Shmuel Hurwitz's research while affiliated with Agricultural Research Organization ARO and other places

Due to the importance of Ca2+ in the regulation of vital cellular and tissue functions, the concentration of Ca2+ in body fluids is closely guarded by an efficient feedback control system. This system includes Ca(2+)-transporting subsystems (bone, and kidney), Ca2+ sensing, possibly by a calcium-sensing receptor, and calcium-regulating hormones (parathyroid hormone [PTH], calcitonin [CT], and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]). In humans and birds, acute Ca2+ perturbations are handled mainly by modulation of kidney Ca2+ reabsorption and by bone Ca2+ flow under PTH and possibly CT regulation, respectively. Chronic perturbations are also handled by the more sluggish but economic regulatory action of 1,25(OH2)D3 on intestinal calcium absorption. Peptide hormone secretion is modulated by Ca2+ and several secretagogues. The hormones' signal is produced by interaction with their respective receptors, which evokes the cAMP and phospholipase C-IP3-Ca2+ signal transduction pathways. 1,25 (OH)2D3 operates through a cytoplasmic receptor in controlling transcription and through a membrane receptor that activates the Ca2+ and phospholipase C messenger system. The calciotropic hormones also influence processes not directly associated with Ca2+ regulation, such as cell differentiation, and may thus affect the calcium-regulating subsystems also indirectly.

The interaction between growth and calcium homeostasis was studied by comparing the responses of (a) fast-growing broiler chickens (Cobb) and slow-growing Leghorns, and (b) fast-growing chickens (Cobb) fed either high energy (12.13 kJ/g) or low energy (9.2 kJ/g) diets, to dietary calcium concentration ranging between 4 and 20 g/kg). Plasma calcium increased as dietary calcium increased, reaching an apparent plateau between 0.8 and 1.5% dietary calcium, regardless of basal growth rate. Dietary calcium levels of 1.5% and higher induced hypercalcemia and hypophosphatemia in fast- but not in slow-growing chickens. Weight gain was unaffected by dietary calcium in the slow-growing Leghorns, but followed a bell-shaped response pattern in the fast-growing Cobb chickens. Growth inhibition by feeding of low energy diets changed the response pattern from a quadratic form to that of an increase towards a plateau. The response of bone ash to dietary calcium was characterized as quadratic in fast-growing chicks, changing to a pattern of increase towards a plateau in slow-growing chicks. Intestinal calbindin was suppressed by dietary calcium and was higher in the fast-growing than in the slow-growing chicks. An increase in dietary phosphorus resulted in a shift in the response curves of weight gain and bone ash and an increase in the calcium requirements. The results indicate that the response of chicks to dietary calcium and calcium requirements is markedly modified by growth rate.

1.1. At 35°C, the response functions of body weight gain and feed intake of 5–8 week old chickens to relative humidity (RH) were bell shaped with maxima at 60–65%, corresponding to minima in core and skin temperature, blood pH, and to maxima in blood pCO2.2.2. In 5–8 week old turkeys, weight gain and feed intake declined only with the increase from 40–45% to 50–55% in RH. Core and skin temperature, and blood acid-base were not affected by RH.3.3. Plasma (T3) concentration was positively correlated with feed intake.

Computer simulation of calcium homeostasis in chicks predicted an oscillatory behavior of bone calcium flow and kidney 25-hydroxyvitamin D3-1-hydroxylase with a periodicity of 56 h and a 9 h phase difference between the two signals. In growing chickens subjected to a light: dark cycle of 22:2 h, and intravenously dosed with 45Ca, the temporal changes in plasma 45Ca could be described by an exponential decline with superimposed diurnal oscillations. The activity of the renal 25-hydroxyvitamin D3-1-hydroxylase in chicks subjected to a 12:12 h light: dark cycle ALSO followed diurnal oscillations, with a nadir at the beginning of the light period and a peak 12 h later. The production of 1,25-dihydroxyvitamin D3 by primary cultures of chicken kidney cells oscillated with a periodicity of 5.6 h or shorter. It is suggested that despite the differences in phase and periodicity between the simulation predictions and actual results, the oscillations in both 1-hydroxylase and bone calcium flow could be coupled through the hormonal systems involved in regulation of plasma calcium.

