Regulation of parathyroid hormone secretion by plasma calcium in aging rats

1991 ◽  
Vol 260 (2) ◽  
pp. E220-E225 ◽  
Author(s):  
J. Fox
Keyword(s):  
Parathyroid Hormone ◽  
Hormone Secretion ◽  
Fold Increase ◽  
Male Rats ◽  
Aged Rats ◽  
Adult Rats ◽  
Dihydroxyvitamin D3 ◽  
Set Point ◽  
Skeletal Resistance ◽  
Immunoreactive Parathyroid Hormone

Plasma immunoreactive parathyroid hormone (irPTH) levels increase with aging. This study determined 1) whether NH2-terminal irPTH secretory responses to induced hypocalcemia differ between adult (6-mo-old) and aged (24- to 26-mo-old) male rats and 2) whether a higher set point for irPTH release by Ca is responsible for the elevated irPTH levels with aging. Basal irPTH levels were 68% higher and 1,25-dihydroxyvitamin D3 levels were 44% lower in aged rats. An acutely induced, constant hypocalcemic stimulus [0.32 mM decrement in ionized Ca (Ca2+) for 2 h] was developed in catheterized conscious adult and aged rats by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) infusion using the Ca clamp technique. The initial irPTH secretory response to acute hypocalcemia (5-10 min) was reduced in aged rats (1.9- vs. 3.1-fold increase), suggesting reduced hormone stores. However, higher sustained irPTH levels (30 min to 2 h) were maintained in aged rats, indicating increased irPTH synthesis and release. The EGTA infusion rate necessary to maintain constant hypocalcemia was less in aged rats, suggesting skeletal resistance to PTH. Slow EGTA and Ca infusions were used to determine irPTH secretion at plasma Ca2+ levels from 0.7 to 1.5 mM. In aged rats, irPTH levels were higher at all Ca2+ concentrations, but the set point for irPTH release by Ca2+ was the same as in adult rats. Thus the elevated irPTH secretion in aged rats is not caused by a change in the set point for irPTH release but does result in decreased irPTH stores.

Heterogeneous response to PTH in aging rats: evidence for skeletal PTH resistance

1991 ◽  
Vol 260 (6) ◽  
pp. E933-E937 ◽  
Author(s):  
J. Fox ◽  
M. B. Mathew
Keyword(s):  
Age Groups ◽  
Metabolic Clearance ◽  
Aged Rats ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Dihydroxyvitamin D3 ◽  
Sprague Dawley Rats ◽  
Steady State Levels ◽  
Pth Resistance ◽  
Immunoreactive Parathyroid Hormone

Plasma immunoreactive parathyroid hormone (irPTH) levels increase and renal responsiveness to pharmacological doses of PTH decreases with advancing age. This study tested whether 1) decreased irPTH clearance contributes to the elevated NH2-terminal irPTH levels seen in aged rats and 2) aged rats respond to physiological levels of rat PTH. Conscious adult (7-mo-old) and aged (25-mo-old) male Sprague-Dawley rats were infused for 2 h with rat PTH-(1-34) to achieve steady-state levels in plasma (110-120 pg/ml). Basal irPTH levels were 77% higher (P less than 0.01), and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels were 46% lower (P less than 0.05) in the aged rats. Renal function was not significantly different in these two groups. The metabolic clearance rate of irPTH was rapid and not different in adult and aged rats (99 +/- 8 vs. 111 +/- 7 ml.min-1.kg-1, respectively). After the PTH infusion, plasma ionized and total calcium and 1,25(OH)2D3 levels increased significantly in adult rats, whereas no changes were observed in aged rats. In contrast, a similar significant hypophosphatemic response (23-25% decrease) was seen in both age groups, but the hypophosphatemia was maintained for longer in aged rats. Thus the elevated plasma irPTH levels in aged rats are caused solely by increased secretion. Finally, there is a heterogeneity in the responses to PTH infusion in aged rats, suggesting that the aged rat skeleton, like the kidney, is PTH resistant.

PARATHYROID HORMONE SECRETION IN DISORDERS OF CALCIUM METABOLISM STUDIED BY MEANS OF EDTA

1974 ◽  
Vol 75 (2) ◽  
pp. 286-296 ◽  
Author(s):  
J. H. Lockefeer ◽  
W. H. L. Hackeng ◽  
J. C. Birkenhäger
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Calcium Metabolism ◽  
Hormone Secretion ◽  
Parathyroid Tissue ◽  
Small Mass ◽  
Idiopathic Hypercalciuria ◽  
List Type ◽  
Immunoreactive Parathyroid Hormone ◽  
Pth Level

ABSTRACT In 22 of 28 cases of primary hyperparathyroidism (PHP) the rise in the serum immunoreactive parathyroid hormone (IRPTH or PTH) level observed in response to lowering of the serum calcium by EDTA, exceeded that obtained in 8 control subjects. In 5 of these 22 patients who were studied again after parathyroidectomy the supranormal response was abolished. Fifteen of these 22 hyper-responsive PHP patients had basal IRPTH levels not exceeding the highest level in the controls and that of other groups of patients investigated (idiopathic hypercalciuria, non-parathyroid hypercalcaemia, operated PHP). Fourteen of the 22 hyper-reactive patients with PHP did not show hypocalcaemia during the infusion of EDTA. The extent of the release of PTH elicited by EDTA in cases of PHP does not as yet allow a prediction of the amount of pathological parathyroid tissue present, although all the PHP patients showing a normal release of PTH had a relatively small mass of parathyroid tissue (up to about 1 g) subsequently removed. In 9 cases of nephrolithiasis (8 of whom had idiopathic hypercalciuria) and in 7 cases of non-parathyroid hypercalcaemia, a normal PTH release was found.

