Retinoic acid suppresses parathyroid hormone (PTH) secretion and PreproPTH mRNA levels in bovine parathyroid cell culture.

MacDonald, Paul N.; Ritter, Cindy; Brown, Alex; Slatopolsky, Eduardo

doi:10.1172/jci117026

Cited by 44 publications

(23 citation statements)

References 33 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the third day of culture, the medium from bovine parathyroid cell monolayers was replaced with defined medium containing either 0.1, 1.0, or 3.0 mM P. The monolayers received fresh medium every 24 h. Cells were lysed at various times with RNAzol (Cinna/Biotecx, Friendswood, TX) and total RNA was isolated and analyzed by Northern blot analysis as described previously (10).…”

Section: Methodsmentioning

confidence: 99%

Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro.

Slatopolsky¹,

Finch²,

Denda³

et al. 1996

J. Clin. Invest.

Self Cite

468

224

View full text Add to dashboard Cite

Dietary phosphorus (P) restriction is known to ameliorate secondary hyperparathyroidism in renal failure patients. In early renal failure, this effect may be mediated by an increase in 1,25-(OH) 2 D 3 , whereas in advanced renal failure, P restriction can act independent of changes in 1,25-(OH) 2 D 3 and serum ionized calcium (ICa). In this study, we examined the effects of dietary P on serum PTH, PTH mRNA, and parathyroid gland (PTG) hyperplasia in uremic rats. Normal and uremic rats were maintained on a low (0.2%) or high (0.8%) P diet for 2 mo. PTG weight and serum PTH were similar in both groups of normal rats and in uremic rats fed the 0.2% P diet. In contrast, there were significant increases in serum PTH (130 Ϯ 25 vs. 35 Ϯ 3.5 pg/ml, P Ͻ 0.01), PTG weight (1.80 Ϯ 0.13 vs. 0.88 Ϯ 0.06 g/gram of body weight, P Ͻ 0.01), and PTG DNA (1.63 Ϯ 0.24 vs. 0.94 Ϯ 0.07 g DNA/gland, P Ͻ 0.01) in the uremic rats fed the 0.8% P diet as compared with uremic rats fed the 0.2% P diet. Serum ICa and 1,25-(OH) 2 D 3 were not altered over this range of dietary P, suggesting a direct effect of P on PTG function. We tested this possibility in organ cultures of rat PTGs. While PTH secretion was acutely (30 min) regulated by medium calcium, the effects of medium P were not evident until 3 h. During a 6-h incubation, PTH accumulation was significantly greater in the 2.8 mM P medium than in the 0.2 mM P medium (1,706 Ϯ 215 vs. 1,033 Ϯ 209 pg/ g DNA, P Ͻ 0.02); the medium ICa was 1.25 mM in both conditions. Medium P did not alter PTH mRNA in this system, but cycloheximide (10 g/ml) abolished the effect of P on PTH secretion. Thus, the effect of P is posttranscriptional, affecting PTH at a translational or posttranslational step. Collectively, these in vivo and in vitro results demonstrate a direct action of P on PTG function that is independent of ICa and 1,25-(OH) 2 D 3 . ( J. Clin. Invest. 1996. 97:2534-2540.)

show abstract

Section: Methodsmentioning

confidence: 99%

Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro.

Slatopolsky¹,

Finch²,

Denda³

et al. 1996

J. Clin. Invest.

Self Cite

468

224

View full text Add to dashboard Cite

show abstract

“…Thus, 9cRA binding to an RXR/ VDR heterodimer may inhibit or promote the vitamin D 3 /VDR effect on genomic transcription rate (Carlberg et al 1993, Schrader et al 1993. It has recently been demonstrated that 9cRA and atRA have similar effects on PTH mRNA expression as vitamin D 3 and thereby suppress PTH release (MacDonald et al 1994, Liu et al 1996. However, this effect may be indirect, since no actual RAR or RXR binding sites seem to be present in the PTH gene promoter region (G Westin, personal communication).…”

Section: +mentioning

confidence: 99%

“…The effect of vitamin D 3 is the rationale for treatment of hyperparathyroidism secondary to uremia with vitamin D 3 in vivo, resulting in lowering of serum PTH levels as well as signs of reduced tumor progression (Slatopolsky et al 1984). In addition, it is evident that parathyroid cells are targets for retinols and retinoic acids, since metabolic conversion of retinol to retinoic acids take place in parathyroid cells, and that these compounds can reduce mRNA levels as well as the release of PTH (MacDonald et al 1994, Liu et al 1996.…”

