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D D Bikle

Publications and source records attributed to D D Bikle.

At least 145 records · Page 8Linked to original sources
PubMed1983

Simulating certain aspects of hypogravity: effects on bone maturation in the non-weight bearing skeleton.

This study reports the effects of simulation of certain aspects of hypogravity (via partial skeletal unloading) on the growth and maturation of the non-weight bearing mandibles of 41-d and 1-yr-old rats. Partial skeletal unloading was effected by elevating the hindquarters (PULEH), and this simulation was controlled with normally loaded animals fed either ad libitum or the average amount of food consumed by the the experimental group (group-mean fed). The chemical status of the mandibles after 10 d or 14 d PULEH closely resembled that of control rats. The younger PULEH rats and their group-mean fed controls demonstrated a trend toward impaired maturation of mineral and matrix moieties; yet the concentrations of calcium (Ca) and phosphorus (P) expressed as a ratio to collagen hydroxyproline content were normally distributed within a density gradient profile which separates the mineral and matrix moieties into various age-dependent fractions. These data demonstrate that 10 d or 14 d PULEH in young or old rats, respectively, is not sufficient to elicit the maturation deficit observed in the mandibles of rats flown for 18.5 d in the Soviet Biosatellite Cosmos-1129. Unless the duration of PULEH is critical, the cephalad fluid shift which is common to PULEH and spaceflight animals cannot be solely responsible for the flight-induced maturation deficit. Because the mandibles of the PULEH rats remain antigravity-postured, the results emphasize the importance of gravity unloading to the impairment of mandibular bone matrix/mineral maturation during spaceflight. Decreased gravity and, hence, gravity unloading cannot be mimicked in ground-based models of hypokinesia.

Age Factors↗
PubMed1982

The vitamin D endocrine system.

In this review I have discussed out current understanding of the vitamin D endocrine system. Vitamin D is made available to the body both by intestinal absorption and by photosynthesis in the skin. To be active, vitamin D must be hydroxylated to 250HD, principally in the liver, and to 1,25(OH)2D and 24,25(OH)2D, principally in the kidney. The best studied target tissues for the vitamin D metabolites are bone, kidney, and intestine. However, the list of additional potential target tissues is expanding and includes muscle, endocrine pancreas, parathyroid gland, pituitary, and skin. Disorders of the vitamin D endocrine system can be categorized into three groups: decreased bioavailability, abnormal metabolism, and aberrant target tissue response. A number of illustrative examples for each category have been discussed. Primary biliary cirrhosis typifies the problem of vitamin D malabsorption and disrupted enterohepatic circulation; chronic renal failure is the most devastating problem of vitamin D metabolism; and vitamin D dependent rickets type II is the best example of aberrant target tissue response. However, certain disorders overlap these distinct categories. Others, such as the nephrotic syndrome, which leads to urinary losses of the vitamin D metabolites (presumably bound to DBP), are not readily categorized. Nevertheless, an understanding of the level at which the vitamin D endocrine system is perturbed by any given disorder provides a rational basis for therapeutic intervention.

Aged↗
PubMed1981

Action of vitamin D on intestinal calcium transport.

The means by which 1,25(OH)2D3 regulates calcium transport across the intestine still remains an enigma. The movement of calcium across the brush border membrane into the cell occurs down a steep concentration gradient. Stimulation of this process by 1,25(OH)2D3 occurs within 2h and does not require new protein synthesis. Although the mitochondria may be involved in moving the calcium across the cell under rather high concentrations of cytosol calcium (10(-5) M Ca), a different organelle (lysosome-like vesicle) may assume primary responsibility for intracellular transport at lower calcium concentrations. This change from mitochondrial to vesicular calcium movement requires time (within 18 h) and may involve new protein synthesis. In the absence of this changeover, calcium transport can still occur but only at the cost of higher intracellular calcium concentrations. Movement of calcium out of the cell across the basolateral membrane occurrs against a steep concentration gradient. The difficulty in preparing pure basolateral membranes with homogeneous orientation of the inner and outer surfaces has limited progress in our understanding of calcium movement across this membrane. However, the need for an energy-driven calcium pump at this membrane that is responsive to micromolar calcium concentrations is apparent. Whether 1,25(OH)2D3 induces the synthesis of such a pump or leads to its activation by factors such as CaBP, cAMP, and calmodulin remains to be determined.

Animals↗
PubMed1981

In vitro stimulation of 25-hydroxycholecalciferol 1 alpha-hydroxylation by parathyroid hormone in chick kidney slices: evidence for a role for adenosine 3',5'-monophosphate.

