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S U Toverud

Publications and source records attributed to S U Toverud.

At least 19 recordsLinked to original sources

Several anesthetics, but not diethyl ether, cause marked elevation of serum parathyroid hormone concentration in rats.

The effects of anesthetics on serum parathyroid hormone (PTH) concentrations were determined by a new homologous two-site immunoradiometric assay for rat PTH. Serum PTH concentrations (mean +/- SE) from ether-anesthetized rats (14.7 +/- 1.5 pg/ml, n = 22) were not significantly different from those of decapitated unanesthetized female rats (13.0 +/- 1.8 pg/ml, n = 21). Serum PTH concentrations in pg/ml (n = 4-14) for other anesthetics tested were: ketamine, 12.5 +/- 1.1; Na pentobarbital, 23.3 +/- 2.4; methoxyflurane (inhalation), 42.2 +/- 6.8; and xylazine combined with ketamine, 51.4 +/- 11.3 pg/ml. The latter two concentrations were significantly (p < 0.001) higher than the values for all other anesthetics and decapitation. Elevation of serum PTH induced by pentobarbital or ketamine + xylazine increased with time under anesthesia. Neither serum Ca2+ concentrations nor pH differed among any of the groups. We conclude that anesthesia induced by pentobarbital, methoxyflurane, or ketamine + xylazine in rats leads to a marked elevation of serum PTH levels that appears to be related to the duration of anesthesia and not due to any measurable fall in serum Ca2+.

Anesthetics

Suppression of circulating calcitriol and duodenal active Ca transport by ketoconazole in pregnant rats.

Active Ca transport in the duodenum and the circulating level of calcitriol are elevated during pregnancy and lactation in the rat. Because calcitriol stimulates Ca transport in nonmated rats, we investigated its contribution to the increased transport during pregnancy and lactation. Rapid suppression of calcitriol from 28 +/- 3 to 8 +/- 0.4 pg/ml with the steroid hydroxylase inhibitor ketoconazole resulted in a 34% suppression of Ca transport in nonmated rats. At the end of pregnancy, when calcitriol concentration was suppressed from 64 +/- 7 to 12 +/- 2 pg/ml, the transport ratio decreased by 44%. Ca transport did not correlate with calcitriol levels between 40 and 80 pg/ml, suggesting a threshold level for maximal Ca transport stimulation. During lactation at even higher calcitriol levels, ketoconazole treatment again resulted in marked reduction in calcitriol from 124 +/- 1 to 71 +/- 12 pg/ml, but without any concurrent reduction in Ca transport in the duodenum. We conclude that in the vitamin D-replete rat the pregnancy-mediated, and probably also the lactation-mediated, increase in active Ca transport capacity is dependent on an increase in circulating calcitriol up to a certain threshold level.

Animals

Determination of bioactive rat parathyroid hormone (PTH) concentrations in vivo and in vitro by a 2-site homologous immunoradiometric assay.

A new homologous 2-site assay for rat parathyroid hormone (IRMA), developed by Immutopics, Inc., has been evaluated and compared with a bone cell cAMP bioassay. Circulating PTH for adult rats assayed with this IRMA are in the range 10-15 pg/ml, and of the same order of magnitude as published values for biologically active PTH. The standard curve for the IRMA was linear over the range 3.4-240 pg/ml of rPTH 1-34, and serum samples diluted in parallel with the standard curve. The within-assay and between-assay coefficients of variation ranged from 5.2% (n = 18) to 7.6% (n = 24) and 8.3% (n = 16) to 26.4% (n = 10), respectively. Serum PTH values (mean +/- S.E.) for parathyroidectomized rats were 3.5 +/- 0.6 pg/ml (n = 18) versus 10.3 +/- 1.4 pg/ml (n = 16) for intact non-mated rats. Calcium injections suppressed circulating PTH by 50%. Lactating rats had serum PTH levels 5-fold higher and vitamin D deficient rats 60-fold higher than non-mated controls. PTH secreted from parathyroid cells in vitro was in the range 60-490 pg/ml as determined by the IRMA. These values represented 86.0 +/- 9.0% of the comparable bioassay values, indicating that the IRMA detects only bioactive PTH.

