Serum intact parathyroid hormone levels in elderly Chinese females with hip fracture

Summary Serum intact parathyroid hormone (PTH), 25 hydroxyvitamin D(25OHD), 1,25 dihydroxyvitamin D (1,25(OH)₂D), albumin, and ionized calcium were measured in 61 Chinese female patients with hip fracture and 61 control subjects. Hip fracture patients had low albumin, ionized calcium, and 250HD levels. Serum PTH and 1,25 (OH)₂D values were not different between the two groups. We conclude that although 250HD level in hip fracture patients is low, there is no evidence of secondary hyperparathyroidism, suggesting that the low 250HD levels may be a secondary phenomenon in response to the fracture.     

The effect of endogenous estrogen fluctuation on metabolism of 25-hydroxyvitamin D

Summary To test the hypothesis that estrogen modulates the metabolism of 25-hydroxyvitamin D (25(OH)D) to 1,25-dihydroxyvitamin D (1,25(OH)₂D) and 24, 25-dihydroxyvitamin D (24, 25(OH)₂D), we studied 20 normal premenopausal women at four consecutive weekly intervals during one menstrual cycle. Estrogen stimulation was semiquantitatively defined into baseline, lowgrade, or medium-grade categories, based on endogenous estrone and estradiol concentrations. 1,25(OH)₂D increased incrementally from baseline levels of 34±3(SE) pg/ml to 39±3 pg/ml (P=0.2) with low-grade estrogen stimulation and to 43±3 pg/ml (P<0.05) with medium-grade estrogen stimulation, while 25(OH)D, 24,25(OH)₂D, vitamin D binding protein, parathyroid hormone, calcium, and phosphate did not change. 24,25(OH)₂D was correlated to 25(OH)D at baseline (r=0.65,P<0.01) and with low-grade estrogen stimulation (r=0.062,P<0.01), but not with medium-grade stimulation (r=0.13); these relationships are consistent with the concepts that 25(OH)D is metabolized predominantly to 24,25(OH)₂D at low estrogen levels, but not at higher estrogen levels. We conclude that endogenous estrogen elevation promotes formation of 1,25(OH)₂D from 25(OH)D, and that it may reciprocally inhibit synthesis of 24,25(OH)₂D.     

1,25(OH)2D and 24,25(OH)2D production in the developing kidney

To clarify the state of vitamin D production by the developing kidney, firstly, we measured serum levels of 1,25(OH)₂D and 24,25(OH)₂D in humans of different ages (pregnant and nonpregnant women, adult males, children and newborn infants) and secondly, we measured 1- and 24-hydroxylase activity in the kidney mitochrondria of rats at different ages. The mean serum levels of 1,25(OH)₂D in pregnant women, cord blood and newborns were significantly higher than those in children and non-pregnant women and adult males. In newborns, the level increased with gestational age. Synthesis of 1,25(OH)₂D was, at least in part, under the control of the fetus and newborn, rather then being solely a reflection of the conditions prevailing in the mother. The 1-hydroxylase activity in mitochondria was highest in the 1- to 2-month-old rats, and it decreased gradually thereafter. The change in 1-hydroxylase activity with age was due to a change in the V_max of the system.     

Vitamin D Does Not Increase Calcium Absorption in Young Women: A Randomized Clinical Trial

