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Biomedical subjects

J D Wark

Publications and source records attributed to J D Wark.

At least 91 records · Page 5Linked to original sources

Risk factors for stress fractures in female track-and-field athletes: a retrospective analysis.

The incidence and nature of stress fractures and the relationship of potential risk factors to stress-fracture history were investigated retrospectively in a group of 53 female competitive track-and-field athletes. Forty-five stress fractures, diagnosed by clinical findings and bone scan, radiograph, or CT scan, were reported in 22 women. Tibial fractures were the most common (33%). There was no significant difference in bone mineral density at the lumbar spine and tibia/fibula or in percentage body fat and total lean mass when comparing the groups with and without a stress-fracture history. Athletes with a past stress fracture were significantly older at menarche and were more likely to have experienced a history of menstrual disturbance (p < 0.05). Analysis of dietary behavior found that athletes with stress fractures scored significantly higher on the EAT-40 test and were more likely to engage in restrictive eating patterns and dieting. Multiple logistic regression showed that athletes with a history of oligomenorrhea were six times more likely to have sustained a stress fracture in the past, while those who were careful about their weight were eight times more likely. Prevention and treatment of stress fractures in female athletes should include a thorough assessment of menstrual characteristics and dietary patterns.

Adipose Tissue↗

Bone density, vitamin D nutrition, and parathyroid hormone levels in women with dementia.

OBJECTIVE: To determine whether patients with dementia have reduced bone mass, altered vitamin D, or parathyroid hormone status. DESIGN: Survey. SETTING: University hospital outpatient department. PARTICIPANTS: Twenty women with DSM-III-R mild dementia living in the community were compared with 40 cognitively normal community-dwelling women, matched for age, who had been recruited as part of studies in elderly twins. MEASUREMENTS: Bone density at the lumbar spine and neck of femur by dual-energy X-ray absorptiometry, intact serum PTH, and 25-hydroxyvitamin D levels. MAIN RESULTS: There was no significant difference in bone density between the subjects with mild dementia and the age- and sex-matched controls. The intact PTH (mean +/- SD) in the demented subjects was 4.9 +/- 2.1 pmol/L compared with 2.9 +/- 1.7 pmol/L in the twin controls (P < .01). The mean 25-hydroxyvitamin D in the demented subjects was 61 +/- 33 nmol/L, whereas it was 90 +/- 38 nmol/L in the twin controls (P < .01). CONCLUSIONS: We conclude that there were no significant differences in the bone density of community-dwelling women with mild dementia compared with normals. However, there were significant differences in parathyroid hormone and vitamin D levels between the two groups, suggesting that there is a high prevalence of subclinical hypovitaminosis D in demented women in the community.

Absorptiometry, Photon↗

Bone mineral density and body composition in congenital adrenal hyperplasia.

The purpose of this study was to assess whether replacement doses of glucocorticoid hormones administered to patients with congenital adrenal hyperplasia (CAH) cause changes in body composition, including either generalized or regional osteoporosis. In 21 patients with 21-hydroxylase deficiency we measured height, body mass index, lean mass, fat mass, and whole body and regional bone mineral density (BMD). We measured the same parameters in 21 age- and sex-matched control patients. The CAH group (aged 8-32 yr) showed significantly reduced mean height compared with both standard data (P = 0.0015) and the control group (P = 0.009). There were no significant differences in mean body mass index between the CAH group and the standard data (P = 0.13) or the control group (P = 0.87). CAH males had significantly higher fat/lean mass ratios than control males (P = 0.005). There were no significant differences in whole body mean bone mineral apparent density values between the CAH and control groups (P = 0.39). There were, however, significant differences in whole body BMD z scores between the CAH and control groups and the reference data (P = 0.027 and P = 0.004, respectively). No significant differences were observed between the total CAH and control groups with respect to spinal bone mineral apparent density; however CAH males had significantly lower mean adjusted spinal BMD than the male controls (P = 0.02). We conclude that although replacement therapy with glucocorticoid and mineralocorticoid hormones in our group of CAH patients may not be optimal with regard to longitudinal growth, it is not deleterious in terms of general bone mineralization. It may decrease spinal BMD in CAH males. We also conclude that the relevance of Hologic reference data for BMD to an Australian population is uncertain, and there is a need for Australian standard data.

