Regulation of Parathyroid Vitamin D Receptor Expression by Extracellular Calcium

Garfia, B.; Cañadillas, Sagrario; Canalejo, Antonio; Luque, Fernando; Siendones, Emilio; Quesada, Manuel; Almadén, Yolanda; Aguilera–Tejero, Escolástico; Rodríguez, Mariano

doi:10.1097/01.asn.0000037676.54018.cb

Cited by 68 publications

(39 citation statements)

References 26 publications

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“…This result may be explained by that, decreased in serum calcium level lead to stimulation of parathyroid gland to secrete parathormone hormone throgh negative feedback mechanism, under stress. This explanation were in agreement with [20] stated that, parathyroid hormone (PTH) is increased in cold stressed rats . The secretion of PTH is mainly regulated by the extracellular ionized calcium level through a negative feedback mechanism .…”

Section: Discussionsupporting

confidence: 92%

Effect of Sexual Deprivation Stress on Bone of Albino Female Rats

Refaey

Gadalla

Eletreby

et al. 2016

BESPS

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Sexual deprivation stress leads to mental or sexual disorder that can occur after exposure to relative long period of not having sexual relation. Objective: The present work was undertaken to evaluate the possible effects of sexual deprivation on bone remodeling. Materials and Methods: Forty mature adult rats (twenty males and twenty females), of local strains were chosen to be the model of this work , 120-140 gm and aged two months old . They were kept on special formulated diet and tap water was freely allowed. The rats were housed in a wire mesh cage with plastic floor. Each cage was 25 Χ 25 Χ 30 cm . All rats were housed in a laboratory room subjected to normal light dark cycle, All rats were kept for 21 days in the laboratory room at comfortable room temperature for adaption before any experimental interference and to allow a copulation between male and female before deprivation. The whole length of experiment was two months i.e. twelve estrous cycle. The rats were randomly divided into two equal groups, control group, experimental group. Experimental group were exposed to sexual deprivation for 40 days. Vaginal smear examination, was performed approximately at the same time each day over the course of study for detection of acopulatory plug or by observation of spermatozoa in the vaginal smear .Also determination of serum estrogen, progesterone, calcium, phosphorus, parathormone and alkaline phosphatase enzyme in all female rats was done at the end of experiment. Also, morphology of bone and ovary in all female rats were evaluated at the end of experiment. Results: Experimental group showed significant decreased in serum calcium, estrogen and progesterone hormones compared to control group and significant increased in serum parathormone hormone, blood phosphorous level and alkaline phosphatase enzyme compared to control group. As regard histological picture of bone, our results showed that abnormal structure of bone that consisted of discrete cortex and epiphyseal plate (cartilage). Conclusion: The female rats alleged to sexual deprivation may suffer from alteration in the metabolism of bones which may lead to pathological disease called osteoporosis.

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Section: Discussionsupporting

confidence: 92%

Effect of Sexual Deprivation Stress on Bone of Albino Female Rats

Refaey

Gadalla

Eletreby

et al. 2016

BESPS

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“…In normal rats, VDR has been shown to be regulated by extracellular calcium (16) and by calcimimetics (24). To our knowledge, this is the first report of VDR upregulation by calcimimetics in uremic rats.…”

Section: Discussionmentioning

confidence: 65%

Direct upregulation of parathyroid calcium-sensing receptor and vitamin D receptor by calcimimetics in uremic rats

Mendoza¹,

López²,

Canalejo³

et al. 2009

American Journal of Physiology-Renal Physiology

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Tejero E, Rodriguez M. Direct upregulation of parathyroid calciumsensing receptor and vitamin D receptor by calcimimetics in uremic rats. Am J Physiol Renal Physiol 296: F605-F613, 2009. First published December 17, 2008 doi:10.1152/ajprenal.90272.2008.-To investigate whether the effect of the calcimimetic AMG 641 and calcitriol on CaSR and VDR expression could be separated from their ability to reduce parathyroid cell proliferation, five-sixth nephrectomized (5/6 Nx) rats received vehicle, AMG 641, calcitriol, or AMG 641ϩcalcit-riol either daily for 13 days (long-term protocol) or in a single dose (short-term protocol). In the long-term protocol, AMG 641, calcitriol, and their combination significantly reduced the percentage of proliferating parathyroid cells. Proliferation was uncontrolled in the shortterm protocol. A significant increase in CaSR mRNA (% vs. ␤-actin) was detected in rats treated with both calcitriol (1.60 Ϯ 0.30) and AMG 641 (1.66 Ϯ 0.25) for 13 days (P ϭ 0.01 vs. 5/6 Nxϩvehicle, 0.89 Ϯ 0.09); and there was a further increase when both drugs were administered simultaneously (2.46 Ϯ 0.33). In the short-term protocol, only rats receiving AMG 641 alone (2.01 Ϯ 0.33, P Ͻ 0.001) showed increased expression of CaSR mRNA, whereas the combination (1.81 Ϯ 0.20) produced no additional benefit. AMG 641 also increased CaSR mRNA expression in vitro. Changes in VDR mRNA paralleled those of CaSR mRNA. In the long-term treatment, both AMG 641 (0.87 Ϯ 0.14) and calcitriol (0.99 Ϯ 0.12) increased VDR mRNA (P Ͻ 0.05 vs. 5/6 Nxϩvehicle, 0.49 Ϯ 0.10), and the increase was more accentuated when the drugs were combined (1.49 Ϯ 0.45). In the short-term protocol, only treatment with AMG 641, alone (1.52 Ϯ 0.41) or combined with calcitriol (1.86 Ϯ 0.24), increased VDR mRNA. In conclusion, our results demonstrate an acute increase in CaSR mRNA and VDR mRNA in the parathyroid glands of uremic rats treated with AMG 641, in which cell proliferation was uncontrolled, thus supporting a direct effect of calcimimetics on CaSR and VDR expression by hyperplastic parathyroid cells.hyperparathyroidism; PTH; hyperplasia; calcium and calcitriol REGULATION OF MINERAL METABOLISM involves the interaction of multiple organ systems, notably bone and kidneys, and multiple endocrine factors. One such factor is parathyroid hormone (PTH), which, when elevated, is the primary characteristic of secondary hyperparathyroidism (HPT). A predominant feature of secondary HPT is progressive parathyroid gland hyperplasia (12) with concomitantly decreased expression of the calciumsensing receptor (CaSR) (4, 18) and vitamin D receptor (VDR) (15,26). The downregulation of these receptors is an important pathogenic process in the progression of secondary HPT (5,15).