Animals

Parathyroidectomy abolishes the increase of renal 25-hydroxyvitamin D-1 alpha-hydroxylase in lactating rats.

Serum ionized calcium (Ca), but not inorganic phosphorus or immunoreactive parathyroid hormone, negatively correlates with renal 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) and serum 1,25-dihydroxyvitamin D in intact lactating rats. The present study tested the hypothesis that the presumed stimulation of renal 1 alpha-hydroxylase by hypocalcemia requires the presence of intact parathyroid glands. Lactating and nonlactating rats were surgically parathyroidectomized (PTX) or sham-operated (sham) at 9-10 days of lactation. Later (24 h) the rats were bled, nephrectomized, and killed. In lactating PTX rats, serum ionized Ca decreased to 50% of the level of sham rats, and serum 1,25-dihydroxyvitamin D fell to 37 +/- 5.0 pg/ml compared with 82 +/- 13.0 pg/ml for sham lactating rats but was still 2.5 times the value for nonlactating PTX rats (15 +/- 0.8 pg/ml). In contrast to the still elevated serum 1,25-dihydroxyvitamin D concentration in lactating PTX rats, renal 1 alpha-hydroxylase was suppressed to the same low level as in nonlactating PTX rats, suggesting the existence of extrarenal synthesis of 1,25-dihydroxyvitamin D in lactation. A curvilinear relationship was revealed between serum ionized Ca and renal 1 alpha-hydroxylase in sham lactating and nonlactating rats (r2 = 0.71, P < 0.0001). However, in PTX rats, decreasing ionized Ca did not lead to any increase in 1 alpha-hydroxylase above the low baseline values seen at ionized Ca concentrations between 1.3 and 1.5 mM. We therefore conclude that intact parathyroid glands are required for hypocalcemia to activate renal 1 alpha-hydroxylase in female rats.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase

Decreased heterotopic osteogenesis in vitamin-D-deficient, but normocalcemic guinea pigs.

The effect of vitamin D deficiency unhampered by hypocalcemia on de novo bone formation was studied in guinea pigs. Heterotopic induction of osteogenesis was evaluated 4 weeks after intramuscular transplantation of allogenic urinary bladder transitional epithelium from vitamin-D-repleted (+D) donors into +D and -D recipients. In -D recipients the frequency of osteogenesis and the amount of induced bone were significantly diminished; induced bone was less mature, scantly cellular woven bone poorly repopulated with bone marrow. No effect of vitamin D deficiency on orthotopic bone growth and on mineralization of orthotopic and heterotopically induced bone was observed. It is proposed that in addition to inducing factors (BMPs, growth factors) which may be responsible for transformation of mesenchymal cells to osteoprogenitor cells, normal concentrations of 1,25-(OH)2D3 may be required for proliferation and further differentiation of these cells into osteoblasts and for expression of genes engaged in extracellular matrix formation and maturation.

Alkaline Phosphatase

Intensity of lactation modulates renal 1 alpha-hydroxylase and serum 1,25(OH)2D in rats.

Renal 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity and serum 1,25-dihydroxyvitamin D [1,25(OH)2D] concentration were measured in lactating rats suckling litters of 3, 6, or 12 pups to determine the effect of increasing lactational intensity on the biosynthesis of 1,25(OH)2D. Serum Ca2+, total Ca, Pi, and immunoreactive parathyroid hormone were also determined. The average daily litter weight gain for each litter size was calculated from the gain over the last 4-6 days of each of three experiments and was used as an index of lactational intensity. Highly significant correlation coefficients were found between 1 alpha-hydroxylase and average daily litter weight gain (rs = 0.63, n = 53, P less than 0.001), serum 1,25(OH)2D and average daily litter weight gain (rs = 0.62, n = 50, P less than 0.001), 1 alpha-hydroxylase and serum total Ca (rs = -0.52, n = 53, P less than 0.001), and average daily litter weight gain and total Ca (rs = -0.52, n = 53, P less than 0.001). Neither serum phosphorus nor immunoreactive parathyroid hormone correlated significantly with 1 alpha-hydroxylase. In addition, construction of regression models using a stepwise forward variable selection procedure revealed serum total Ca concentration to be a significant predictor for both serum 1,25(OH)2D and renal 1 alpha-hydroxylase in lactating rats. These data support the hypothesis that increasing lactational intensity leads to decreasing serum Ca concentration, resulting in stimulation of 1 alpha-hydroxylase activity and a rise in the serum 1,25(OH)2D level.(ABSTRACT TRUNCATED AT 250 WORDS)

25-Hydroxyvitamin D3 1-alpha-Hydroxylase

Pregnancy- and lactation-induced changes in active intestinal calcium transport in rats.

