Mechanisms of secondary hyperparathyroidism

Silver, Justin; Kilav, Rachel; Naveh-Many, Tally

doi:10.1152/ajprenal.00061.2002

Cited by 145 publications

(107 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Low levels of extracellular Ca stimulate PTH secretion within minutes; while elevated levels of Ca inhibit hormone release and favour the degradation within parathyroid cells (20) . Another major regulator of PTH secretion is 1,25(OH) 2 regulated by 1,25(OH) 2 D 3 (20) .…”

Section: Discussionmentioning

confidence: 99%

Improvement of calcium balance byFructus Ligustri Lucidiextract in mature female rats was associated with the induction of serum parathyroid hormone levels

et al. 2011

View full text Add to dashboard Cite

Fructus Ligustri Lucidi (FLL) is a commonly prescribed herb in many kidney-tonifying Traditional Chinese Medicinal formulae for the treatment of osteoporosis. The present study aimed to identify the active fractions in FLL and to characterise its effects on Ca balance, calciotropic hormone levels as well as bone properties in mature female rats fed diets containing different levels of Ca. In the present study, 4-month-old Sprague -Dawley female rats were treated with either FLL ethanol extract (EE), ethyl acetate-soluble fraction of EE (EAF), water-soluble fraction of EE (WF) or their vehicle for 12 weeks on a medium-Ca diet (MCD, 0·6 % Ca, 0·65 % P). Then, the Sprague -Dawley female rats treated with WF or its vehicle for 12 weeks were fed diets containing different levels of dietary Ca (low-Ca diet (LCD), 0·1 % Ca, 0·65 % P; MCD; high-Ca diet (HCD), 1·2 % Ca, 0·65 % P). The results demonstrated that WF from EE but not EAF exerted a prominent effect on Ca balance by inhibiting urinary and faecal Ca excretion. WF significantly increased Ca balance in rats fed MCD or HCD with an associated increase in serum parathyroid hormone (PTH) levels. WF did not alter bone mineral density or bone mineral content of the tibia in all the rats fed with different levels of dietary Ca. In conclusion, WF was responsible for the positive actions of FLL on Ca absorption and balance. The regulation of Ca balance by WF might involve its action in stimulating PTH production in the mature female rats.

show abstract

Section: Discussionmentioning

confidence: 99%

Improvement of calcium balance byFructus Ligustri Lucidiextract in mature female rats was associated with the induction of serum parathyroid hormone levels

et al. 2011

View full text Add to dashboard Cite

show abstract

“…P deficiency results in a secondary increase in intracellular Ca 2ϩ derived from a decreased efflux of Ca 2ϩ from the cell (45,46). The intracellular Ca 2ϩ might then increase the activity of calcium-responsive pathways, such as cPLA 2 or Ca 2ϩ -calmodulin-dependent protein phosphatases. Our results demonstrate that the PP2B calcineurin is necessary for the regulation of type II Na/Pi gene expression and P transport by low P. The decrease in basal levels of Na/Pi-2 mRNA in the calcineurin A␤ Ϫ/Ϫ mice suggests that calcineurin may also be involved in basal Na/Pi gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…In diseases of phosphorus (P) homeostasis, such as X-linked hypophosphatemia or oncogenic osteomalacia, there is a tremendous renal P loss with severe bone disease (1). In contrast, in chronic renal failure, the P retention leads to secondary hyperparathyroidism with disabling bone disease and vascular calcification associated with a high mortality (2). The kidney has an intrinsic P sensing system that regulates the activity of apical brush border membrane type II Na/Pi co-transporters (3).…”

mentioning

confidence: 99%

Calcineurin Aβ Is Central to the Expression of the Renal Type II Na/Pi Co-transporter Gene and to the Regulation of Renal Phosphate Transport

