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Thyroparathyroidectomy exaggerates calciuric action of ammonium chloride in rats.

The effects of chronic ammonium chloride (NH4Cl) administration on urinary calcium, urinary hydroxyproline, and calcium and phosphate balances were studied in intact and thyroparathyroidectomized (TPTX) rats. NH4Cl (2 g/100 g diet) was administered for 16 days to growing rats consuming a low calcium (0.1% Ca) diet. NH4Cl increased urinary calcium and hydroxyproline. NH4Cl caused greater urinary calcium loss in TPTX than in intact rats, but hydroxyproline excretion in these groups was similar. Compensatory increases in net alimentary absorption of calcium and phosphate occurred in intact but not in TPTX rats. Urinary cAMP was depressed by thyroparathyroidectomy but was unaffected by NH4Cl. It is concluded that NH4Cl depresses renal tubular reabsorption of calcium and increases bone resorption in the presence and absence of the thyroid and parathyroid glands. However, our results suggest that parathyroid hormone plays an important calcium-sparing role, while calcitonin may act to limit the rate of bone resorption, in intact rats during chronic administration of NH4Cl.

Ammonium Chloride↗

Effect of acute thyroparathyroidectomy on nephron acidification.

The effect of the absence of parathyroid hormone on nephron acidification was determined in rats after acute thyroparathyroidectomy (TPTX). Tubular fluid samples were obtained from the superficial late proximal tubule (LPT), the early distal tubule ( EDT ), and along the inner medullary collecting duct (IMCD), and the results were compared with those obtained from control rats. In the LPT after TPTX, pH was lower, 6.66 +/- 0.01 vs. 6.73 +/- 0.01, and ammonium and net acid delivery were increased significantly. In the EDT no differences in pH, bicarbonate, or net acid were found between groups, whereas ammonium and acid phosphate were significantly different. Along the IMCD in control rats, pH decreased from 6.58 to 5.21 and the addition of about 430 nmol/min of net acid was observed. After TPTX more net acid entered the duct and pH was lower, 5.66, but did not change; neither did the amount of bicarbonate, ammonium, acid phosphate, or net acid change significantly along the duct. Net acid excretion was not different, however, among groups. These results demonstrate that TPTX markedly affects nephron acidification, increasing net acid along the proximal tubule. In contrast to that in control rats, however, net acidification is completed prior to the IMCD. We conclude that the acute absence of parathyroid hormone may significantly affect local nephron acidification but does not alter acid excretion.

Acid-Base Equilibrium↗

Surgical thyroparathyroidectomy of the rabbit.

Previous studies in the rabbit suggest resistance to parathyroid hormone (PTH) despite the reported presence of PTH-sensitive adenylate cyclase activity in renal cortical slices and tubules. The lack of response may reflect difficulties with complete parathyroidectomy in this species, which has been reported to possess 32 accessory glands. Aided by systematic histology of tissues extirpated during exploration, we tested the hypothesis that the rabbit possesses only four functional parathyroid glands and that the rabbit kidney is sensitive to the expected physiological actions of endogenous PTH. In all rabbits studied, only four glands could be identified histologically, two within the thyroids and two located in the fascial plane between the sternohyoid and sternothyroid muscles and the carotid artery. Surgical thyroparathyroidectomy markedly reduced serum Ca (6.3 vs. 10.6 mg/dl in sham-operated controls), increased the clearance (C) (3.51 vs. 0.78 ml/min) and fractional excretion (FE) of Ca (44.5 vs. 8.3%) while decreasing CP (1.14 vs. 2.40 ml/min), FEP (14.8 vs. 29.9%) and adenosine 3',5'-cyclic monophosphate (cAMP) excretion (341 vs. 760 pmol/min). These findings demonstrate the feasibility of using the described techniques for complete parathyroidectomy in the rabbit. Furthermore, they document the presence of only four functioning parathyroid glands and the renal sensitivity to endogenous PTH in this species.

Animals↗

Effect of thyroparathyroidectomy on urinary acidification in diabetic rats.

In previous studies we have shown stimulation of renal acid excretion in the proximal tubules of rats with diabetes of short duration, with no important alterations in glomerular hemodynamics; on the other hand, in thyroparathyroidectomized rats (TPTX model), a significant decrease in renal acid excretion, glomerular filtration rate (GFR) and renal plasma flow (RPF) was detected. Since important changes in the parathyroid hormone-vitamin D-Ca axis are observed in the diabetic state, the present study was undertaken to investigate the renal repercussions of thyroparathyroidectomy in rats previously made diabetic by streptozotocin (45 mg/kg). Four to 6 days after the induction of diabetes (DM), a group of rats were thyroparathyroidectomized (DM + TPTX). Renal functional parameters were evaluated by measuring the inulin and sodium para-aminohippurate clearance on the tenth day. The decrease in the GFR and RPF observed in TPTX was not reversed by diabetes since the same alterations were observed in DM + TPTX. Net acid (NA) excretion was unchanged in DM (6.19 +/- 0.54), decreased in TPTX (3.76 +/- 0.25) and returned to normal levels in DM + TPTX (5.54 +/- 0.72) when compared to the control group (6.34 +/- 0.14 mumol min-1 kg-1). The results suggest that PTH plays an important vasodilator role regarding glomerular hemodynamics, since in its absence the impairment in GFR and RPF was not reversed by the diabetic state. However, with respect to acid excretion, the presence of diabetes was able to overcome the negative stimulus represented by TPTX.