Absorptiometry, Photon↗

1,25-Dihydroxyvitamin D3-induced upregulation of the thyrotropin-releasing hormone receptor in clonal rat pituitary GH3 cells.

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) is active in primary dispersed and clonal pituitary cells where it stimulates pituitary hormone production and agonist-induced hormone release. We have studied the effect of 1,25-(OH)2D3 on thyrotropin-releasing hormone (TRH) binding in clonal rat pituitary tumour (GH3) cells. Compared with vehicle-treated cells, 1,25-(OH)2D3 (10 nmol/l) increased specific [3H]MeTRH binding by 26% at 8 h, 38% at 16 h, 35% at 24 h and reached a maximum at 48 h (90%). In dose-response experiments, specific [3H]MeTRH binding increased with 1,25-(OH)2D3 concentration and reached a maximum at 10 nmol/l. Half-maximal binding occurred at 0.5 nmol 1,25-(OH)2D3/l. The vitamin D metabolite, 25-OH D3, increased [3H]MeTRH binding but was 1000-fold less potent than 1,25-(OH)2D3. In equilibrium binding assays, treatment with 10 nmol 1,25-(OH)2D3/l for 48 h increased the maximum binding from 67.4 +/- 8.8 fmol/mg protein in vehicle-treated cells to 96.7 +/- 12.4 fmol/mg protein in treated cells. There was no difference in apparent Kd (1.08 +/- 0.10 nmol/l for 1,25-(OH)2D3-treated and 0.97 +/- 0.11 nmol/l for vehicle-treated cells). Molecular investigations revealed that 10 nmol 1,25-(OH)2D3/l for 24 h caused an 8-fold increase in TRH receptor-specific mRNA. Actinomycin D (2 micrograms/ml, 6 h) abrogated the 1,25-(OH)2D3-induced increase in [3H]MeTRH binding. Cortisol also increased [3H]MeTRH binding but showed no additivity or synergism with 1,25-(OH)2D3. TRH-stimulated prolactin release was not enhanced by 1,25-(OH)2D3. We conclude that the active vitamin D metabolite, 1,25-(OH)2D3, caused a time- and dose-dependent increase in [3H]MeTRH binding. The effect was vitamin D metabolite-specific and resulted from an upregulation of the TRH receptor. Further studies are needed to determine the functional significance of this novel finding.

Animals↗

Precise accurate mineral measurements of excised sheep bones using X-ray densitometry.

An Hologic QDR 1000-W dual energy X-ray absorptiometer (DXA) was used to make a densitometric evaluation and to optimize ex vivo scanning and analysis conditions for excised sheep bones. Articulated lumbar spines and femora, removed at autopsy from eight 1-2-year-old cross-bred merino ewes, were studied using standard lumbar spine and hip protocols (version 4.20). Spine data were analysed with the ultra-high resolution (UHR) protocol (version 4.25). Preliminary hip measurements also were made using the lumbar spine (version 4.20) and scoliosis protocols (version 4.25). Bone mineral density (BMD) precision for the total hip (n = 5) was 0.4% using version 4.20, and 0.8% using the scoliosis protocol (version 4.25) but was 1.2-3.4% for femoral sub-regions. Precision for the lumbar spine was 0.8% (version 4.20). There was considerable variation in BMD and bone mineral content (BMC) at the same site between animals. Right and left hip BMD were highly correlated (r = 0.98, P < 0.00001). Measurement variables evaluated to determine the optimal conditions included: Hologic scanning protocols, depth of water immersion of bone and dimensions of the region of interest. Accuracy was determined by ashing. Use of the scoliosis protocol (version 4.25) gave the best results for proximal femur measurement. Measured BMC decreased by 4.4% as the water depth increased from 0 to 22.5 cm. At 5 cm water, BMC accuracy was 99% for the total hip, and BMD precision values (n = 3) were 0.3% (total hip) and 0.4% (femoral neck, trochanteric region and femoral shaft). The much-improved precision was attributed to use of a positioning device and to optimizing of the depth of water immersion. Rib segments (length 2.5 cm) were measured using the ultra-high resolution protocol (version 4.25). BMC accuracy determined using 6 ribs was best (100 +/- 2%) at 5 cm water. BMD precision (n = 5) was best (0.3%) at 0 cm water depth and was 0.5% at 4.5 cm water depth. Rib sample BMC (n = 15, 4.5 cm water depth) and ash weight were highly correlated (r = 0.985, P < 0.001). It is concluded that highly precise, accurate densitometry can be performed on excised small and large sheep bones. This technique will support studies evaluating the sheep as an animal model of human osteoporosis.