It is commonly said that vitamin D should be used to increase calcium absorption. We tested this statement in a dose‐response study of vitamin D on calcium absorption. A total of 198 white and African American women, aged 25 to 45 years, with vitamin D insufficiency, serum 25‐hydroxyvitamin D (25OHD) <20 ng/mL, were randomized in a double‐blind study to vitamin D3 400, 800, 1600, 2400 IU, or placebo. A calcium supplement was given to increase mean calcium intake at baseline from 706 mg/d to 1031 mg/d. Calcium absorption was measured at baseline and after 12 months using a single isotope method with radiocalcium45 and 100 mg of calcium. Mean baseline serum 25OHD was 13.4 ng/mL (33.5 nmol/L) and increased to 40 ng/mL (100 nmol/L) on the highest dose of 2400 IU. Using a multivariate regression analysis with significant predictors, baseline absorption, calcium intake, and weight, there was no increase in 12‐month calcium absorption compared with baseline on any dose of vitamin D in either whites or African Americans. There was no significant relationship between 12‐month calcium absorption and final serum 25OHD. In an analysis of calcium absorption and serum 25OHD at baseline, serum 25OHD levels were divided into groups: 0 to 5, 6 to 10, 11 to 15, or 16 to 20 ng/mL. There was no evidence of a threshold decrease in calcium absorption or serum 1,25 dihydroxyvitamin D (1,25(OH)₂D) amongst the lowest groups. Vitamin D doses up to 2400 IU daily did not increase calcium absorption. No threshold level of serum 25OHD for calcium absorption was found at baseline or in the longitudinal study, suggesting that active transport of calcium is saturated at very low serum 25OHD levels <5 ng/mL. There is no need to recommend vitamin D for increasing calcium absorption in normal subjects. Very efficient calcium absorption at very low levels of serum 25OHD explains why people do not develop osteomalacia provided that dietary intakes of calcium and phosphorus are adequate. © 2014 American Society for Bone and Mineral Research.     

Serum calcium regulating hormones in the perinatal period

To clarify perinatal vitamin D metabolism, we measured 25-hydroxyvitamin D (25OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D], 1,25-dihydroxyvitamin D [1,25(OH)2D], calcium (Ca), phosphorus (P), parathyroid hormone (PTH), and human calcitonin (CT) in paired maternal, cord, and infant serum. Cord serum 25OHD was significantly lower than the maternal level, and cord serum 24,25(OH)2D was also significantly below the maternal concentrations. Maternal, cord, and infant serum 1,25(OH)2D, on the other hand, was significantly higher than the normal adult level. The serum PTH was low, but the CT concentration was high in the cord. Cord serum Ca and P levels were significantly higher than maternal. The reason for the elevated circulating 1,25(OH)2D level in the perinatal period is uncertain, and we speculate that the possible factors are gonadal steroids, placental lactogen, prolactin, and CT. In addition, serum 24,25(OH)2D and 1,25(OH)2D concentrations are under some control by the fetus.     

Comparison of vitamin D metabolism in early healthy and late osteoporotic postmenopausal women

Summary We studied 20 healthy premenopausal women aged 36.5±4.0 years (mean±1 SD), 123 healthy postmenopausal women aged 50.0±2.4 years, and 103 postmenopausal women aged 65.1±5.6 years with symptomatic osteoporosis (forearm and spinal fracture). Serum levels of vitamin D metabolites [25(OH)D, 24,25(OH)₂D₃, and 1,25(OH)₂D] were compared with (1) bone mass in the forearm (single photon absorptiometry) and in the spine (dual photon absorptiometry); (2) biochemical indices of bone formation (serum alkaline phosphatase, plasma bone Gla protien), and bone resorption (fasting urinary hydroxyproline); and (3) other biochemical estimates of calcium metabolism (serum calcium, serum phosphate, 24-hour urinary calcium, intestinal absorption of calcium). The present study revealed no difference in any of the vitamin D metabolites between the premenopausal women, the healthy postmenopausal women and the osteoporotic women as a group. The concentrations of 1,25(OH)₂D and 25(OH)D were significantly lower in patients with spinal fracture than in those with forearm fracture. In the early postmenopausal women, serum 1,25(OH)₂D was related to forearm bone mass (r=−0.20;P<0.05), intestinal calcium absorption (r=0.18;P<0.05), and 24-hour urinary calcium (r=0.21;P<0.05); serum 25(OH)D was related to spinal bone mass (r=0.23;P<0.01). In the osteoporotic women, serum vitamin D metabolites were not related to bone mass, but 1,25(OH)₂D was related to bone Gla protein (r=0.33;P<0.001), serum phosphate (r=−0.27;P<0.01), and 24-hour urinary calcium (r=0.43;P<0.001). The present study demonstrates that in a population that is apparently not deficient in vitamin D, a disturbance of the vitamin D metabolism is not likely to play a pathogenetic role in early postmenopausal bone loss. Patients with spinal fractures have low levels of vitamin D metabolites, which may aggravate their osteoporosis.     

