Parathyroid gland volume increases with postmaturational aging in the rat

Abstract

To examine the pathophysiology of the age-related rise in the plasma concentration of parathyroid hormone (PTH), we studied the relationships among plasma immunoreactive PTH (iPTH), parathyroid gland volume, parathyroid cell proliferation rate, renal function, and blood Ca 2ϩ in male Fischer 344 rats aged 6-28 mo. Plasma iPTH increased 2.5-fold between 6 and 28 mo and correlated with parathyroid gland volume (r ϭ 0.87). Gland volume began to increase as early as 6-12 mo of age and by 28 mo was threefold greater than at 6 mo. Gland expansion was a consequence of hyperplasia stimulated in part by an increase in cell proliferative activity late in life. Blood Ca 2ϩ and plasma inorganic phosphorus did not change significantly with age. Glomerular filtration rate decreased with age but only after the age of 24 mo. Unlike what has been observed in the human, these data suggest that the age-related increase in plasma iPTH in the rat is linked to parathyroid gland hyperplasia and that early gland growth does not appear to be associated with hypocalcemia or renal insufficiency, but rather to developmentally related metabolic changes. Later in life (Ͼ24 mo), the increase in parathyroid cell proliferation rate, further hyperplastic expansion of the gland, and increase in iPTH secretion appear to be associated with renal insufficiency. parathyroid hormone; renal function; glomerular filtration rate THE SERUM CONCENTRATIONS of immunoreactive (3,9,11,16,23,24,28,31) and bioactive (8) parathyroid hormone (PTH) increase with postmaturational aging in humans and rats. Bone turnover also increases with aging and correlates directly with the rise in circulating PTH, suggesting that the mild hyperparathyroidism of aging may contribute to bone loss in the elderly (6,19). In the Fischer 344 (F344) rat, the serum concentration of PTH begins to increase as early as 12 mo of age, and by 24 mo of age (the mean life span for the F344 rat) is as much as 5 times higher than in 6-mo-old animals (3, 16, 28).In the rat, the age-related increase in serum PTH reflects increased secretion. Fox and Mathew (10) measured the metabolic clearance rate of PTH in 6-and 25-mo-old animals and showed that clearance of PTH does not change with age.The age-related rise in PTH secretion has been interpreted to reflect the decrease in renal function associated with aging (20), decreased intestinal calcium absorption (21), decreased renal conservation of calcium (19), and/or senescent changes intrinsic to the parathyroid secretory cell itself (4,24,27). Whatever the underlying pathology, a consistent feature of the change in PTH secretory dynamics with aging has been an increase in the PTH minimum and maximum secretory rates (9,18,24). Fox (9) reports that minimum and maximum PTH secretion rates are higher in older than in younger animals, and Ledger et al. (18) demonstrated that minimum and maximum serum concentrations of PTH are higher in elderly than in young women. We have shown that the minimum suppressible level of PTH during calcium infusion is two-to th...

Hachimijiogan (Ba-Wei-Di-Huang-Wan), a herbal medicine, improves unbalance of calcium metabolism in aged rats

“…2E) suggests that filtering function of the kidney glomerulus is maintained in our aged rats. This finding is consistent with a previous study showing unchanged Cr clearance in 24-month-old rats that is the same age as used in the present study; however, more aged, i.e., 28-month-old rats showed decreased clearance (Halloran et al, 2002) that is also consistent with human observations (Pattanaungkul et al, 2000). In drug treatment study, although HJG did not affect urinary volume and Cr concentration, it decreased urinary Ca concentration, which led to the result showing that HJG decreased total amount of excreted Ca into urine (Fig.…”

Safety and efficacy of etelcalcetide, an intravenous calcimimetic, for up to 52 weeks in hemodialysis patients with secondary hyperparathyroidism: results of a post-marketing surveillance in Japan

“…The serum cCa levels also tracked slightly lower in younger patients (ESM Fig. 2), which might reflect a relationship between younger age and greater parathyroid gland sensitivity/PTH secretory potential [13][14][15][16], although this has yet to be confirmed in the context of SHPT. As in the prior 52-week study [17], we found no differences in the efficacy and safety of etelcalcetide when patients were divided into subgroups according to their dialysate Ca concentration (Tables 3 and 5).…”

Effects of Calcium Administration on Parathyroid Gland, NaPi 2a Cotransporter and PTH1R in an Animal Model of the Andropause / EFEKTI TRETMANA KALCIJUMOM NA PARATIREOIDNU ŽLEZDU, NAPI 2A KOTRANSPORTER I PTH1R U ANIMALNOM MODELU ANDROPAUZE

“…Due to decreased dietary calcium intake and its diminished absorption from the small intestine in elderly (8), accompanied with an increase in PTH concentration (13), calcium supplementation is widely used for the prevention and treatment of advanced-age osteoporosis (10). In the present study, we investigated the effects of chronic Ca 2+ treatment on the structure and function of PTG, NaPi 2a and PTH1R in the proximal kidney tubules of middle-aged male orchidectomized rats, as an animal model of the andropause.…”

“…The main regulators of synthesis and secretion of PTH are low serum Ca 2+ concentration, mediated through calcium-sensing receptor (CaR) (12), and high serum phosphorus (Pi). Halloran et al (13) established that PTG volume and serum PTH level increase in both rats and humans during ageing. Increased PTH level contributes to bone loss and also induces phosphaturia (14,15), by binding to parathyroid hormone receptor type 1 (PTH1R) in bone tissue and epithelial cells of the kidney proximal tubules.…”