Absorptiometry, Photon↗

Effects of prednisolone and deflazacort on osteocalcin metabolism in sheep.

Glucocorticoids adversely affect bone and mineral metabolism through a number of mechanisms, including inhibition of bone formation. Deflazacort is a glucocorticoid which has been reported to be relatively "bone-sparing." We compared the effects in oophorectomized sheep of deflazacort and prednisolone on the metabolism of osteocalcin (OC), a marker of osteoblast function. An [125]OC infusion method was used to measure the OC plasma clearance rate (PCR) and OC plasma production rate (PPR). Six-day intravenous infusion of deflazacort and prednisolone (in the dose range 0.007-1.00 mg/hour) induced dose-dependent decreases in OC PPR which were of a similar pattern but significantly different magnitude (P < 0.02); deflazacort demonstrated a potency about 150% that of prednisolone. Both steroids decreased plasma OC levels on a dose-related basis but at the lower doses 0.05 mg/hour (P < 0.05) and 0.013 mg/hour (P < 0.0005), deflazacort caused greater decrements. OC PCR was significantly increased only by higher doses of deflazacort (1.00 mg/hour, 0.25 mg/hour; P < 0.05). Deflazacort and prednisolone increased both postabsorptive plasma glucose and plasma calcium levels, but there were no significant differences between their effects. We conclude that plasma OC levels and OC PPR in sheep were more sensitive to the effects of deflazacort than to prednisolone. At high doses, the depressive effect of deflazacort on plasma OC levels may have been due in part to an increased OC PCR which was not evident with prednisolone treatment. However, the agents appeared to have a similar dose-dependent hyperglycemic effect, and both caused a small dose-dependent increase in plasma calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Osteoporosis: pathogenesis, diagnosis, prevention and management.

Osteoporosis has emerged as a major and increasing health problem requiring interventions at both the individual and community levels. Most cases of osteoporosis are found among women after the menopause, since menopausal status and age are key predictors of fracture risk. This review has focused particularly on osteoporosis occurring in postmenopausal women: the magnitude of the problem, how it occurs, how it is diagnosed, strategies in prevention and treatment. The diagnosis of osteoporosis and identification of individuals with heightened fracture risk due to osteopenia have been greatly facilitated by the development of dual energy X-ray absorptiometry, a simple, safe, highly precise technique for bone density measurement. Where possible, intervention strategies in osteoporosis have been related to what is known about the pathogenesis of bone loss, especially the management of modifiable risk factors. Oestrogen deficiency of any cause results in accelerated bone turnover, with an increase in the rate of net bone loss. Exogenous oestrogens can control this form of bone loss. In established osteoporosis, hormone replacement therapy can achieve clinically-significant gains in bone mass. Consideration of hormone replacement therapy is pivotal in preventive and therapeutic strategies. Issues other than osteoporosis must be taken into account when hormone replacement is considered. Attention to other modifiable risk factors, both in the lifestyle and of a medical nature, is also indicated. A number of promising agents for the treatment of established osteoporosis are described. However, available data on fracture prevention by these agents are limited. There is concern that an ideal therapy for established osteoporosis may not be achievable. Therefore, strong emphasis is placed on the need for osteoporosis prevention now and in the foreseeable future. Although much has been learnt in recent years, more research is needed in the long-term prediction of fracture risk, broadly-applicable measures to reduce the prevalence of osteoporosis, and targeted interventions for individuals at high risk.