Hypercalcemia associated with increased circulating 1,25 dihydroxyvitamin D in a patient with pulmonary tuberculosis

Summary Studies are described in a 53-year-old man with far-advanced pulmonary tuberculosis who developed transient increases in circulating 1,25 dihydroxyvitamin D (1,25(OH)₂D) and hypercalcemia while on antituberculous treatment. Serial dilution of an extract of the patient's serum obtained while he was hypercalcemic displaced [³H]-1,25(OH)₂D₃ from chick intestinal receptor in a manner identical to authentic 1,25(OH)₂D₃. Serum 25-hydroxyvitamin D (25OHD) was suppressed during the abnormal elevation of serum 1,25(OH)₂D. It is concluded that tuberculosis is another chronic granulomatous disease in which hypercalcemia may result from abnormal metabolism of vitamin D.     

Serum 1,25-dihydroxyvitamin D concentration in hypophosphatemic vitamin D-resistant rickets

Summary Fasting serum 1α,25-dihydroxyvitamin D (1,25-(OH)₂D) levels were measured in 3 groups of hypophosphatemic vitamin D-resistant rickets (VDRR) patients: those untreated; those treated with vitamin D and phosphate; and those treated with 1,25-(OH)₂D₃ and phosphate. In the untreated patients, the mean 1,25-(OH)₂D level was higher than in our age-matched control group. Except for one at 66 pg/ml, individual values were however within normal limits. Long term vitamin D₂ therapy was accompanied by a slight but significant decrease in 1,25-(OH)₂D concentrations; nonetheless the levels remained within the normal range. In the third group of patients, the concentration of 1,25-(OH)₂D rose to supranormal levels when sampling was done 1–3 hours after administration of the hormone, decreasing rapidly to levels below that of normal subjects when the specimens were collected 12–24 hours later. Our data show that an alteration of the vitamin D activation pathway is unlikely to be part of the pathogenic mechanism underlying the VDRR condition. Calcitriol (1α,25-(OH)₂D₃) as Rocaltrol^R in capsules of 0.25 and 0.50 μg was kindly supplied by Dr. Patrick Le Morvan (Hoffmann-La Roche Ltd, Vaudreuil, Que., Canada).     

Calcium,vitamin D-endocrine system,and parathyroid hormone in black and white males

Summary The serum and urinary calcium, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), and parathyroid hormone (PTH) were studied in healthy black and white males living in Belgium, and the results were compared to data in blacks of similar age living in Za?re. Dietary calcium and vitamin D were estimated in a subsample of blacks and whites examined in Belgium. Compared to whites (9.51±0.28 mg%) serum calcium was somewhat lower in blacks (9.26±0.27 mg% in Belgium; 9.19±0.48 mg% in Za?re). The 24 hour urinary calcium excretion averaged 215.0±16.7 mg% in whites and was higher (P<0.05 or less) than in blacks (115±71 mg% in Belgium; 36±33 mg% in Za?re). The serum 25OHD levels were similar in whites and blacks evaluated in Za?re, both being higher (P<0.05 or less) than in blacks living in Belgium. In the latter blacks, an inverse correlation was observed between the 25OHD level and the duration of the stay in a temperate climate. Parathyroid hormone levels were slightly higher in blacks living in Belgium than in the other two groups of subjects. The serum levels of 1,25(OH)₂D₃ and human vitamin D-binding protein were similar in the three groups of subjects. Dietary calcium averaged 541±152 mg/day in blacks and was significantly (P<0.001) less than in whites (1,203±508 mg/day), whereas no significant difference was observed in dietary vitamin D intake between blacks and whites. It is concluded that calcium intake is low in blacks but stimulation of parathyroid hormone and 1,25(OH)₂D₃ required to achieve normocalcemia does not occur.     