A time course study of active Ca transport in the duodenum and the terminal ileum was conducted using the everted gut sac technique during the last week of pregnancy and throughout lactation. A triphasic pattern was revealed in the proximal duodenum: a marked rise between 18 and 20 days of pregnancy, a plateau maintained during the last 3 days of pregnancy and the first 2-3 days of lactation, and a fall by day 4 of lactation. The late-pregnancy rise was significant also when expressed as milligrams Ca transported relative to tissue weight, indicating that intestinal hypertrophy was not the cause of the increase. The ratio of serosal to mucosal Ca concentration remained low until approximately day 11 of lactation, when it rose toward a new peak. There was no active Ca transport in the ileum until the third week of lactation. Serum prolactin levels increased 10-fold between 18 and 20 days of pregnancy and remained high until at least day 7 of lactation, but did not correlate significantly with duodenal Ca transport. Injected rat prolactin did not result in a precocious rise in Ca transport in pregnant rats. The fluctuations in duodenal Ca transport during lactation were reflected by a small, but statistically significant, decrease in net fractional Ca absorption at 6-9 days compared with either 2-4 days or 13-16 days. We suggest that duodenal active Ca transport plays only a small role in total intestinal Ca absorption in the lactating rat except when dietary Ca is greatly restricted.

Absorption

Parathyroid hormone is not required for normal milk composition or secretion or lactation-associated bone loss in normocalcemic rats.

To determine if parathyroid hormone (PTH) is essential for lactation in rats, the parathyroid glands were removed surgically during the first week of lactation and the rats were given a diet containing a high calcium-phosphorus ratio to maintain a normal serum calcium concentration. Lactating rats were placed on diet containing 1.2% calcium (Ca) and 0.8, 0.6, or 0.4% phosphorus (P) on day 2 postpartum (PP) and were parathyroidectomized (PTX) at 4-6 days PP. At 10 days PP serum Ca was 10.5 +/- 0.2 mg/dl (mean +/- SEM) for PTX rats and 10.4 +/- 0.3 mg/dl in sham-operated lactating rats when the diet contained 0.6% P. When the diet P was 0.8%, the litters gained little or no weight and serum Ca fell to 6.9 +/- 0.6 mg/dl by day 10 PP in PTX rats compared with 10.2 +/- 0.2 mg/dl in sham rats. PTX rats fed the diet containing 1.2% Ca and 0.6% P maintained a normal serum Ca level until at least day 18 PP, but their serum P levels fell gradually from approximately 5 mg/dl at 10 days to 3 mg/dl at 18 days PP. In spite of this hypophosphatemia, the litters of PTX and sham rats had gained the same amount of weight by age 16 days, indicating equal milk production in the two groups. Milk Ca, P, and total solids were not significantly different between PTX and sham rats on day 11 PP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The ovariectomized, lactating rat as an experimental model for osteopenia: calcium metabolism and bone changes.

The ovariectomized, lactating rat (Sprague-Dawley) is proposed as an experimental model for the rapid development of osteopenia which may be used to test the effectiveness of bone-retentive drugs potentially useful in treating osteoporotic women. Rats were ovariectomized (OVX) on day 2 postpartum and were kept on a low-calcium diet (0.1%). Measurements of serum total calcium, ionic calcium, albumin and parathyroid hormone were conducted between days 4 and 21 of lactation. Serum total and ionic calcium and albumin were significantly lower and serum parathyroid hormone was significantly higher in all lactating rats at 16 days postpartum compared to nonlactating controls. Mean bone mass of the femurs of OVX lactating rats measured at day 21 was approximately 50% of that of non-lactating intact controls. The enhanced duodenal calcium absorption (in everted gut sacs) associated with lactation was not affected by OVX and neither was the average litter weight gain between 2 and 14 days of lactation. In conclusion, lactation coupled with a low-calcium diet resulted in marked osteopenia, depressed serum calcium (both total and ionic) and significantly elevated serum parathyroid hormone concentration. The rapid and extensive bone loss of this model makes it appropriate for the study of therapeutic agents designed to retain bone mass.