Bone Density↗

Evaluation of dual energy X-ray absorptiometry as a method of measurement of body fat.

Two densitometers, the Hologic QDR 1000W densitometer (QDR) and the Lunar DPX densitometer (DPX), were compared with four traditional methods for the measurement of body fat: underwater weighing (UWW), skinfold thickness measurements (SKM), bioelectrical impedance analysis (BIA) and deuterium oxide dilution (D2O). Precision was assessed by conducting 10 repeated observations on one subject using QDR: the coefficient of variability (CV) was 1.8% for percentage fat, 0.6% for lean mass and 2.1% for fat mass. In 10 repeated observations on three subjects, QDR CV was greater than UWW (CV percentage fat QDR 1.3% (range 0.9-1.6%) compared with 4.8% (range 3.8-6.6%) for percentage fat UWW). Based on observations of 12 subjects, correlations of QDR and DPX with UWW for percentage fat were high: Pearson's r = 0.916, P < 0.0001 for QDR and r = 0.913, P < 0.00001 for DPX. A limits of agreement estimate showed a between-method difference of +1.3% (range -4% to +7%) for QDR compared with UWW. The DPX showed a between-method difference of +4.8% (range +2% to +9%) compared with UWW. The correlation of the two DEXAs was high (r = 0.986, P < 0.0001). Correlations between both DEXA instruments and other methods were high (for QDR: r = 0.824, P < 0.001 for SKM; r = 0.972, P < 0.0001 for BIA; r = 0.787, P < 0.002 for D2O; for DPX: r = 0.923, P < 0.00001 for SKM; r = 0.910, P < 0.00001 for BIA; r = 0.812, P < 0.001 for D2O). It was concluded that QDR and DPX measured percentage fat with greater precision than UWW as reflected by the CV and correlated with other methods. Predicted percentage fat measurements using QDR would be 3% lower than DPX, but both DEXAs predict percentage fat 1.3-4.8% higher than UWW. In addition, the DEXA technique has the unique ability to produce precise regional measurements (for each arm, each leg, the head and the trunk) of bone mineral content (BMC), fat mass (FAT), lean mass (LEAN) and percentage fat.

Absorptiometry, Photon↗

The effect of aging on intact PTH and bone density in women.

OBJECTIVE: To determine whether age-related bone loss is negatively associated with serum intact parathyroid hormone (PTH). DESIGN: Survey. SETTING: University hospital outpatient department. PARTICIPANTS: 100 community-dwelling women, age 18 to 80, recruited as a convenience sample. MEASUREMENTS: Dependent variables--bone density at the spine and femoral neck by dual-energy X-ray absorptiometry. Independent variables--age, menopausal status (binary) and intact serum PTH by Allegro immunometric assay. RESULTS: Post-menopausal women had higher serum PTH and lower bone density of spine and femoral neck than premenopausal women. Bone density at the spine decreased with age, but this effect was accounted for by menopausal state. Bone density at the femoral neck decreased with age even after adjusting for menopause. Log PTH was negatively associated with bone density at the femoral neck but not significantly at the spine. Multiple regression analysis adjusting for age and menopause showed no significant association between intact PTH and bone density at the spine or the femoral neck. CONCLUSION: Although this study confirmed the rise in intact PTH with age, there is no evidence that this is the mediator of age-related bone loss.

Absorptiometry, Photon↗

Behavioral and tissue responses to severe phosphorus depletion in cattle.

Two-year-old Aberdeen Angus heifers were depleted of phosphorus (P) by loss of phosphate in saliva from a parotid gland fistula combined with a low-P diet. The inorganic phosphate concentrations (Pi) of plasma, parotid saliva, ruminal fluid, and feces were reduced, but cerebrospinal fluid Pi was unaltered. Plasma Pi fell to less than 1.0 mM in 12 wk, and the cows displayed an avid appetite for old bones. P-deficient cows preferred old weathered bones to fresh bones until the latter had aged for approximately 1.5 yr. They did not eat blood, peritoneal fat, or meat, fresh or aged for 2-3 yr. They did not eat Na or Ca phosphate salts or bone heated to greater than 250 degrees C. P-replete cows did not take or eat bones. The behavioral effects of P deficiency were associated with failure to gain body weight and maintain condition, significant bone changes indicated by reduced bone weight and specific gravity, osteopenia indicated by radiology, evidence of reduced bone formation indicated by plasma osteocalcin levels and histology, and abnormal estrous cycles. Prolonged P deficiency was associated with increased plasma concentrations of total Ca and 1,25-dihydroxyvitamin D and reduced plasma concentrations of parathyroid hormone.