Acidosis, Renal Tubular↗

Effects of magnesium deficiency and thyroparathyroidectomy on calcium active transport by rat duodenum.

Mg deficiency was produced in rats by feeding a Mg-free diet. Ten days of dietary Mg depletion led to an increase in active duodenal Ca absorption in sham-operated animals, but this increase was abolished by thyroparathyroidectomy (TPTX). In addition, TPTX reduced Ca absorption in control aminals fed a Mg-containing diet. More prolonged Mg deficiency was produced by feeding sham-operated animals the Mg-free diet for 19 days. This condition resulted in more marked hypomagnesemia and a depression of Ca transport rates to the level observed in the TPTX groups. These results are consistent with the concept that adaptation of duodenal Ca transport in response to Mg deficiency occurs through an increase in parathyroid hormone (PTH) secretion; however, direct blood PTH measurements will be required to prove this point.

Animals↗

[The effect of thyroparathyroidectomy, parathyroid hormone and calcitonin on plasma strontium in rats].

The effect of thyroparathyroidectomy (TPTX) on the plasmatic Sr concentrations in rats previously supplemented with this element, has been studied, as well as its effect on the treatment of TPTX rats with hormonal combinations and, finally, the one presenting hormonal excess or defect of the phosphocalcium metabolism regulating hormones: parathormone (PTH) and calcitonin (CT). Twenty four hours after TPTX, the plasmatic Sr concentrations show a pattern similar to those of Ca and Mg and contrary to Pi. The subsequent evolution is different, as the plasmatic concentrations increase, probably due to the maintenance of Sr supplementation. The administration of this element to TPTX rats and the treatment with a hormonal combination with two of the following hormones: PTH, CT and T4 antagonize the hormonal effect on the restoration of the plasmatic concentrations of the elements analyzed. The PTH excess and defect (TPTX treated with CT + T4) show plasmatic increases in Sr; the CT excess provokes decreases while the defect (administration of PTH + T4) causes increases. The T4 administration reproduces the CT effects, but inconsistently. These results suggest that CT may be the hormone that plays a regulating role in the plasmatic Sr concentrations.

Animals↗

Thyroparathyroidectomy increases the activity of catalase in the adrenal gland of the rat. A structural and functional study.

At four weeks after thyroparathyroidectomy the activity of catalase in adrenal homogenates was significantly greater (2.95 +/- 0.06 mumoles 0(2)/min/mg protein) than that of controls (2.17 +/- 0.09 mumoles 0(2)/min/mg protein). Increased activity of catalase is related directly to more numerous peroxisomes in cortical cells in the zona fasciculata-zona reticularis of thyroparathyroidectomized rats. The absolute and relative volumes of adrenal gland and zona fasciculata were reduced significantly which is directly correlated with increased peroxisomal activity. A hormonally mediated mechanism reflecting alteration in ACTH, growth hormones and thyroid hormones may mediate adrenocortical atrophy and in turn increase in activity of catalase.

Adrenal Glands↗

Role of serum nonsuppressible insulin-like activity (NSILA) in wound healing. I. Influence of thyroparathyroidectomy on serum NSILA and wound healing in the rat.

Serum contains a 90,000 molecular weight glycoprotein that exhibits insulin-like activity on adipocytes, skeletal muscle, and fibroblasts in tissue culture; however, this protein is physicochemically and immunochemically distinct from insulin and presently is termed "nonsuppressible insulin-like activity ("nsilA)." This study was designed to assess the response of serum NSILA to thyroparathyroidectomy (TPTHX) and to associate this response with tissue repair processes in the injured rat. It was postulated that NSILA modulates the fibroblastic response in wound healing. TPTHX decreased NSILA to 40 percent of control levels (p less than 0.001); 90 male animals subsequently were wounded by either a 10 percent third-degree burn or skin excision. Following injury, NSILA significantly increased in both control and TPTHX groups, but this acute-phase response was attenuated in TPTHX animals. Light microscopy of granulation tissue demonstrated a diminution in the fibroblastic response in TPTHX animals. Hydroxyproline analysis of granulation tissue revealed a significant decrease (p less than 0.025) in collagen content in TPTHX animals with low NSILA levels. The results suggest that serum NSILA levels are controlled, in part, by thyroid hormone and that NSILA may modulate the fibroblastic response of connective tissue repair processes.