Effect of 1,25(OH)2D3 and 24,25(OH)2D3 on calcium ion fluxes in costochondral chondrocyte cultures

Summary Vitamin D₃ metabolites have been shown to affect proliferation, differentiation, and maturation of cartilage cells. Previous studies have shown that growth zone chondrocytes respond primarily to 1,25(OH)₂D₃ whereas resting zone chondrocytes respond primarily to 24,25(OH)₂D₃. To examine the role of calcium in the mechanism of hormone action, this study examined the effects of the Ca ionophore A23187, 1,25(OH)₂D₃, and 24,25(OH)₂D₃ on Ca influx and efflux in growth zone chondrocytes and resting zone chondrocytes derived from the costochondral junction of 125 g rats. Influex was measured as incorporation of⁴⁵Ca. Efflux was measured as release of⁴⁵Ca from prelabeled cultures into fresh media. The pattern of⁴⁵Ca influx in unstimulated (control) cells over the incubation period was different in the two chondrocyte populations, whereas the pattern of efflux was comparable. A23187 induced a rapid influx of⁴⁵Ca in both types of chondrocytes which peaked by 3 minutes and was over by 6 minutes. Influx was greatest in the growth zone chondrocytes. Addition of 10⁻⁸–10⁻⁹ M 1,25(OH)₂D₃ to growth zone chondrocyte cultures results in a dose-dependent increase in⁴⁵Ca influx after 15 minutes. Efflux was stimulated by these concentrations of hormone throughout the incubation period. Addition of 10⁻⁶–10⁻⁷ M 24,25(OH)₂D₃ to resting zone chondrocytes resulted in an inhibition in ion efflux between 1 and 6 minutes, with no effect on influx during this period. Efflux returned to control values between 6 and 15 minutes.⁴⁵Ca influx was inhibited by these concentrations of hormone from 15 to 30 minutes. These studies demonstrate that changes in Ca influx and efflux are metabolite specific and may be a mechanism by which vitamin D metabolites directly regulated chondrocytes in culture.     

The influence of age on bone mineral regulating hormones

The objective of this study was to determine the effect of age on the blood levels of 1,25-dihydroxyvitamin D (1,25(OH)₂D) and immunoreactive parathyroid hormone (iPTH) in normal, healthy males and females. A total of 855 normal subjects (361 males and 494 females) were studied. The results show that for healthy males, blood concentrations of 1,25(OH)₂D remained essentially constant with increasing age up to age 65, and then the concentrations decreased significantly. For healthy females, 1,25(OH)₂D increased up to age 65, and then decreased at a significant rate. Serum iPTH in males increased with advancing age, but the rate of increase was greater after age 65. In females a significant increase in iPTH concentrations did not occur until after age 65. Serum creatinine increased in both males and females with advancing age.     

Studies in a patient with tumor-induced hypophosphatemic osteomalacia

Summary A 7-year study of a patient with tumor (hemangiopericytoma)-induced hypophosphatemic osteomalacia (TIO) is presented, and the findings are in keeping with the depressed tubular reabsorption of phosphate and low 1,25(OH)₂ vitamin D levels seen in other studies. Despite normalization of 1,25(OH)₂ vitamin D levels with pharmacologic doses of vitamin D₂, there was no discernible effect on serum phosphorus levels. Also, despite hypercalcemia induced by pharmacologic doses of vitamin D₂, serum parathyroid hormone levels were persistently elevated, and gradually returned to subnormal levels after removal of the tumor. Following removal of the tumor, there was a rapid increase of the 1,25(OH)₂ vitamin D levels to supraphysiologic levels, prompt appropriate increase in tubular reabsorption of phosphate levels, and symptomatic improvement in the osteomalacia. Speculations on the physiologic and pathophysiologic role of the putative hormone(s) produced by the tumors associated with this syndrome are presented.     

