antagonistic action of PTHrP and STC 1 in the fine control of movements of both calcium and bicarbonate in the intestine of seawater fish.

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CYP27A1 expression in gilthead sea bream (Sparus auratus, L.): effects of calcitriol and parathyroid hormone-related protein

Journal of Endocrinology ◽

10.1677/joe-07-0566 ◽

2007 ◽

Vol 196 (3) ◽

pp. 625-635 ◽

Cited By ~ 3

Author(s):

Gideon S Bevelander ◽

Elsa S L C Pinto ◽

Adelino V M Canario ◽

Tom Spanings ◽

Gert Flik

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Gilthead Sea Bream ◽

Sea Bream ◽

Vitamin D Metabolites ◽

Related Protein ◽

Vitamin D Metabolism ◽

Parathyroid Hormone Related Protein ◽

25 Hydroxy Vitamin D ◽

Sparus Auratus

Little is known about vitamin D metabolism in fishes. Several reports have shown hydroxylase activities in various organs to produce vitamin D metabolites, but the enzymes involved have not been isolated or characterized. We isolated and characterized a renal mitochondrial hydroxylase, CYP27A1, that governs vitamin D metabolism in gilthead sea bream, Sparus auratus. The enzyme is highly expressed in kidney and to a far lesser extent in liver. When treated with 25-hydroxy vitamin D or calcitriol, the kidney responded differentially and time dependently with CYP27A1 mRNA expression levels. This response substantiates a role for CYP27A1 in fish vitamin D metabolism. This notion is strengthened by upregulation of CYP27A1 in sea bream treated with parathyroid hormone-related protein (PTHrP), and suggests an original role for PTHrP in calcitriol-regulated processes n fish similar to the role of PTH in mammalian vitamin D-dependent processes.

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Production and characterisation of gilthead sea bream (Sparus auratus) recombinant parathyroid hormone related protein

General and Comparative Endocrinology ◽

10.1016/j.ygcen.2005.02.020 ◽

2005 ◽

Vol 143 (1) ◽

pp. 57-65 ◽

Cited By ~ 7

Author(s):

L. Anjos ◽

J. Rotllant ◽

P.M. Guerreiro ◽

X. Hang ◽

A.V.M. Canario ◽

...

Keyword(s):

Parathyroid Hormone ◽

Gilthead Sea Bream ◽

Sea Bream ◽

Related Protein ◽

Parathyroid Hormone Related Protein ◽

Sparus Auratus

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In vitro model of parathyroid hormone-related protein secretion from mammary cells isolated from lactating cows

Domestic Animal Endocrinology ◽

10.1016/0739-7240(96)00070-7 ◽

1996 ◽

Vol 13 (5) ◽

pp. 399-410 ◽

Cited By ~ 7

Author(s):

H. Okada ◽

F.L. Schanbacher ◽

L.K. McCauley ◽

M.T. Weckmann ◽

C.C. Capen ◽

...

Keyword(s):

Parathyroid Hormone ◽

Protein Secretion ◽

In Vitro Model ◽

Mammary Cells ◽

Related Protein ◽

Lactating Cows ◽

Parathyroid Hormone Related Protein ◽

Vitro Model

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Regulation of calcium balance in the sturgeon Acipenser naccarii: a role for PTHrP

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00203.2007 ◽

2007 ◽

Vol 293 (2) ◽

pp. R884-R893 ◽

Cited By ~ 11

Author(s):

Juan Fuentes ◽

Christophe Haond ◽

Pedro M. Guerreiro ◽

Nádia Silva ◽

Deborah M. Power ◽

...

Keyword(s):

Calcium Transport ◽

Calcium Uptake ◽

Dietary Calcium ◽

Calcium Deficiency ◽

Cell Number ◽

The Body ◽

Whole Body ◽

Calcium Balance ◽

Parathyroid Hormone Related Protein ◽

Juvenile Sturgeon

Calcium regulation in sturgeon is of special interest because they are a representative of the ancient fishes possessing mainly cartilaginous skeletons and a supposedly low calcium demand. The present study aimed to characterize the effect of a chronic absence of dietary calcium and the effect of parathyroid hormone-related protein (PTHrPA) (1-34) ( 7 ) on calcium balance in juvenile sturgeon ( Acipenser naccarii). At rest, sturgeon juveniles are in net positive calcium balance, since whole body calcium uptake is significantly higher than efflux and calcium accumulates in the body. To study the importance of dietary calcium, the sturgeon were kept on a calcium-free diet for 8 wk. This manipulation impaired growth as measured by failure to gain weight or increase in length and indicates that dietary calcium is important for growth in sturgeon. An increased whole body calcium uptake partially compensated dietary calcium deficiency and was associated with increased gill chloride cell number in lamellae and filaments in parallel with increased gill Na+K+-ATPase activity. In addition, a single injection of piscine PTHrP(1-34) significantly increased whole body calcium uptake and decreased whole body calcium efflux. Administration of PTHrP significantly increased circulating plasma calcium 4–24 h postinjection. The increase in net calcium transport and increased plasma levels of calcium is consistent with the actions of a hypercalcemic factor. It would appear that the sturgeon rely on calcium for growth and tightly regulate calcium transport. The action in calcium balance is consistent with PTHrP acting as a hypercalcemic factor in sturgeon.

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