Animals↗

Culture requirements for optimal expression of 1 alpha,25-dihydroxyvitamin D3-enhanced thyrotropin secretion.

An effect of the hormone, 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] on hormone secretion by normal rat pituitary cells was investigated in vitro. Based on previous findings using GH4C1 cells, dispersed anterior pituitary cell cultures were prepared and maintained in serum-free conditions for up to 6 d. Under these circumstances, there was no effect of 1,25(OH)2D3 to alter medium or cell-associated levels of thyrotropin (TSH), prolactin (PRL), or growth hormone (GH). Cultures maintained under these conditions had lower medium and cell-associated hormone levels and lesser responses to agonists than cultures maintained in serum-supplemented medium. In the presence of 10% charcoal-treated fetal bovine serum, treatment with 10(-8) M 1,25(OH)2D3 for 24 h selectively increased TRH (10(-10) to 10(-7) M)-induced TSH secretion (P less than 0.001), with maximal enhancement observed at 10(-9) M TSH-releasing hormone (TRH). Enhancement of TSH secretion by 1,25(OH)2D3 was detected after 15 min exposure to TRH. There was no effect on agonist-induced PRL or GH secretion or on cell-associated hormone levels. The effect was evident after 24 h treatment with 1,25(OH)2D3, and decreased thereafter. Several other steroid hormones had no effect on 10(-9) M TRH-induced TSH secretion. These data contrast with the effect of 1,25(OH)2D3 in GH cells. They suggest that 1,25(OH)2D3 may act selectively in the normal pituitary to modulate TSH secretion.

Animals↗

The effect of uninephrectomy on osteocalcin metabolism in sheep: a direct evaluation of renal osteocalcin clearance.

Indirect evidence has suggested that the kidney is a major organ of clearance for osteocalcin, a circulating marker of osteoblast function. The objectives of the present study were (1) to confirm the role of the kidney in osteocalcin clearance (2) to quantify the contribution of extrarenal sites and (3) to investigate the renal mechanism(s) of osteocalcin clearance. Plasma osteocalcin levels, osteocalcin plasma clearance rate (PCR) and plasma production rate (PPR) were determined in oophorectomized (OX) and uninephrectomized oophorectomized (UOX) sheep. The osteocalcin renal extraction efficiency (REE) and the effective renal plasma flow (ERPF) were measured, and the osteocalcin renal clearance rate (RCR) was calculated. The osteocalcin PCR was reduced significantly in UOX compared with OX sheep (2.0 +/- 0.1 (n = 9) vs 2.5 +/- 0.1 litres/h (n = 44); P less than 0.0005). In UOX sheep with plasma creatinine levels less than or equal to 130 mumol/l, the osteocalcin REE was 9 +/- 1.3% and the osteocalcin RCR was 50-91% of osteocalcin PCR (n = 4). In UOX sheep with plasma creatinine levels in the range 100-440 mumol/l, there was a linear relationship between osteocalcin PCR and ERPF; the osteocalcin RCR was related to the osteocalcin PCR (RCR = 0.9 x PCR - 0.50). Intravenous infusion of the synthetic glucocorticoid triamcinolone acetonide (TA) in UOX sheep led to marked decrements in plasma osteocalcin levels and the osteocalcin PPR, and a significant increase in the osteocalcin PCR. These changes were accompanied by a 44% increase in ERPF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antacid-induced phosphate depletion syndrome presenting as nephrolithiasis.