We studied the effect of parathyroid hormone (PTH) on the in vitro conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] by kidney slices from vitamin D-deficient chicks. Bovine PTH (bPTH) stimulated 1,25-(OH)2D3 production at low concentrations, with maximal stimulation (65%) at a concentration of 25 ng/ml bPTH in the absence of theophylline. Higher concentrations of bPTH resulted in less stimulation. The addition of 5 mM theophylline to the incubation buffer decreased basal 1,25-(OH)2D3 production but potentiated the stimulation of 1,25-(OH)2D3 production by PTH. Maximal stimulation (170%) was observed with 2 ng/ml bPTH in the presence of theophylline. Maximal stimulation of cAMP production by the kidney slices required 2- to 3-fold larger concentrations of bPTH. However, cAMP by itself stimulated 1,25-(OH)2D3 production, with maximal stimulation (70%) at 10(-7)-10(-5) M cAMP. We conclude that stimulation by PTH of 1,25-(OH)2D3 production can be potentiated by theophylline and mimicked by cAMP. However, such stimulation occurs at PTH concentrations lower than that required for optimal stimulation of adenylate cyclase activity.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1980

Studies of the chick renal mitochondrial 25-hydroxyvitamin D-3 24-hydroxylase.

The vitamin D metabolite, 24,25-dihydroxyvitamin D-3, is made from 25-hydroxyvitamin D-3 by an enzyme (25-hydroxyvitamin D-3 24-hydroxylase) located in the renal mitochondria of vitamin D and calcium-replete chicks. The apparent Km for 25-hydroxyvitamin D-3 for this reaction was found to be 3 x 10(-7) M, although simple Michaelis-Menten kinetics were not observed at the higher substrate concentrations. Enzymatic activity was reduced by the mitochondrial metabolic inhibitors, antimycin A and dinitrophenol, as well as the inhibitors of mixed function oxidases, 2,4-dichloro-6-phenylphenoxyethylamine, 2-diethylaminoethyl-2,2-diphenylvalerate and metyrapone. Increasing the calcium concentration from 0 to 1 x 10(-5) M or the potassium concentration from 0 to 50 mM stimulated enzymatic activity 4- to 8-fold. Increasing the phosphate or acetate concentration from 0 to 50 mM stimulated enzymatic activity 6-fold. Raising the CO2/HCO3(-) content from 0/0 to 10%/10 mM stimulated enzymatic activity 5-fold. The effects of the cations were additive to those of the anions except in the presence of 50 mM phosphate or acetate. The effect of ions on 24,25-hydroxyvitamin D-3 production by renal mitochondria from vitamin D-replete chicks resembles the effect of these ions on production of 1,25-dihydroxyvitamin D-3 by renal mitochondria from vitamin D-deficient chicks, suggesting that the same mechanisms may be utilized.

Acetates↗
PubMed1980

Calcium accumulation by chick intestinal mitochondria. Regulation by vitamin D-3 and 1,25-dihydroxyvitamin D-3.

We have the evaluated the effect of vitamin D-3 and its metabolite 1,25-dihydroxyvitamin D-3 on Ca2+ accumulation by chick intestinal mitochondria. Ca2+ accumulation appears to occur in two phases: an early, transient accumulation into an Na+-labile pool followed by an ATP-dependent accumulation into an Na+-resistant pool. Ca2+ accumulation is extensive at free Ca2+ concentrations greater than 3 . 10(-6) M in the presence of ATP. Ruthenium red and dinitrophenol block Ca2+ accumulation, but atractyloside does not. Oligomycin blocks ATP-supported accumulation completely with a partial inhibition of ATP and malate-supported accumulation. Little difference could be found in mitochondrial preparations from vitamin D-deficient chicks compared to those from vitamin D-3 (or 1,25(OH)2D-3)-supplemented chicks with respect to respiratory control, oxygen consumption, efficiency of oxidative phosphorylation, affinity for Ca2+, or the rate and extent of ATP-supported Ca2+ accumulation. Intestinal cytosol stimulated Ca2+ accumulation, but this was not specific with respect to vitamin D status or tissue of origin, nor was it duplicated by chick intestinal Ca2+-binding protein. 30 ng/ml 1,25(OH)2D-3 stimulated Ca2+ accumulation directly, regardless of the presence of intestinal cytosol. Other vitamin D metabolites were less potent: 25-hydroxyvitamin D-3 greater than 24,25-dihydroxyvitamin D-3 = vitamin D-3. Since increasing the free Ca2+ concentration from 3 . 10(-6) to 1 . 10(-5) M increased Ca2+ accumulation approx. 50-fold, whereas direct stimulation by 1,25(OH)2D-3 in vitro increased Ca2+ accumulation less than 2-fold, we conclude that 1,25(OH)2D-3 influences mitochondrial accumulation of Ca2+ in vivo primarily by altering cytosol concentrations of free Ca2+.