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“…An upregulation of VDR and CaR was also observed in parathyroid glands incubated with a high Ca concentration; these results confirm previous published observations. 12,13 The addition of FGF23 to high Ca did not further increase the expression of parathyroid CaR and VDR. In uremic hyperplastic parathyroid glands, the expression of VDR and CaR is reduced 14 -16 ; the administration of FGF23 to rats with renal failure failed to increase parathyroid ERK1/2 activity and did not have an effect on the expression of VDR or CaR.…”

Section: Discussionmentioning

confidence: 90%

FGF23 Fails to Inhibit Uremic Parathyroid Glands

Canalejo

Martínez-Moreno³

et al. 2010

Journal of the American Society of Nephrology

168

133

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Fibroblast growth factor 23 (FGF23) modulates mineral metabolism by promoting phosphaturia and decreasing the production of 1,25-dihydroxyvitamin D 3 . FGF23 decreases parathyroid hormone (PTH) mRNA and secretion, but despite a marked elevation in FGF23 in uremia, PTH production increases. Here, we investigated the effect of FGF23 on parathyroid function in normal and uremic hyperplastic parathyroid glands in rats. In normal parathyroid glands, FGF23 decreased PTH production, increased expression of both the parathyroid calcium-sensing receptor and the vitamin D receptor, and reduced cell proliferation. Furthermore, FGF23 induced phosphorylation of extracellular signal-regulated kinase 1/2, which mediates the action of FGF23. In contrast, in hyperplastic parathyroid glands, FGF23 did not reduce PTH production, did not affect expression of the calcium-sensing receptor or vitamin D receptor, and did not affect cell proliferation. In addition, FGF23 failed to activate the extracellular signalregulated kinase 1/2-mitogen-activated protein kinase pathway in hyperplastic parathyroid glands. We observed very low expression of the FGF23 receptor 1 and the co-receptor Klotho in uremic hyperplastic parathyroid glands, which may explain the lack of response to FGF23 in this tissue. In conclusion, in hyperparathyroidism secondary to renal failure, the parathyroid cells resist the inhibitory effects of FGF23, perhaps as a result of the low expression of FGF23 receptor 1 and Klotho in this condition. 21: 112521: -113521: , 201021: . doi: 10.1681 Fibroblast growth factor 23 (FGF23) is produced by bone cells and plays a fundamental role in the regulation of mineral metabolism. FGF23 inhibits tubular resorption of phosphate and decreases 1␣ hydroxylase activity, which limits 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] production. Both phosphate excess and high 1,25(OH) 2 D 3 stimulate the production of FGF23. 1 FGF23 signals through a widely expressed receptor (FGFR) that becomes functional only in cells expressing the Klotho protein. 2,3 Klotho, which is expressed in the parathyroid cell, converts FGFR1(IIIc), a canonical receptor for various FGFs, into a specific receptor for FGF23. The tissue-specific unique biological activity of FGF23 is likely to be regulated by the limited local distribution of Klotho. In renal failure, the decrease in glomerular filtration causes phosphate retention, which stimulates the production of FGF23. This elevation in FGF23 levels should help to control phosphate in patients with renal failure. 4 J Am Soc Nephrol

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Regulation of Parathyroid Vitamin D Receptor Expression by Extracellular Calcium

Cited by 68 publications

References 26 publications

Effect of Sexual Deprivation Stress on Bone of Albino Female Rats

Effect of Sexual Deprivation Stress on Bone of Albino Female Rats

Direct upregulation of parathyroid calcium-sensing receptor and vitamin D receptor by calcimimetics in uremic rats

FGF23 Fails to Inhibit Uremic Parathyroid Glands

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