Immobilization decreases duodenal calcium absorption through a 1,25-dihydroxyvitamin D-dependent pathway

Immobilization induces significant and progressive bone loss, with an increase in urinary excretion and a decrease in intestinal absorption of calcium. These actions lead to negative calcium balance and the development of disuse osteoporosis. The aims of this study were to evaluate the molecular mechanisms of decreased intestinal calcium absorption and to determine the effect of dietary 1,25-dihydroxyvitamin D [1,25(OH)₂D] and a high-calcium diet on bone loss due to immobilization. The immobilized rat model was developed in the Bollman cage III to induce systemic disuse osteoporosis in the animals. There was a significant decrease in lumbar bone mineral density (BMD) and intestinal calcium absorption in the immobilized group compared with the controls. Serum 25-hydroxyvitamin D concentration did not change, but 1,25(OH)₂D concentration decreased significantly. The mRNA levels of renal 25-hydoxyvitamin D 24-hydroxylase (24OHase) increased, whereas those of renal 25-hydroxyvitamin D 1-alpha hydroxylase (1α-hydroxylase), duodenal transient receptor potential cation channel, subfamily V, member 6 (TRPV6), TRPV5, and calbindin-D9k were all decreased. A high-calcium diet did not prevent the reduction in lumbar BMD or affect the mRNA expression of proteins related to calcium transport. Dietary administration of 1,25(OH)₂D increased the intestinal calcium absorption that had been downregulated by immobilization. TRPV6, TRPV5, and calbindin-D9k mRNA levels were also upregulated, resulting in prevention of the reduction in lumbar BMD. Therefore, it is concluded that dietary 1,25(OH)₂D prevented decreases in intestinal calcium absorption and simultaneously prevented bone loss in immobilized rats. However, it remains unclear that calcium absorption and expression of calcium transport proteins are essential for the regulation of lumbar BMD.     

Serum vitamin D metabolites in younger and elderly postmenopausal women

Summary Previous investigations have suggested that a lower-than-normal serum 1,25(OH)₂D is found in elderly women with postmenopausal osteoporosis. We examined the fundamental aspects of this theory by investigating serum vitamin D metabolites infour representative samples of Caucasian women. These included 44 early postmenopausal women divided intotwo subgroups: fast bone losers, that is, bone loss>3%/year (n=20), and “physiological” bone loss (n=24); and 28 70-year-old women divided intotwo subgroups: with and without osteoporotic fractures. Serum 1,25(OH)₂D concentrations were virtually the same in all groups thus contradicting the previous reports of low 1,25(OH)₂D in elderly women. Furthermore, mean 25OHD and 24,25(OH)₂D did not differ between the groups. We conclude that 1,25(OH)₂D is unlikely to be significant in the development or treatment of a majority of women with postmenopausal osteoporosis.     

Malabsorption of calcium in corticosteroid-induced osteoporosis

Summary We have examined the relation between radiocalcium absorption and serum 1,25-dihydroxy-vitamin D [1,25(OH)₂D₃] levels in a set of 60 postmenopausal women on corticosteroid therapy (29 with and 31 without vertebral compression fractures) and compared these results with those from 31 normal postmenopausal women age-matched with the “normal” corticosteroid-treated women. Radiocalcium absorption was a function of serum 1,25(OH)₂D₃ in both corticosteroid-treated groups and in the set as a whole, but the impaired calcium absorption in the corticosteroid-treated patients with osteoporosis was not accounted for by their slightly reduced serum 1,25(OH)₂D₃ levels. This apparent resistance to the intestinal action of 1,25(OH)₂D₃ was quantified by a Z score which expresses, in standard deviation units, the difference between the measured calcium absorption and that predicted from the 1,25(OH)₂D₃ level. The Z score was significantly reduced in the osteoporotic group. Vertebral mineral density (VMD) was measured by quantitative computed tomography in 43 of the corticosteroid-treated cases and in all the normal postmenopausal women; analysis by VMD yielded similar conclusions.     

