scholarly journals Paracrine Kynurenic Pathway Activation in the Bone of Young Uremic Rats Can Antagonize Anabolic Effects of PTH on Bone Turnover and Strength through the Disruption of PTH-Dependent Molecular Signaling

2021 ◽  
Vol 22 (12) ◽  
pp. 6563
Author(s):  
Krystyna Pawlak ◽  
Beata Sieklucka ◽  
Dariusz Pawlak
Keyword(s):  
Parathyroid Hormone ◽  
Femoral Neck ◽  
Bone Turnover ◽  
Cortical Bone ◽  
Biomechanical Testing ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Tissue Expression ◽  
Femoral Diaphysis ◽  
Molecular Signaling

Secondary hyperparathyroidism and abnormalities in tryptophan (TRP) metabolism are commonly observed in chronic kidney disease (CKD). The present study aimed to establish potential interactions between endogenous parathyroid hormone (PTH) and activation of the bone kynurenine (KYN) pathway in relation to bone turnover and strength in young rats after one month (CKD-1) and three months (CKD-3) of experimental CKD. TRP, KYN, KYN/TRP ratio and bone turnover markers (BTMs) were measured in trabecular and cortical bone tissue. Expression of aryl hydrocarbon receptor (AhR) and the genes involved in osteogenesis was determined in femoral bone. Biomechanical testing of femoral diaphysis and femoral neck was also performed. Activation of the KYN pathway in trabecular bone during CKD development intensified the expression of genes related to osteogenesis, which led to a decrease in cyclic adenosine monophosphate (cAMP) and BTMs levels, resulting in a stiffer and mechanically weaker femoral neck. In contrast, reduction of the KYN pathway in cortical bone allowed to unblock the PTH-dependent anabolic activating transcription factor 4/parathyroid hormone 1 receptor (PTH1R/ATF4) axis, led to cAMP accumulation, better bone turnover and strength in the course of CKD development. In summary, the paracrine KYN pathway in bone can interfere with the anabolic effects of PTH on bone through disrupting PTH-dependent molecular signaling.

Divergent effects of forskolin on 3′,5′ cyclic adenosine monophosphate production and parathyroid hormone secretion

1984 ◽  
Vol 36 (1) ◽  
pp. 87-94 ◽  
Author(s):  
Larry K. Cantley ◽  
Drusilla L. Scott ◽  
Cary W. Cooper ◽  
Darien D. Mahaffee ◽  
George S. Leight ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Hormone Secretion ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate

Lithium administration and phosphate excretion

1976 ◽  
Vol 231 (4) ◽  
pp. 1140-1146 ◽  
Author(s):  
JA Arruda ◽  
JM Richardson ◽  
JA Wolfson ◽  
L Nascimento ◽  
DR Rademacher ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Renal Cortex ◽  
Cyclic Adenosine Monophosphate ◽  
Fractional Excretion ◽  
Adenosine Monophosphate ◽  
Adenyl Cyclase ◽  
Phosphate Excretion ◽  
Camp System

The phosphaturic effect of parathyroid hormone (PTH), cyclic adenosine monophosphate (cAMP), acetazolamide (Az), and HCO3 loading was studied in normal, thyroparathyroidectomized (TPTX), and Li-treated dogs. PTH administration to normal animals markedly increased fractional excretion (F) of PO4 but had a blunted effect on FPO4 in the Li-treated animals. Cyclic AMP likewise markedly increased FPO4 in the normal animals but had a markedly blunted effect in the Li-treated animals. Az led to a significant increase in FNa, FHCO3, and FPO4 in the normal animals. In the Li-treated dogs, Az induced a significant natriuresis and bicarbonaturia but failed to increase phosphaturia. HCO3 loading in normal dogs caused a significant phosphaturia while having little effect on FPO4 in Li-treated dogs. HCO3 loading to TPTX dogs was associated with a lower FPO4 as compared to normal HCO3-loaded animals. These data suggest that Li administration not only blocks the adenyl cyclase-cAMP system in the renal cortex, but it may also interfere with a step distal to the formation of cAMP, since the phosphaturic effect of both PTH and cAMP was markedly diminished in Li-treated animals.

THE CIRCADIAN RHYTHM OF INTACT PARATHYROID HORMONE (1-84) AND NEPHROGENOUS CYCLIC ADENOSINE MONOPHOSPHATE IN NORMAL MEN

1989 ◽  
Vol 121 (1) ◽  
pp. R1-R3 ◽  
Author(s):  
F.C. Logue ◽  
W.D. Fraser ◽  
D.St.J. O'Reilly ◽  
G.H. Beastall
Keyword(s):  
Circadian Rhythm ◽  
Parathyroid Hormone ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Significant Rise ◽  
Optimal Time ◽  
Normal Male ◽  
Intact Parathyroid Hormone ◽  
Normal Men ◽  
Nocturnal Rise

ABSTRACT A pronounced circadian rhythm has been demonstrated for intact parathyroid hormone (1-84) in the serum of normal male adults. The broad nocturnal rise of parathyroid hormone (1-84) secretion appears to be of physiological significance, for it is accompanied by a significant rise in nephrogenous cyclic adenosine monophosphate. The rate of return of parathyroid hormone (1-84) to baseline concentrations varies between individuals, an observation which has implications for the optimal time of sampling for the investigation of possible mild hyperparathyroidism.

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