Section: Introductionmentioning

confidence: 99%

Differentiation of human parathyroid cells in culture

Liu¹,

Ridefelt²,

Åkerström³

et al. 2001

Journal of Endocrinology

View full text Add to dashboard Cite

Continuous culture of parathyroid cells has proven difficult, regardless from which species the cells are derived. In the present study, we have used a defined serum-free low calcium containing medium to culture human parathyroid cells obtained from patients with parathyroid adenomas due to primary hyperparathyroidism. No fibroblast overgrowth occurred, and the human parathyroid chief cells proliferated until confluent. After the first passage the cells ceased to proliferate, but still retained their functional capacity up to 60 days, demonstrated by Ca 2+ -sensitive changes in the release of parathyroid hormone (PTH) and as adequate cytoplasmic calcium ([Ca 2+ ] i ) responses to changes in ambient calcium as measured by microfluorimetry. Low calcium concentrations enhanced, and vitamin D 3 and retinoic acids (RA) dose-dependently inhibited cell proliferation during the first passage, as determined by [ 3 H]thymidine incorporation, immunohistochemistry for proliferating cell nuclear antigen and cell counting. Signs of differentiation were present as the set-points, defined as the external calcium concentration at which half-maximal stimulation of [Ca 2+ ] i (set-point c ), or half-maximal inhibition of PTH release (set-point p ) occur, were higher in not proliferating compared with proliferating cells in P0. Inhibition of cell proliferation was accompanied by signs of left-shifted set-points, indicating a link between proliferation and differentiation.The results demonstrate that human parathyroid chief cells cultured in a defined serum-free medium can be kept viable for a considerable time, and that signs of differentiation occur after proliferation has ceased. The low calcium stimulated cell proliferation may also be inhibited by vitamin D and RA.

show abstract

“…The factors which lead to decreased PTH gene expression in vivo are 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (5) and low phosphate (3). In vitro the action of 1,25-dihydroxyvitamin D3 can be enhanced by retinoic acid (6). The stimuli to PT cell hyperplasia are less well de-fined.…”

Section: Introductionmentioning

confidence: 99%

Parathyroid cell proliferation in normal and chronic renal failure rats. The effects of calcium, phosphate, and vitamin D.

Naveh-Many

Rahamimov²,

Livni³

et al. 1995

J. Clin. Invest.

370

210

View full text Add to dashboard Cite

Secondary hyperparathyroidism is characterized by an increase in parathyroid (PT) cell number, and parathyroid hormone (PTH) synthesis and secretion. It is still unknown as to what stimuli regulate PT cell proliferation and how they do this. We have studied rats with dietary-induced secondary hyper-and hypoparathyroidism, rats given 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and rats after 5/6 nephrectomy for the presence of PT cell proliferation and apoptosis. PT cell proliferation has been measured by staining for proliferating cell nuclear antigen (PCNA) and apoptosis by in situ detection of nuclear DNA fragmentation and correlated with serum biochemistry and PTH mRNA levels. A low calcium diet led to increased levels of PTH mRNA and a 10-fold increase in PT cell proliferation. A low phosphate diet led to decreased levels of PTH mRNA and the complete absence of PT cell proliferation. 1,25(OH)2D3 (25 pmol/d x 3) led to a decrease in PTH mRNA levels and unlike the hypophosphatemic rats there was no decrease in cell proliferation. There were no cells undergoing apoptosis in any of the experimental conditions. The secondary hyperparathyroidism of 5/6 nephrectomized rats was characterized by an increase in PTH mRNA levels and PT cell proliferation which were both markedly decreased by a low phosphate diet. The number of PCNA positive cells was increased by a high phosphate diet. Therefore hypocalcemia, hyperphosphatemia and uremia lead to PT cell proliferation, and hypophosphatemia completely abolishes this effect. Injected 1,25(OH)2D3 had no effect.These findings emphasize the importance of a normal phosphate and calcium in the prevention of PT cell hyperplasia. (J. Clin. Invest. 1995. 96:1786-1793.) Key words: parathyroid hormone * apoptosis* hyperplasia * 1,25(OH)2D3 chronic renal failure.

show abstract

Retinoic acid suppresses parathyroid hormone (PTH) secretion and PreproPTH mRNA levels in bovine parathyroid cell culture.

Cited by 44 publications

References 33 publications

Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro.

Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro.

Differentiation of human parathyroid cells in culture

Parathyroid cell proliferation in normal and chronic renal failure rats. The effects of calcium, phosphate, and vitamin D.

Contact Info

Product

Resources

About