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

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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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 regulates intestinal calcium transport in sea bream (Sparus auratus)

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00892.2005 ◽

2006 ◽

Vol 291 (5) ◽

pp. R1499-R1506 ◽

Cited By ~ 26

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.

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Conflicting actions of parathyroid hormone-related protein and serum calcium as regulators of 25-hydroxyvitamin D(3)-1 alpha-hydroxylase expression in a nude rat model of humoral hypercalcemia of malignancy

Journal of Endocrinology ◽

10.1677/joe.0.1710249 ◽

2001 ◽

Vol 171 (2) ◽

pp. 249-257 ◽

Cited By ~ 13

Author(s):

T Michigami ◽

H Yamato ◽

H Suzuki ◽

Y Nagai-Itagaki ◽

K Sato ◽

...

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Related Protein ◽

Humoral Hypercalcemia Of Malignancy ◽

Vitamin D Metabolism ◽

Hydroxyvitamin D ◽

Humoral Hypercalcemia ◽

Parathyroid Hormone Related Protein ◽

Severe Hypercalcemia ◽

25 Hydroxyvitamin D

In patients with humoral hypercalcemia of malignancy (HHM), serum levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) are generally low, although the pathophysiology of the impaired vitamin D metabolism is not fully understood. In the present study, we have investigated vitamin D metabolism in our newly developed rat model of HHM in which a human infantile fibrosarcoma producing parathyroid hormone-related protein (PTHrP), named OMC-1, was inoculated s.c. into athymic nude rats. In OMC-1-bearing rats, the serum concentration of 1,25(OH)(2)D was markedly reduced when the animals exhibited severe hypercalcemia (Ca > or =15 mg/dl), while it was rather elevated in those with mild hypercalcemia. To further examine whether serum Ca levels affect 1,25(OH)(2)D concentration, we administered bisphosphonate YM529 to OMC-1-bearing rats when they exhibited severe hypercalcemia. The restoration of the serum Ca level by administration of YM529 was accompanied by a marked increase in the 1,25(OH)(2)D level, suggesting that the serum Ca level itself plays an important role in the regulation of the 1,25(OH)(2)D level in these rats. On the other hand, when the OMC-1-bearing rats were treated with a neutralizing antibody against PTHrP, serum 1,25(OH)(2)D levels remained low despite the reduction in serum Ca levels. Expression of 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) in kidney was decreased in OMC-1-bearing rats with severe hypercalcemia, and markedly enhanced after treatment with bisphosphonate. This enhancement in 1 alpha-hydroxylase expression was not observed after treatment with the antibody against PTHrP. These results suggest that PTHrP was responsible for the enhanced expression of 1 alpha-hydroxylase in YM529-treated rats, and that hypercalcemia played a role in reducing the serum 1,25(OH)(2)D level in OMC-1-bearing rats by suppressing the PTHrP-induced expression of the 1 alpha-hydroxylase gene.

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Parathyroid Hormone-Related Protein and Somatolactin in Sea Bream (Sparus aurata) Brain and Pituitary

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1998.tb10800.x ◽

1998 ◽

Vol 839 (1 TRENDS IN COM) ◽

pp. 370-371 ◽

Cited By ~ 2

Author(s):

P.M. INGLETON ◽

D.M. POWER ◽

A.V. M. CANARIO ◽

T.J. MARTIN ◽

J.A. DANKS

Keyword(s):

Parathyroid Hormone ◽

Sparus Aurata ◽

Sea Bream ◽

Related Protein ◽

Parathyroid Hormone Related Protein

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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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The Association of Parathyroid Hormone Related Protein and Vitamin D Level with Serum Calcium Ion in Acute Leukemia Patients

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v26i3.1554 ◽

2020 ◽

Vol 26 (3) ◽

Author(s):

Niniek Wiendayanthi ◽

MI. Diah Pramudianti ◽

Yuwono Hadisuparto

Keyword(s):

Bone Marrow ◽

Vitamin D ◽

Parathyroid Hormone ◽

Acute Leukemia ◽

Serum Calcium ◽

Calcium Ion ◽

Receiver Operating Curve ◽

Related Protein ◽

Parathyroid Hormone Related Protein ◽

D 20

Acute leukemia is bone marrow clonal cell malignancy. One of its complications is hypercalcemia. Parathyroid Hormone-Related Protein (PTHrP) activities involve the regulation of Calcium (Ca) metabolism. Vitamin D is a steroid involved in Ca homeostasis and bone mineralization. This study aimed to analyze PTHrP and vitamin D levels with serum calcium ion in acute leukemia. A cross-sectional study was performed in Clinical Pathology Dr. Moewardi General Hospital Surakarta between July and August 2019, consisting of 41 subjects with new acute leukemia who were diagnosed based on bone marrow puncture and or immunophenotyping result. The cut-off value of Ca ion serum and PTHrP level were determined with a Receiver Operating Curve (ROC). The data were analyzed with a 2x2 table, followed by multivariate logistic regression analysis, and p<0.05 was considered significant. Statistical analysis showed the median age of 25 (2-68) years, 23 (56.10%) ALL, and 18 (43.90%) non-ALL patients. The median of Ca ion and PTHrP were 1.08 (0.84-1.21) mmol/l and 307.52 (20.77-1104.26) pg/mL, respectively. The mean level of vitamin D was 26.45±11.40 ng/mL. Bivariate analysis showed that PTHrP levels ≥ 110.09 pg/mL and vitamin D ≥ 20 ng/mL were related to serum Ca ion ≥ 1.07 mmol/l (PR 4.675; 95% CI: 1.211-18.041; p=0.021 and PR 5.143; 95% CI: 1.279-20.677; p=0.017). Multivariate analysis showed that PTHrP ≥ 110.09 pg/mL and vitamin D ≥ 20 ng/mL were associated with serum Ca ion ≥1.07 mmol/l. There was a significant association between PTHrP, vitamin D level, and serum Ca ion in acute leukemia patients.

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