Animals

Regulation of serum 1,25-dihydroxyvitamin D3 in lactating rats.

To characterize further the mechanism(s) underlying the increased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] concentration associated with lactation in the rat, we examined hormone biosynthesis [i.e., renal 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity] and hormone disappearance in groups of lactating Holtzman rats and age- and sex-matched nonlactating controls. 1 alpha-Hydroxylase activity was significantly greater in kidneys from lactating rats (4.0 +/- 0.42 fmol.mg-1.min-1) on a basal diet than in those from nonmated females (1.4 +/- 0.08 fmol.mg-1.min-1), an increment sufficient to account for the observed fourfold elevation of 1,25(OH)2D3 in the dams. The increase occurs despite the lower serum 1,25(OH)2D3 levels in lactating than in nonlactating rats at 12 and 24 h after a bolus injection of 1,25(OH)2D3 (2 ng/g body wt). Elevation of serum 1,25(OH)2D3 is not a requisite consequence of lactation, however, because dams receiving supplemental calcium from food (1.6%) and water (0.3%) exhibited no increase of either serum 1,25(OH)2D3 or 1 alpha-hydroxylase activity compared with controls. In contrast, lactating rats that received a diet with only 0.1% calcium had 5-fold higher serum 1,25(OH)2D3 levels and 20-fold higher 1 alpha-hydroxylase activity than nonlactating rats on the same diet. We conclude that other factors in conjunction with lactation, but not the lactating state per se, promote the changes in 1,25(OH)2D3 metabolism observed.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase

Ultrastructural localization of tartrate-resistant, purple acid phosphatase in rat osteoclasts by histochemistry and immunocytochemistry.

The intracellular localization of the tartrate-resistant purple acid phosphatase in osteoclasts of developing rat bone has been determined immunocytochemically using an antiserum to the purified bone-derived purple acid phosphatase. The localization of the immunoreactivity was compared with the results of enzyme histochemistry using p-nitrophenylphosphate as substrate and 10 mM tartrate. Both methods revealed the presence of the enzyme in numerous vesicles of various sizes up to 2-3 microns in diameter and in granules. There was no immunoreactivity in the Golgi apparatus, and tartrate completely inhibited the histochemical activity of this organelle. No consistent extracellular activity could be detected, nor was any reaction product observed at the ruffled border. The localization of the tartrate-resistant purple acid phosphatase in osteoclasts is consistent with an intracellular function for this enzyme.

Acid Phosphatase

Hypercalcemia fails to suppress elevated serum parathyroid hormone concentrations during lactation in rats.

We have previously reported that increased serum immunoreactive parathyroid hormone (iPTH) in the lactating (L) rat is generally accompanied by hypocalcemia when diets containing 0.4% calcium (Ca) or less are fed. However, instances were also observed in which elevated iPTH levels did not coincide with a hypocalcemic signal. To test the hypothesis that iPTH levels can remain elevated even in the presence of hypercalcemia in lactation, a diet containing 1.2% Ca and 0.4% phosphorus (P) was fed to lactating rats in three experiments (A, B, and C) to achieve serum ionized calcium (ICa) levels approximately 10% above levels for nonmated (NM) controls. The serum ICa of NM controls fed the 1.2% Ca diet was slightly, but significantly, elevated, and serum iPTH (determined by an N-terminal specific assay) was significantly suppressed compared with NM controls fed a 0.4% Ca diet. In experiment A, L rats fed a 1.2% Ca diet had 81% higher serum iPTH levels than NM controls fed the same diet in spite of a mean (+/- SEM) ICa level of 1.77 +/- 0.05 mM for L rats versus 1.46 +/- 0.01 mM for NM controls; NM controls fed a 0.4% Ca diet had serum ICa of 1.37 +/- 0.01 mM. This novel finding of significantly higher iPTH and ICa in L compared with NM rats fed a 1.2% Ca and 0.4% P diet was confirmed in experiment B with eight rats in each group of L or NM rats fed either the 1.2% or the 0.4% Ca diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Adverse effects of a high-glucose diet on body weight and plasma calcium and 1,25-dihydroxyvitamin D3 levels in calcium-deficient growing rats.