REGULATORY HYPERPARATHYROIDISM IN A PIG BREED WITH VITAMIN D DEPENDENCY RICKETS

1979 ◽  
Vol 92 (2) ◽  
pp. 295-308 ◽  
Author(s):  
R. Wilke ◽  
J. Harmeyer ◽  
C. von Grabe ◽  
R. Hehrmann ◽  
R. D. Hesch
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Binding Assay ◽  
Clinical Symptoms ◽  
Plasma Concentrations ◽  
Fold Increase ◽  
Protein Binding Assay ◽  
Deficiency Rickets ◽  
Clinical Healing ◽  
Immunoreactive Parathyroid Hormone

ABSTRACT A radioimmunoassay for porcine parathyroid hormone has been developed and applied to measure immunoreactive parathyroid hormone (PTH) in plasma of pigs with hereditary vitamin D dependency rickets (VDDR) (pseudovitamin D deficiency rickets). Levels of 25-hydroxycholecalciferol (25-(OH)-D3) in plasma were measured by a protein binding assay. Both plasma concentrations of PTH and 25-(OH)-D3 showed an approximately 4-fold increase compared to normal pigs. PTH levels increased with duration of the disease. Daily dosing of the animals with 1–4 μg of 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3) reduced PTH concentrations and resulted in clinical healing. Iv administration of 10 μg of 25-(OH)-D3/day did not alter PTH concentrations nor the clinical symptoms. The results suggest that these animals suffer from regulatory hyperparathyroidism. The metabolic defect could be due to a failure of the kidney to convert 25-(OH)-D3 to 1,25-(OH)2-D3.

Parathyroid, renal, and skeletal responses to induced hypocalcemia in the dog

1982 ◽  
Vol 242 (5) ◽  
pp. E287-E291
Author(s):  
J. Fox ◽  
H. Heath
Keyword(s):  
Parathyroid Hormone ◽  
Urinary Excretion ◽  
Infusion Rate ◽  
Elevated Level ◽  
Fold Increase ◽  
Conscious Dogs ◽  
Clamp Technique ◽  
Very High ◽  
Immunoreactive Parathyroid Hormone

This study was designed to determine 1) whether the plasma immunoreactive parathyroid hormone (IPTH) response to acutely attained, constant (8 h) hypocalcemia is biphasic, and 2) if so, how kidney and bone respond to these changing plasma IPTH levels. We initiated constant hypocalcemia (decrement of Ca, 1.7 mg/dl) in six conscious dogs using the "calcium clamp" technique. Plasma IPTH concentrations increased maximally (fivefold) within 15 min and then decreased gradually over 1 h to a constant, but still elevated level (3.2-fold increase). Urinary excretion of phosphate and hydroxyproline increased more slowly, reaching plateaus at 1.75 h (76% increase) and 5.5 h (70% increase), respectively. The EGTA infusion rate required to maintain constant hypocalcemia was virtually constant (85 +/- 9 mumol.kg-1.h-1) after 20 min and corresponded to skeletal release of about 80 mg Ca.kg-1.day-1. The contribution of the kidney in conserving filtered calcium was relatively minor (2.0 +/- 0.5 mumol.kg-1.h-1). These data demonstrate that the parathyroid response to acute, constant hypocalcemia is biphasic and is temporally divergent from the uniphasic phosphaturic and hydroxyprolinuric responses. The ensuing increased skeletal release of calcium is very high and is maximal within minutes.

Age-related changes of growth hormone secretory mechanisms in the rat pituitary gland

1991 ◽  
Vol 131 (2) ◽  
pp. 251-257 ◽  
Author(s):  
M. Parenti ◽  
D. Cocchi ◽  
G. Ceresoli ◽  
C. Marcozzi ◽  
E. E. Müller
Keyword(s):  
Growth Hormone ◽  
Male Rats ◽  
Lower Percentage ◽  
Aged Rats ◽  
Adult Rats ◽  
Infant Rats ◽  
Age Related ◽  
Rat Pituitary ◽  
Old Rats ◽  
Stimulation Of