Animals↗

Phosphate transport by rat renal brush border membrane vesicles: influence of dietary phosphate, thyroparathyroidectomy, and 1,25-dihydroxyvitamin D3.

In the present work we have investigated whether the changes in the renal handling of inorganic phosphate (Pi) induced by 1) dietary Pi, 2) removal of parathyroid glands and 3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], are associated with alterations in the Na-dependent Pi uptake by brush border membrane vesicles (BBMV) isolated from renal cortex. Sham-operated (SHAM) or thyroparathyroidectomized (TPTX) rats treated or not with 26 pmol/day of 1,25(OH)2D3 i.p. were fed low (0.2%) or high (1.2%) P diet for 7 days. The results showed that in SHAM, TPTX and TPTX+1,25(OH)2D3 the Pi uptake by BBMV was greater after low than high Pi diet. It was greater in TPTX than in SHAM counterparts fed either diets. In TPTX fed low or high Pi diet 1,25(OH)2D3 decreased the Pi uptake to the level observed in SHAM. A striking parallelism was found between variations in Pi uptake by BBMV and in the tubular Pi reabsorption of the whole kidney. The Na-dependent glucose, the mannitol uptake by BBMV, and the alkaline phosphatase activity in cortical homogenates and BBMV were not affected by the various treatments. Thus, dietary Pi, chronic TPTX and 1,25(OH)2D3 appear to specifically affect the Na-dependent Pi transport system bound to the brush border membranes of renal cortical tubules. The alterations observed at this membrane level could account, at least in part, for the changes induced by these factors on the overall tubular reabsorption of Pi.

Animals↗

Chronic thyroparathyroidectomy and tubular handling of phosphate: increased reabsorption in late but not in early proximal tubule.

The fractional reabsorption (FR) of inorganic phosphate (Pi) along the proximal tubule depends upon both the filtered load of Pi (FLPi) and the tubular reabsorptive capacity of the Pi transporting system. To assess the actual effect of parathyroid hormone on the reabsorptive capacity only, the influence of Pi load has to be eliminated. In this study FRPi was determined by free-flow micropuncture along superficial nephrons of chronically (48 h) thyroparathyroidectomized (TPTX) and pair-fed sham-operated (SHAM) rats at identical FLPi [TPTX 3.07 +/- 0.14 (n = 26) and SHAM 3.07 +/- 0.11 (n = 26) mumol/min +/- SEM]. The micropuncture results indicate that in the ranges of tubular fluid over plasma inulin concentration [TF/P)In] 1.00-1.49 and 1.50-1.99, no difference in FRPi between TPTX and SHAM could be detected. It is only between a TF/PIn of 2.0 and 2.49 that chronic TPTX resulted in a significant increase in FRPi. Accordingly the present study indicates that chronic TPTX increases FRPi in late but not in early portions of proximal tubule. Thus in the early proximal tubule the tubular reabsorptive capacity of the Pi transporting system appears to be unaffected by chronic removal of the parathyroid glands. From this result it can be inferred that the increased plasma concentration of Pi which follows the removal of the parathyroid glands, particularly in the chronic stage, will lead to an apparently paradoxical decrease in FRPi in early proximal tubule as a mere consequence of the increased filtered load of Pi.

Absorption↗

Expression of chronic thyroparathyroidectomy on phosphate transport in whole kidney and proximal luminal membranes during phosphate deprivation.

Both parathyroid hormone (PTH) and the dietary supply of inorganic phosphate (Pi) influence the tubular Pi reabsorptive capacity. In this study we have assessed how removal of parathyroid gland affects the response of Pi transport to Pi restriction in the whole kidney and in brush border membrane vesicles (BBMV) isolated from the renal cortex. Intact and thyroparathyroidectomized (TPTX) rats were switched from normal to low Pi diet. The maximal tubular Pi reabsorption per volume of glomerular filtrate (max. TRPi/ml GF) and the initial (3, 6 and 9 s) Na+-dependent Pi uptake by BBMV were determined before and after 1, 2, 3 and 8 days of Pi restriction. The results indicate that before Pi restriction max. TRPi/ml GF was 1.94 +/- 0.04 and 4.03 +/- 0.14 mumol/ml GF in intact and TPTX rats respectively. The corresponding Na+-dependent Pi uptake (3 s value) was 137 +/- 23 in sham and 272 +/- 41 pmol/mg protein in TPTX rats. During Pi restriction the initial difference in max. TRPi/ml GF remained constant throughout the time course study. At 8 days max. TRPi/ml GF was in intact 3.08 +/- 0.09 and in TPTX 5.04 +/- 0.18 mumol/ml GF. In sharp contrast, in BBMV the initial difference between intact and TPTX became completely abolished 8 days after starting the Pi restriction (SHAM = 425 +/- 69; TPTX = 434 +/- pmol/mg protein). In conclusion, the overall tubular Pi transport capacity and the Na+-dependent Pi transport system located in the luminal membrane of the proximal tubule appear to be quite differently affected by changes in the PTH status during Pi restriction.