A 29-year-old insulin-dependent diabetic woman developed phosphate depletion, nephrolithiasis and bilateral ureteric obstruction due to antacid abuse. Unlike previous descriptions of chronic phosphate depletion, myalgia, weakness and bone pain were absent. Biochemical features included hypophosphataemia, hypercalciuria, hypophosphaturia, elevated plasma, 1,25-dihydroxyvitamin D and low plasma intact parathyroid hormone. These abnormalities were corrected when antacid ingestion was reduced and phosphate intake supplemented. We propose that phosphate depletion secondary to antacid abuse caused 1 alpha-hydroxylase activation and elevation of the plasma 1,25-dihydroxyvitamin D level, leading to marked hypercalciuria. Once diagnosed, antacid abuse is a readily reversible cause of hypercalciuria and renal stones. Moreover, antacid-induced phosphate depletion may present with nephrolithiasis in the absence of musculoskeletal symptoms. This report is intended to draw attention to this important cause of renal stone disease.

Adult↗

The in vitro effect of 1 alpha,25-dihydroxyvitamin D3 on insulin production by neonatal rat islets.

The in vitro effect of 1 alpha,25-dihydroxyvitamin D3 on the function of beta cells of the endocrine pancreas was investigated. Neonatal islets maintained in serum-free medium, or medium supplemented with 0.5% fetal bovine serum achieved a 2.5-fold increase in medium insulin levels in response to 10(8) M 1 alpha,25-dihydroxyvitamin D3 (P less than 0.001). The effect of 1,25-dihydroxyvitamin D3 required at least 96 h treatment to become evident and was similar at medium glucose concentrations of 10 and 20 mM. Cell-associated insulin was increased in 1 alpha,25-dihydroxyvitamin D3-treated cultures maintained in 0.5% serum. These data suggest that 1 alpha,25-dihydroxyvitamin D3 may have a direct effect in the beta cell.

Animals↗

Hormonal regulation of osteocalcin plasma production and clearance in sheep.

The plasma osteocalcin (OC) concentration correlates with histological parameters of bone formation and has been used as an index of osteoblast activity. Although the rate of OC synthesis is likely to be a major determinant of the plasma OC level, the contribution of other processes, for example, OC plasma clearance, should be evaluated if changes in the plasma OC concentration are to be interpreted meaningfully. We have treated oophorectomized sheep with 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and glucocorticoids to alter the plasma OC concentration and used an 125I-OC infusion method to measure changes in the OC plasma clearance (PCR) and to calculate production (PPR) rates. 1,25-(OH)2D3 (8 micrograms/day by iv injection) increased plasma OC levels from 15.8 +/- 2.1 to 52.7 +/- 5.3 ng/ml (n = 10; P less than 0.0005) and the OC PPR from 0.9 +/- 0.08 to 2.6 +/- 0.17 mg/day (n = 5, P less than 0.0005). There was no effect on the OC PCR. Both triamcinolone acetonide (TA) and cortisol, administered by iv infusion, decreased the plasma OC concentration to less than 4 ng/ml and the OC PPR to less than 0.4 mg/day when infused in the doses 0.05-1.0 mg/h (TA) and 2.0 mg/h (cortisol). TA (0.05 mg/h) decreased plasma OC to an undetectable level within 24 h. The effect of cortisol infusion on the plasma OC level and the OC PPR was dose dependent in the range 0.2-2.0 mg/h. TA, infused at the rates of 0.25 and 1.0 mg/h, increased the OC PCR from 3.0 +/- 0.10 to 4.0 liters/h (P less than 0.005; n = 4) and from 2.6 +/- 0.10 to 3.9 +/- 0.10 liters/h (P less than 0.01; n = 3), respectively. It is concluded that the OC PPR and the plasma OC concentration in sheep are responsive to treatment with 1,25-(OH)2D3 and glucocorticoids. Although the changes in plasma OC concentration were attributable largely to effects on OC production, high infusion rates of the glucocorticoid TA led to a highly significant increase in OC plasma clearance. These findings suggest that alterations in OC clearance may contribute to the changes in plasma OC levels seen in some disease states, for example, glucocorticoid excess.

Alkaline Phosphatase↗

Osteocalcin as an index of osteoblast function during and after ovine pregnancy.