ABSTRACT The mechanisms underlying the age-related decrease and increase in somatotroph responsiveness to growth hormone-releasing factor (GHRF) and somatostatin respectively were studied in rat pituitary membranes in vitro. Basal adenylate cyclase (AC) activity was similar in pituitary membranes from rats of 8 days (either sex) and male rats of 3 months, but it was almost threefold higher in membranes from male rats of 21–23 months. GHRF induced a lower percentage stimulation of AC activity in membranes from infant and old than adult rats. Somatostatin inhibited stimulation of AC induced by forskolin more effectively in membranes from adult than infant and old rats. In parallel experiments, since the tissue we used is formed by a mixed population of pituitary cells, we evaluated, for comparison, the effect on AC of neurohormones, i.e. vasoactive intestinal polypeptide (VIP) and dopamine which act primarily on lactotrophs. VIP induced a lower fold-stimulation of AC activity in membranes from infant and old than adult rats. Dopamine inhibited forskolin-induced stimulation of AC in the following rank order of magnitude: old, adult and infant rats, and was also more effective in inhibiting basal AC activity in old than in adult rats. The stimulatory and inhibitory G proteins (Gs and Gi) coupled to AC were measured indirectly by evaluating stimulatory and inhibitory effects of different concentrations of GTP on AC. GTP, at stimulatory concentrations, increased AC activity in membranes from infant and adult rats similarly whereas its effect was significantly greater in membranes from old rats. Conversely, GTP, at inhibitory concentrations, decreased AC activity similarly in membranes from adult and infant rats, whereas in old rats inhibition was apparent at more than a tenfold lower concentration of GTP. These data suggest (1) that the greater somatotroph sensitivity to GHRF in terms of GH secretion of the early postnatal period is not due to supersensitive GHRF receptors but rather may be accounted for, at least partially, by the low function of somatostatinergic receptors; (2) that the inability of GHRF to stimulate GH release in aged rats probably results from an uncoupling between the GHRF receptor and the G protein; and (3) that in aged rats the decreased ability of somatostatin to inhibit AC activity, in spite of the high Gi activity, results from a reduced number of somatotroph cells and, hence, receptors. Journal of Endocrinology (1991) 131, 251–257

THE EFFECT OF CALCIUM AND DIBUTYRYL-cAMP ON THE SECRETION OF PARATHYROID HORMONE BY HUMAN PARATHYROID ADENOMAS IN ORGAN CULTURE

1977 ◽  
Vol 85 (3) ◽  
pp. 541-547 ◽  
Author(s):  
M. Dietel ◽  
G. Dorn ◽  
R. Montz ◽  
E. Altenähr
Keyword(s):  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Organ Culture ◽  
Inverse Relationship ◽  
Calcium Concentration ◽  
Culture Medium ◽  
Hormone Secretion ◽  
Dibutyryl Camp ◽  
Parathyroid Adenomas ◽  
Immunoreactive Parathyroid Hormone

ABSTRACT The effect of different calcium concentrations as well as dibutyryl-cyclic adenosine 3′,5′-monophosphate (DB-cAMP) on the secretion of parathyroid hormone by human parathyroid adenomas taken from patients with primary hyperparathyroidism (pHPT) was studied in organ culture. Their influence on the release of hormone was determined. The tissue was incubated in culture medium for 4 h; the medium was changed hourly and analyzed for immunoreactive parathyroid hormone (PTH) by radioimmunoassay. The hormone secretion showed an inverse relationship to different calcium concentrations in the medium and could be stimulated independently of the calcium concentration by adding DB-cAMP. These results suggest that the examined parathyroid adenomas are sensitive to physiological stimuli.

scholarly journals Toxicity Evaluation of the Subacute Diazinon in Aged Male Rats: Hematological Aspects

2020 ◽  
Vol 20 (3) ◽  
pp. 198-201
Author(s):  
Saeed Samarghandian ◽  
Tahereh Farkhondeh ◽  
Shahnaz Yousefizadeh
Keyword(s):  
Matched Control ◽  
Male Rats ◽  
Mean Corpuscular Hemoglobin ◽  
Aged Rats ◽  
Toxicity Evaluation ◽  
Corpuscular Hemoglobin ◽  
Adult Rats ◽  
Age Dependent ◽  
Controversial Topic ◽  
Hematological Alterations

Background & Objective:: Age-dependent Organophosphates (OPs) toxicity is a controversial topic. The present study was designed to investigate the effect of the sub-acute exposure to diazinon (DZN), one of the main OPs insecticides, on the hematological alterations in adult and aged male rats. Methods: For the aim of this approach, the adult and aged rats were administered with DZN (15 mg/kg, orally) for 4 weeks. Then, the blood samples were collected from the retro-orbital sinus for measuring red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), platelets (PLT), MCV (mean corpuscular volume), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin (MCHC). Results: The obtained results indicated that DZN significantly decreased RBCs (4.93 ± 0.41), Htc (28.12 ± 1.21), Hb (10.31 ± 0.36), MCHC (30.51 ± 2.04), MCV (62.86 ± 2.58), and PLT (265.6 ± 34.81) values in the adult and aged rats versus the age-matched control rats. Moreover, RBC, Hb, and Htc levels decreased significantly in the aged rats versus adult rats. However, no significant differences were observed between MCHC, MCV, and PLT levels in adult and aged rats. Moreover, the MCH concentration did not change in any group. Additionally, DZN did not deteriorate the hematological alterations in the aged rats versus adult rats. Conclusion: The present study showed that the toxicity of DZN is not associated with age. However, more studies should be conducted to confirm this finding.

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