We tested the hypothesis that dietary calcium would lead to greater impairment of body weight gain and calcium homeostasis if rats are fed a diet with a high glucose content compared with our standard diet in which the carbohydrate is supplied by whole wheat flour. Groups of female rats at 21 days of age were given either of two equivalent calcium-deficient diets with carbohydrate supplied either by glucose (LCaG) or by wheat flour (LCaW). Control rats were fed the wheat-flour diet containing 0.4% calcium. Since previous studies indicated divergent effects of glucose-based and flour-based diets on body weight in vitamin D-deficient rats, we designed a parallel study with vitamin D-deprived rats. Compared with rats fed the LCaW diet, the rats fed the LCaG diet had inferior body weight gain and more severe hypocalcemia (1-2 mg/ml lower) over a 40-day period, and no significant elevation of the plasma 1,25(OH)2D3 level at 61 days of age. Rats fed the LCaW diet maintained a 3-fold elevation of plasma 1,25(OH)2D3 relative to the level of control rats fed the 0.4% calcium diet. The dry weight and percent ash of tibias were similarly reduced in the two calcium-restricted groups compared to the control group. Among the vitamin D-deprived rats, those fed the glucose diet had poorer weight gain than those fed the wheat flour diet. However, both groups had similarly depressed serum calcium level, tibia ash content and 1,25(OH)2D3 level. Thus, a glucose diet combined with calcium restriction or vitamin D deprivation appears to accentuate the impairment of body weight gain and, when combined with calcium restriction, it also accentuates the impairment of calcium homeostasis and interferes with the adaptive increase in plasma 1,25(OH)2D3.

Animals

Modulation of serum parathyroid hormone and ionized calcium concentrations during reproduction in rats fed a low calcium diet.

Moderate dietary restriction of calcium (0.1% Ca) was used to accentuate the changes in serum immunoreactive parathyroid hormone (iPTH) that had been reported earlier in lactating rats fed 0.4% Ca diet. In addition, the effects of this low-Ca diet on serum total and ionized Ca and iPTH during pregnancy, extended lactation, and weaning were examined. The positive correlation between serum total and ionized Ca was highly significant (r = 0.88, p less than 0.001, n = 120). Serum iPTH was significantly higher (36%) in pregnant rats on the day of parturition compared to nonmated controls, and there was a concomitant decrease in both total and ionized serum Ca. Within 1 day after parturition, however, serum Ca had risen to the control level. Serum iPTH remained significantly elevated during the first 2 weeks of lactation, and increased further during the third week of lactation to a level more than twice that of nonlactating controls. Serum Ca fell gradually during the second week of lactation. The high serum iPTH levels were maintained for another 2 weeks when lactation was extended with foster litters. Within 6 hr of removal of the suckling pups on day 16 of lactation, maternal serum ionized and total Ca had risen and serum iPTH had fallen; all three parameters were at levels similar to those of nonmated controls by 24-48 hr after weaning. The data suggest that serum ionized Ca is a major factor contributing to the hyperparathyroid state during lactation in rats fed a low-Ca diet.

Aging

Increase in serum parathyroid hormone concentration in the lactating rat: effects of dietary calcium and lactational intensity.