Animals↗

Effects of thyroparathyroidectomy on the distribution of bromine and iodine in rat tissues.

The concentrations of iodine (I) and bromine (Br) were measured by inductively coupled plasma mass spectrometry in the plasma, kidney, heart, liver, and brain of control and thyroparathyroidectomized (TPTX) rats without and with an additional intake of either NaI or NaBr, 0.5 and 5 mumol/kg/d, respectively, for 21 d. In all groups, the highest concentrations of I and Br were found in the plasma. TPTX did not modify the concentrations of I in tissues, but slightly increased Br in plasma (+33%) and kidney (+24%). The additional intake of I with the drink induced an increase of I concentrations in the tissues tested (from 54 to 191%), except brain, both in control and TPTX rats. This additional intake of I also increased Br levels in the plasma of control (+24%) and TPTX rats (+53%). The additional intake of Br with the drink induced an increase of Br levels in all the tested tissues, brain included (from 85 to 284%). The augmentation was higher in the tissues, particularly brain, of TPTX rats than of controls. The increase of Br in brain after an additional intake contrasts with the absence of increase of I given in the same conditions. This difference between I and Br probably results from the smaller radius of Br ion in comparison with I ion radius. In conclusion, TPTX did not modify the distribution of I in the tested tissues, but slightly increased the concentrations of Br in plasma and kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The regulatory and catalytic subunits of rat liver cyclic AMP-dependent protein kinases respond differently to thyroparathyroidectomy and 1 alpha,25-dihydroxyvitamin D3.

The regulatory subunits of cytoplasmic and nuclear cyclic AMP-dependent protein kinases increased, while the holoenzyme activities fell in the livers of thyroparathyroidectomized (TPTX) rats. 1 alpha,25-dihydroxyvitamin D3 reversed this TPTX-induced decline in holoenzyme activities. TPTX also prevented the increase in holoenzyme activities, but not the increase in the concentration of regulatory subunits that normally occurs in partially hepatectomized animals. An injection of 1 alpha, 25-dihydroxyvitamin D3 into these TPTX animals, at the time of partial hepatectomy restored the increases in holoenzyme activities, without affecting the changes in regulatory subunits. Thus, the synthesis of regulatory and catalytic subunits can be uncoupled by TPTX and 1 alpha, 25-dihydroxyvitamin D3 appears to selectively control the activity of C subunits.

Animals↗

Thyroparathyroidectomy produces a progressive escape deficit in rats.

Abnormal thyroid status and affective disorders have been associated in the human clinical literature. It has recently been shown that pretreatment with thyroid hormone can prevent escape deficits produced by inescapable shock in an animal analogue of depression. In this report we provide evidence that hypothyroid status can produce an escape deficit in rats. While sham-operated rats improved their performance on a simple escape task over three days of testing, thyroparathyroidectomized rats showed a pronounced decrease in their responses. Markov transition analysis was used to obtain conditional probabilities of escaping given a prior escape or failure to escape for the two groups. This analysis shows that the structure of the data set may be similar for the two groups. These results suggest that if intact rats learn to escape, then hypothyroid rats may learn not to escape.

Affect↗

Effects of thyroxine and thyroparathyroidectomy on circadian wheel running in rats.

Thyroparathyroidectomized (TPX) and thyroidectomized male rats display shorter free-running activity periods and enhanced activity levels. These experiments were designed to determine whether this effect is due to the loss of thyroid hormones. The running wheel activity of 36 male rats, 19 TPX and 17 sham operated, was studied. The animals were kept in constant conditions for 7 weeks to obtain baseline data. Half the rats were then injected SC with capsules containing T4, while the other half were injected with blanks. All animals were then allowed to free-run undisturbed for another 8-9 weeks. TPX rats displayed significantly shorter baseline periods (average difference: 0.26 h) and heightened activity. Thyroxine treatment significantly lengthened TPX animals' cycles (average increase: 0.28 h) but did not affect intact rats' circadian rhythms. Thyroxine did, however, significantly decreased the activity levels of both TPX and sham-operated rats. These findings indicate that changes in TPX rats' activity cycles are caused by a reduction in thyroid hormones and that thyroxine acts on activity rhythms and levels by different mechanisms.

Animals↗