Fetal and neonatal calcium requirements impose heavy demands on maternal bone and mineral homeostasis. The functional response of maternal osteoblasts to this stress is poorly understood. Therefore, plasma osteocalcin (OC) levels were measured by homologous RIA in age-matched nonpregnant, pregnant, and postpartum ewes to evaluate osteoblast function. In pregnant ewes from day 35 of gestation to term, the plasma OC level was suppressed to 8.2 +/- 0.5 micrograms/liter (mean +/- SEM; n = 36) compared with age-matched nonpregnant ewes (18.3 +/- 1.1 micrograms/liter; n = 39; P less than 0.0005). Plasma OC rose to the nonpregnant value by day 20 postpartum and was elevated above this level for the following 40 days (e.g. 44.0 +/- 5.0 micrograms/liter at 48-53 days; P less than 0.0005). The timing of changes in plasma OC levels and weaning did not correlate. The validity of plasma OC measurement as a marker of osteoblast function was assessed by determining the OC plasma production and clearance rates using an [125I]ovine OC infusion method. The OC plasma production rates in matched controls (n = 6), pregnant (n = 9), and 48-53-day postpartum sheep (n = 7) were 1.5 +/- 0.2, 0.5 +/- 0.04 (P less than 0.001 vs. control), and 3.6 +/- 0.6 mg/day (P less than 0.005 vs. pregnant sheep), respectively. In one ewe studied longitudinally, the OC plasma production rate increased by 15 days after parturition and achieved a 10-fold elevation at 49 days postpartum. The OC plasma clearance rate (3.3 +/- 0.3 liters/h) was the same in control, pregnant, and postpartum ewes. It is concluded that 1) changes in plasma OC levels during and after ovine pregnancy reflected changes in OC production, 2) plasma OC measurements are likely to be a useful index of osteoblast function in pregnancy, and 3) osteoblast function appears to be depressed during ovine pregnancy and enhanced markedly in the interval 20-60 days postpartum. The relationship between osteoblast function, as indicated by OC production, and bone formation remains to be clarified.

Aging↗

Vitamin D-enhanced thyrotrophin release from rat pituitary cells: effects of Ca2+, dihydropyridines and ionomycin.

Vitamin D may regulate pituitary function, as there are selective effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on gene expression in clonal pituitary tumour cells, and on TRH-induced TSH release in normal rat pituitary cells in vitro. The role of Ca2+ in 1,25-(OH)2D3-enhanced TSH release from primary rat pituitary cell cultures was investigated. Pretreatment with 10 nmol 1,25-(OH)2D3/l for 24 h augmented KCl (3-60 mmol/l)-induced TSH release over 1 h at all KCl concentrations greater than 7.5 mmol/l (P less than 0.001), with a 76% enhancement of TSH release induced by 30 mmol KCl/l (P less than 0.001). The Ca2+ channel antagonist nifedipine (10 nmol/l-10 mumol/l) caused a concentration-dependent inhibition of KCl (60 mmol/l)-induced TSH secretion. Pretreatment with 1,25-(OH)2D3 enhanced KCl-induced release at all concentrations of nifedipine (P less than 0.001). The Ca2+ selective divalent cation ionophore ionomycin (1 nmol/l-1 mumol/l), and the Ca2+ channel agonist BAY K 8644 (10 nmol/l-1 mumol/l) increased prolactin secretion but did not increase TSH release, and 1,25-(OH)2D3 had no effect. At an extracellular Ca2+ concentration of less than 500 nmol/l, TRH-induced TSH release was observed only after treatment with 1,25-(OH)2D3 (P less than 0.01). As the extracellular Ca2+ concentration was increased, greater increments of TRH-induced TSH release were observed following pretreatment with 1,25-(OH)2D3 (P less than 0.01). However, the effect of 1,25-(OH)2D3 in the thyrotroph was independent of the pretreatment extracellular Ca2+ concentration. We have shown that 1,25-(OH)2D3 acts selectively on the thyrotroph to enhance in-vitro responsiveness to TRH and KCl. These data suggest that the action of 1,25-(OH)2D3 in the thyrotroph is to enhance intracellular signal transduction. They further support a permissive or regulatory role of vitamin D in the normal pituitary gland.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