Moz¹,

Levi²,

Lavi-Moshayoff³

et al. 2004

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Abstract. The sensing and response to extracellular phosphate (Pi) concentration is preserved from prokaryotes to mammals and ensures an adequate supply of Pi in the face of large differences in its availability. In mammals, the kidneys are central to Pi homeostasis. Renal Pi reabsorption is mediated by a Na/Pi co-transporter that is regulated by a renal Pi sensing system and humoral factors. The signal transduction by which Pi regulates type II Na/Pi activity is largely unknown. It is shown that calcineurin inhibitors specifically and dramatically decrease type II Na/Pi gene expression in a proximal tubule cell line and in vivo. Mice with genetic deletion of the calcineurin A␤ gene had a marked decrease in type II Na/Pi mRNA levels and remarkably did not show the expected increase in type II Na/Pi mRNA levels after the challenge of a low-Pi diet. In contrast, the regulation of renal 25(OH)-vitamin D 1␣-hydroxylase gene expression by Pi was intact. This is the first demonstration that calcineurin has a crucial role in the signal transduction pathway regulating renal Pi homeostasis both in vitro and in vivo. These results suggest that the use of calcineurin inhibitors contributes to the renal Pi wasting seen in renal transplant patients.Phosphate (Pi) homeostasis is essential to life and is dependent on active renal reabsorption. In diseases of phosphorus (P) homeostasis, such as X-linked hypophosphatemia or oncogenic osteomalacia, there is a tremendous renal P loss with severe bone disease (1). In contrast, in chronic renal failure, the P retention leads to secondary hyperparathyroidism with disabling bone disease and vascular calcification associated with a high mortality (2). The kidney has an intrinsic P sensing system that regulates the activity of apical brush border membrane type II Na/Pi co-transporters (3). However, it is still not known how the organism senses changes in serum P.There are three mammalian Na/Pi co-transporter families: types I through III. Type II Na/Pi activity is responsible for Ͼ80% of renal P reabsorption and contains three isoforms-IIa through c-of which IIa is the major factor in renal P reabsorption and regulation in adult mice (4). Type II Na/Pi activity is increased by a low serum P and decreased by parathyroid hormone (PTH) and FGF23 (4 -8). The regulation of type II Na/Pi is at the level of recruitment of new transporters to the apical proximal tubule membrane, the level of synthesis of new transporters and their breakdown (5,9). In addition, there is regulation at the level of type II Na/Pi gene expression, which in vivo is mainly posttranscriptional (10,11). In the rat, a cis acting element in the type II Na/Pi co-transporter (Na/Pi-2) mRNA at the junction of the coding region and the 3'-untranslated region (UTR) interacts with trans acting renal cytosolic proteins and determines Na/Pi-2 mRNA stability in response to dietary P restriction (12). An additional level of regulation of Na/Pi-2 is its translational control by a low-P diet (10).The renal type II Na/Pi co-transporte...

show abstract

“…The decrease in functioning renal mass results in hypocalcemia, hyperphosphatemia and reduced calcitriol levels which stimulate parathyroid hormone (PTH) secretion and synthesis and promote parathyroid gland hyperplasia (Silver et al 2002).…”

Section: Introductionmentioning

confidence: 99%

The influence of the progression of secondary hyperparathyroidism on the set point of the parathyroid hormone-calcium curve

Bas

Aguilera–Tejero

Bas³

et al. 2005

Journal of Endocrinology

View full text Add to dashboard Cite

The influence of secondary hyperparathyroidism (2 HPT) on the set point of the parathyroid hormone (PTH)-Ca 2+ curve is controversial. In vitro experiments have shown an increase in the set point. However, clinical studies with hemodialysis patients have provided a variety of results (increases, decreases and no changes in the set point have been reported). The present study was designed to investigate the influence of the progression of 2 HPT on the set point of the PTH-Ca 2+ curve. The PTH-Ca 2+ curve and the expression of parathyroid calcium receptor (CaR mRNA) and vitamin D receptor (VDR mRNA) have been studied in normal rabbits (group I, n=9) and in nephrectomized rabbits (group II, n=18) at two stages after inducing 2 HPT: 2-3 weeks (group IIA) and 5-6 weeks (group IIB). In group I, the set point of the PTH-Ca 2+ curve was 1·63 0·03 mM. A progressive hypocalcemia was detected during the evolution of 2 HPT (groups IIA and IIB). Rabbits from group IIA had a significant (P<0·001) decrease in the set point to values of 1·45 0·02 mM. However, the set point increased significantly in group IIB (P<0·001) to 1·56 0·03 mM. CaR mRNA was similarly decreased in groups IIA (39 12%) and IIB (48 7%). No changes were detected in VDR mRNA. In conclusion, a reduction in the set point of the PTH-Ca 2+ curve in response to decreased extracellular Ca 2+ was detected in the early phases of 2 HPT. However, with the progression of 2 HPT the set point tended to increase even though extracellular Ca 2+ was markedly decreased. The increase in the set point in the course of 2 HPT seems to be a complex process that cannot be fully explained by changes in parathyroid CaR mRNA or VDR mRNA.

show abstract

Mechanisms of secondary hyperparathyroidism

Abstract: Silver, Justin, Rachel Kilav, and Tally Naveh-Many. Mechanisms of secondary hyperparathyroidism. Am J Physiol Renal Physiol 283: F367-F376, 2002; 10.1152/ajprenal.00061.2002

Cited by 145 publications

References 85 publications

Improvement of calcium balance byFructus Ligustri Lucidiextract in mature female rats was associated with the induction of serum parathyroid hormone levels

Improvement of calcium balance byFructus Ligustri Lucidiextract in mature female rats was associated with the induction of serum parathyroid hormone levels

Calcineurin Aβ Is Central to the Expression of the Renal Type II Na/Pi Co-transporter Gene and to the Regulation of Renal Phosphate Transport

The influence of the progression of secondary hyperparathyroidism on the set point of the parathyroid hormone-calcium curve

Contact Info

Product

Resources

About