Adenosine Triphosphate↗
PubMed1980

Prolactin but not growth hormone stimulates 1,25-dihydroxyvitamin D3 production by chick renal preparations in vitro.

We studied the effect of PRL from two species (bovine and turkey) and GH from two species (bovine and turkey) on 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] production by two whole cell preparations from vitamin D-deficient chick kidneys (slices and tubules). We observed that 8 ng/ml turkey PRL stimulated 1,25(OH)2D3 production by renal tubules and slices. Ovine PRL had a similar effect on 1,25(OH)2D3 production but at higher concentrations. In contrast, neither bovine GH nor turkey GH stimulated 1,25(OH)2D3 production appreciably at doses up to 1000 ng/ml. The effect of PRL on 1,25(OH)2D3 production by renal tubules required a 3-h preincubation, although its effect on 1,25(OH)2D3 production by renal slices was immediate. We conclude that PRL, but not GH, directly stimulates 1,25(OH)2D3 production by the chick kidney.

Animals↗
PubMed1979

Work-induced muscle hypertrophy in vitamin D-deficient rats.

To determine if vitamin D deficiency would retard the ability of muscle to hypertrophy in response to mechanical stress, we severed the gastrocnemius tendon on one leg of rats in each of three groups, the treatment of which differed only in the amount of vitamin D in the diet. After 1 week the increased size of the soleus and plantaris in the leg in which the gastrocnemius was severed relative to that of the sham operated leg, was determined for each rat. Despite differences in body weight and serum calcium among the groups, we found no difference in the percent of muscle hypertrophy. We conclude that muscle hypertrophy can occur in response to local mechanical forces despite a deficient hormonal environment that otherwise retards growth.

Animals↗
PubMed1979

Stimulation of chick gut alkaline phosphatase activity by actinomycin D and 1,25-dihydroxyvitamin D3: evidence for independent mechanisms.

We observed that inhibitors of RNA synthesis, actinomycin D and cordycepin, stimulate chick duodenal alk Pase activity by means which are additive to the stimulaation by the biologically active metabolite of vitamin D3, 1,12(OH)2D3, and its analogue, 1 alpha OH D3. The protein synthesis inhibitor, cycloheximide, inhibited basal alk Pase activity and blocked its stimulation by actinomycin D and 1,25(OH)2D3. Both actinomycin D and cycloheximide blocked the ability of 1,25(OH)2D3 and 1 alpha OHD3 to raise serum calcium levels. The paradoxical stimulation of duodenal alk Pase activity by RNA synthesis inhibitors additive to the stimulation by 1,25(OH)2D3 suggests that alk Pase activity is controlled by mechanisms other than gene activation. (J LAB CLIN MED 94:88, 1979.)

Alkaline Phosphatase↗
PubMed1978

Independence of 1,25-dihydroxyvitamin D3-mediated calcium transport from de novo RNA and protein synthesis.

The administration of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to rachitic chicks produces an increase in (a) RNA and protein synthesis, (b) calcium binding protein (CaBP) concentration, and (c) alkaline phosphatase activity in the duodenum. These events occur concomitantly with enhanced calcium transport. We inhibited RNA and protein synthesis in richitic chicks and measured the subsequent response to 1,25(OH)2D3. Actinomycin D, injected prior to and following 1,25(OH)2D3 administration, inhibited intestinal RNA polymerase activity, blocked the rise in serum calcium, reduced the amount of CaBP, and increased alkaline phosphatase activity. Cycloheximide injected in similar fashion, inhibited the 1,25(OH)2D3-mediated increase in intestinal protein synthesis, serum calcium, CaBP, and alkaline phosphatase activity. Neither inhibitor blocked the ability of 1,25(OH)2D3 to stimulate calcium transport as measured in isolated duodenal loops in vivo. The ability of either inhibitor to block 1,25(OH)2D3-mediated calcium transport despite inhibition of CaBP production and alkaline phosphatase activity (by cycloheximide) indicates that de novo RNA and protein synthesis, and in particular CaBP and alkaline phosphatase, are not required for the 1,25(OH)2D3 stimulation of calcium transport.

Alkaline Phosphatase↗