Control of plasma 1,25-(OH)2-vitamin D concentrations by calcium and phosphorus in the rat: Effects of hypophysectomy

Summary The mechanism by which dietary phosphate deprivation elevates plasma 1,25-(OH)₂-D levels is not known. To evaluate the role of the pituitary in regulating plasma 1,25-(OH)₂-D concentrations, the responses of plasma 1,25-(OH)₂-D to dietary phosphate deprivation and, separately, to dietary calcium deprivation were evaluated in intact and hypophysectomized male rats. Among intact and hypophysectomized rats eating normal diets, plasma 1,25-(OH)₂-D levels averaged 228±76 and 148±62 pmol/1, respectively (P<0.01). During dietary phosphate deprivation, plasma 1,25-(OH)₂-D levels rose to 1160±260 in intact rats and fell to 90±26 pmol/l in hypophysectomized rats (P<0.001). By contrast, during dietary calcium deprivation, plasma 1,25-(OH)₂-D levels rose in both intact and hypophysectomized animals to 856±107 and 742±279 pmol/l, respectively (NS). In response to dietary phosphate deprivation, serum calcium concentrations rose as 1,25-(OH)₂-D concentrations rose in intact rats but remained at control levels in hypophysectomized rats. These results support the hypothesis that a pituitary hormone acting either directly or indirectly on the kidney mediates the increase in plasma 1,25-(OH)₂-D during dietary phosphate deprivation. The hypercalcemia that occurs in rats during dietary phosphate deprivation appears to depend on the elevation of plasma 1,25-(OH)₂-D.     

The influence of dihydroxylated vitamin D metabolites on bone formation in the chick

Summary The ability of 1,25(OH)₂D₃ and of 24,25(OH)₂D₃ to prevent or to heal rickets in chicks was evaluated by studies of plasma biochemistry, growth plate histology, bone morphometry and microradiography, and bone mineralization. 1,25(OH)₂D₃ at a dose of 100 ng/day produced fewest abnormalities compared with vitamin D₃-treated control chicks. Bone growth was slightly greater than vitamin D₃-treated controls in chicks given a lower dose of this metabolite; the reverse was observed in chicks given a higher dose. 24,25(OH)₂D₃ was less effective than 1,25(OH)₂D₃ in preventing rickets even at doses as high as 400 ng/day. Treatment of rachitic chicks with doses of 24,25(OH)₂D₃ up to 300 ng/day produced no healing effect on the bone lesions, in marked contrast to the beneficial effects observed with 1,25(OH)₂D₃.     

Oral 1,25-dihydroxyvitamin D3 loading test in normal subjects and patients with chronic renal failure under haemodialysis

Summary: The present study was designed to determine the criterion for 1,25-dihydroxyvitamin D₃ (1,25 (OH)₂D₃) loading test in normal subjects and haemodialysis patients. Fourteen normal subjects were administered 1.0 μg of 1,25(OH)₂D₃ per os and serum 1,25(OH)₂D was monitored every hour up to 6 h afterwards under conditions of overnight fasting, and six haemodialysis patients were administered 2.0 μg of 1,25(OH)₂D₃ per os and serum 1,25(OH)₂D was monitored every 2 h up to 12 h afterwards. Peak time of serum 1,25 (OH)₂D varied between 2 and 5 h after administration in normal subjects. However, there was a good correlation between the maximum increment of 1,25(OH)₂D (maxΔ1,25(OH)₂D) and the increment at 4 h after administration (Δ1,25(OH)₂D(4 h)). the peak time of Δ1,25(OH)₂D in six haemodialysis patients was also at 4 h after administration. From these observations, Δ1,25(OH)₂D(4 h) was evaluated in subsequent studies. Twenty-six normal subjects and 24 haemodialysis patients were administered 0.5–2.0 μg of 1,25(OH)₂D₃ per os, according to their bodyweights, under conditions of overnight fasting. Blood samples were drawn for measuring 1,25(OH)₂D prior to and 4 h after administration. Δ1,25(OH)₂D(4 h) showed good correlation with the dose of 1, 25 (OH)2D3 adjusted by bodyweight (ng/kg bodyweight). the ratio of Δ1,25(OH)₂D(4 h) and adjusted dose of 1,25(OH)₂D₃ was more than 2.0 in all normal subjects (range: 1.97?2.89, mean ± SD: 2.38 ± 0.287). Moreover, the ratio of Δ1,25(OH)₂D(4 h) and adjusted dose of 1,25(OH)₂D₃ showed a good reproducibility (CV%= 5.7 Δ 0.32, n=5), and did not depend on the administered dose of 1,25(OH)₂D₃, suggesting that this ratio is a good parameter for the intestinal absorption of 1,25(OH)₂D₃. In haemodialysis patients, the mean ratio of Δ1,25 (OH)₂D(4 h) and adjusted dose of 1,25(OH)₂D₃ was 2.14 Δ 0.489, which was not significantly different from the ratio in normal subjects, suggesting that, fundamentally, there was no impairment of intestinal absorption of 1,25(OH)₂D₃ in these patients. However, low ratios of Δ(4 h) and the dose of 1,25(OH)₂D₃ with low basal levels of 1,25(OH)₂D were observed in some patients (less than 1.5 in four patients), suggesting that there exist haemodialysis patients with malabsorption of 1,25(OH)₂D₃. From these results, the criterion for normal response in 1,25(OH)₂D loading test was proposed, namely, that the ratio of Δ1,25(OH)₂D(4 h) and adjusted dose of 1,25(OH)₂D₃ be more than 2.0.     