Regulation of prepro-PTH and vitamin D receptor (VDR) mRNAs in the parathyroid glands was studied in chickens in vivo. The birds were raised to 21 days of age on a vitamin D-deficient diet with 1% calcium and 0.65% phosphorous. At the end of this period, the chicks exhibited marked hypocalcemia and enlarged parathyroid glands. In three separate trials, the birds were repleted for 6 days with vitamin D and different dietary calcium and phosphate concentrations, with 2 micrograms/kg 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and different dietary calcium concentrations (0.5%, 1.0%, or 1.8%), or with 2 or 10 micrograms/kg 1,25-(OH)2D3 and 0.6% or 1.9% calcium or were kept vitamin D3 deficient and fed 0.5%, 1.0%, or 1.8% dietary calcium. Vitamin D treatment when combined with a high level of dietary calcium resulted in an increase in plasma calcium from 6 mg/dl to greater than 10 mg/dl, a decrease in PTH mRNA of 65%, and a 6- to 8-fold increase in VDR mRNA. In another experiment in which no vitamin D source was given and the diets contained increasing levels of dietary calcium, plasma calcium increased significantly (5.5 vs. 7 mg/dl), while PTH mRNA decreased by 40% and VDR mRNA increased by 60%. Neither parathyroid gland weight nor total RNA was significantly affected. When chicks were repleted with 1,25-(OH)2D3, the increase in plasma calcium and VDR mRNA and the decrease in PTH mRNA were considerably more pronounced than those in the absence of the vitamin D source. Furthermore, in the presence of the hormone, parathyroid weight and total RNA decreased significantly with increasing concentrations of dietary calcium. When the chicks were repleted, respectively, with the two levels of 1,25-(OH)2D3, a marked positive interaction was evident between the hormone and dietary calcium in affecting levels of PTH and VDR mRNA. These results suggest that both 1,25-(OH)2D3 and calcium participate in the regulation of PTH and VDR gene transcription in the avian parathyroid gland. Whereas the action of 1,25-(OH)2D3 requires a minimal level of dietary calcium, calcium affects PTH and VDR gene transcription even in the absence of any vitamin D source.

Regulation of prepro-PTH and vitamin D receptor (VDR) mRNAs in the parathyroid glands was studied in chickens in vivo. The birds were raised to 21 days of age on a vitamin D-deficient diet with 1% calcium and 0.65% phosphorous. At the end of this period, the chicks exhibited marked hypocalcemia and enlarged parathyroid glands. In three separate trials, the birds were repleted for 6 days with vitamin D and different dietary calcium and phosphate concentrations, with 2 micrograms/kg 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and different dietary calcium concentrations (0.5%, 1.0%, or 1.8%), or with 2 or 10 micrograms/kg 1,25-(OH)2D3 and 0.6% or 1.9% calcium or were kept vitamin D3 deficient and fed 0.5%, 1.0%, or 1.8% dietary calcium. Vitamin D treatment when combined with a high level of dietary calcium resulted in an increase in plasma calcium from 6 mg/dl to greater than 10 mg/dl, a decrease in PTH mRNA of 65%, and a 6- to 8-fold increase in VDR mRNA. In another experiment in which no vitamin D source was ...

The involvement of vitamin D and its endocrine system is essential, both for the process of bone development and growth, as well as bone remodeling. Important bone cells participating in those processes include the osteoblast (bone formation), the osteoclast (bone resorption) and the growth plate chondrocyte (longitudinal bone growth). The hormonally active form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], generates many of the biological responses attributed to the parent vitamin D3, including actions on osteoblasts and chondrocytes and the stimulation of the production of osteoclasts. 1,25(OH)2D3 is able to generate biological responses via both genomic and nongenomic pathways. This review provides a summary of this area.

A synthetic oligonucleotide was used as a probe for measurement of calbindin mRNA in the shell gland and intestine of chickens. The half time of calbindin mRNA in the duodenum and shell gland was estimated at 2 and 3.6 h and that of calbindin at 13.9 and 32.6 h, respectively. The formation rates of calbindin mRNA were 0.37 and 0.17 pmol.h-1.g-1 and the rate of calbindin formation was 0.099 and 0.031 microgram.pmol mRNA-1.h-1 in the duodenum and shell gland, respectively. In the shell gland, calbindin mRNA and calbindin appeared at the time of sexual maturation during calcification of the first egg shell. Calbindin mRNA fluctuated markedly during the daily egg cycle, in close temporal association with egg shell calcification. When Ca2+ deposition was eliminated by expulsion of the ovum, the rise in calbindin mRNA was prevented. An indirect suppression of Ca2+ deposition by administration of the carbonic anhydrase inhibitor acetazolamide also resulted in a decrease in calbindin mRNA. The results are consistent with a possible role of Ca2+ flux in the regulation of calbindin mRNA appearance in the shell gland of chickens.

A synthetic oligonucleotide was used as a probe for measurement of calbindin mRNA in the shell gland and intestine of chickens. The half time of calbidin mRNA in the duodenum and shell gland was estimated at 2 and 3.6 h and that of calbindin at 13.9 and 32.6 h, respectively. The formation rates of calbindin mRNA were 0.37 and 0.17 pmol.h-1.g-1 and the rate of calbindin formation was 0.099 and 0.031-mu-g.pmol mRNA-1.h-1 in the duodenum and shell gland, respectively. In the shell gland, calbindin mRNA and calbindin appeared at the time of sexual maturation during calcification of the first egg shell. Calbindin mRNA fluctuated markedly during the daily egg cycle, in close temporal association with egg shell calcification. When Ca2+ deposition was eliminated by expulsion of the ovum, the rise in calbindin mRNA was prevented. An indirect suppression of Ca2+ deposition by administration of the carbonic anhydrase inhibitor acetazolamide also resulted in a decrease in calbindin mRNA. The results are consistent with a possible role of Ca2+ flux in the regulation of calbindin mRNA appearance in the shell gland of chickens.