The change in circulating levels of immunoreactive parathyroid hormone (iPTH), measured with an N-terminal specific radioimmunoassay, was examined during lactation in rats. In lactating rats consuming a diet containing 0.4% Ca (basic diet), serum iPTH was a) increased by an average of 53% between days 10 and 18 compared to the level of age-matched nonlactating rats (24.7 +/- 2.1 pg/ml vs 16.1 +/- 0.8 pg/ml, mean +/- SE, p less than 0.01) and b) significantly higher in dams suckling large litters (10-15 pups) than in dams suckling small litters (3 pups) over the period 3-13 days of lactation. Lactating rats consuming a low calcium diet (0.04% Ca), had serum iPTH levels on days 16-18 of lactation approximately twice those of nonlactating rats fed the same diet and 73% higher than those of lactating rats fed the basic diet. Serum Ca concentrations were 22% and 10% lower in dams consuming the 0.04 and 0.4% Ca diets, respectively, than in the nonlactating controls fed the same diets. Regression analysis showed a significant (p less than 0.001) negative correlation between iPTH and total serum calcium. Compared with nonmated controls, net mineral loss from femurs of dams consuming the 0.4% Ca diet was a) insignificant at day 6, b) 27% at day 15, and c) 34% at day 21 of lactation. Our data demonstrate that lactation in the rat is characterized by hyperparathyroidism that appears to be related to lactational intensity and that is accentuated when dietary calcium intake is restricted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Regulation by dietary calcium of vitamin D-dependent calcium-binding protein and active calcium transport in the small intestine of lactating rats.

To test the hypothesis that vitamin D-dependent calcium-binding protein (CaBP) and active calcium (Ca) transport in the small intestine of vitamin D-replete lactating rats are regulated by dietary Ca intake, pregnant rats were given a high Ca (1.6% Ca and 1.4% phosphorus) or low Ca (0.1% Ca and 0.4% phosphorus) diet starting 3 days before delivery. Toward the end of lactation (days 16-23) the rats were killed, and active Ca transport (using everted gut sacs) and CaBP were determined in duodenum, jejunum, and ileum. The right tibiae were used for bone weight and ash determinations. The Ca transport ratios and CaBP concentrations in jejunum and ileum were significantly increased only in the low Ca group. In contrast, in the duodenum both parameters were equally high regardless of the diet. Nonlactating rats given the two diets for the same length of time had the expected increase in both parameters in the duodenum when fed the low Ca diet. Nonlactating rats, in contrast to lactating rats, had undetectable CaBP in jejunum and ileum regardless of diet. Lactating rats fed the high Ca diet had no net loss of bone at the end of lactation compared with rats on day 1 of lactation. In contrast, lactating rats fed the low Ca diet had a net loss of 44% of bone weight. Plasma 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] concentrations on the 21st day of lactation were (mean +/- SE) 538 +/- 96 and 46 +/- 18 pg/ml in rats consuming the low and high Ca diets, respectively. The comparable values for the nonlactating rats were 140 +/- 4 and 26 +/- 8 pg/ml. In conclusion, dietary Ca restriction during lactation can stimulate CaBP and active Ca transport in both jejunum and ileum, and both parameters appear to be modulated by dietary Ca via the circulating concentration of 1,25-(OH)2D3. In contrast, in the duodenum neither parameter appears to be related to dietary Ca, plasma 1,25-(OH)2D3 concentration, or lactation-associated bone loss.

Animals

Effects of high dietary contents of calcium and phosphorus on mineral metabolism and growth of vitamin D-deficient suckling and weaned rats.

We have tested the hypothesis that normalization of the plasma calcium (Ca) and phosphorus (P) concentrations by dietary means in vitamin D-deficient rat pups will prevent rickets. From day 6 of pregnancy rats were given a vitamin D-free diet containing 1.6% Ca and 1.4% P (-D 1.6) which normalized plasma Ca during lactation. Pups weaned from these mothers, and continuing on the -D 1.6 diet until 56 days of age, had a mean plasma Ca value of 8.6 +/- 0.2 mg/dl and were not significantly different from pups fed a vitamin D-replete diet with 0.4% Ca and 0.4% P in the following parameters: body weight (mean +/- SE for -D 1.6 rats: 197 +/- 4 g), percent bone ash (53 +/- 0.5), and tibia epiphyseal cartilage width (385 +/- 26 micron). In contrast, pups consuming the vitamin D-free diet with 0.4% Ca and 0.4% P had plasma Ca of 4.9 +/- 0.2 mg/dl, body weight of 156 +/- 4 g, reduced bone ash (45 +/- 0.5%) and abnormally wide epiphyseal cartilage (727 +/- 113 micron). Thus, elevating the plasma Ca level of vitamin D-deficient rat pups by dietary means can normalize body weight, epiphyseal cartilage width and bone mineral content.

Animals