Actions of parathyroid hormone and 1,25-dihydroxycholecalciferol on citrate decarboxylation in osteoblast-like bone cells differ in calcium requirement and in sensitivity to trifluoperazine

Summary The actions of PTH in OB bone cells appear to involve both calcium and cAMP. At present little information exists regarding the relationship, if any, between these two putative second messengers of hormone action in bone cells. In this report the molecular role of calcium in the actions of PTH and 1,25(OH)₂D₃ has been compared, since like PTH, the steroid 1,25(OH)₂D₃ is a potent bone resorbing hormone that exerts inhibition of citrate decarboxylation in OB cells, but unlike PTH does not activate adenylate cyclase. It was found that 1,25(OH)₂D₃ could initiate near maximum inhibition of citrate decarboxylation at extracellular calcium levels as low as 0.05 mM, whereas PTH effects began to be apparent only at 0.1 mM calcium, and maximum inhibition of citrate decarboxylation by PTH required 0.5 mM Ca. In addition, PTH-induced decrease in citrate decarboxylation was inhibited by low doses of TFP, an inhibitor of calmodulin and calcium-dependent, phospholipid-sensitive protein kinases, in contrast to 1,25(OH)₂D₃, whose effects were not reduced by this agent. These results suggest that: (a) the actions of 1,25(OH)₂D₃ may not be directly dependent on calcium influx; (b) in OB cell response to PTH a relationship probably exists between cAMP and calcium; and (c) this relationship may involve calmodulin, or calcium-dependent protein kinases that can be inhibited by TFP.     

Influence of exogenous porcine growth hormone on vitamin D metabolism and calcium and phosphorus absorption in intact pigs

The influence of growth hormone (GH) on vitamin D metabolism and calcium and phosphorus absorption in vivo is not clear. We, therefore, measured calcium and phosphorus balance, plasma 1,25-dihydroxyvitamin D (1,25(OH)₂D), and intestinal vitamin D-dependent calcium-binding protein (CaBP 9k) in intact growing pigs given exogenous GH. Six 10-week-old pigs were given two daily subcutaneous injections of 50 g porcine GH/kg body weight for 2 months; six control pigs were given vehicle. They were all fed a diet containing 1.1% Ca, 0.6% P, and 1000 IU vitamin D₃/kg. Apparent Ca and P absorption and retention were measured in a 10-day balance trial at the end of the 2 months. The plasma levels of Ca, P, 1,25(OH)₂D, IGF-I, and GH were determined, and the duodenal and jejunal mucosal CaBP 9k content was measured at slaughter. The plasma Ca and P of GH-treated pigs were unchanged, but all aspects of mineral metabolism, including the plasma 1,25(OH)₂D concentration (40%), Ca absorption and retention (70%), P absorption (33%) and retention (45%), and jejunal CaBP 9k (40%), were stimulated, in addition to an increase in the circulating IGF-I concentration.