Biomedical subjects

V Coxam

Publications and source records attributed to V Coxam.

At least 37 records · Page 2Linked to original sources

PubMed1999

Endurance training and bone metabolism in middle-aged rats.

This study was performed to observe the influence of moderate treadmill running on bone of middle-aged male rats. Seventy 15-month-old Wistar rats were used. Ten initial controls (IC) were killed on day 0. Among the 60 others, three groups of ten exercised rats (E) run 1 h/day, 6 days/week at 60% of their maximum aerobic capacity. On days 30, 60 and 90 of the training period, 20 rats, ten E and ten R (resting animals), were killed. Femoral failure stress never varied and was never different in E and R during the experiment. On day 90 whole body mineral content and mineral density were higher in E than R. Simultaneously, total, diaphyseal and metaphyseal femoral densities were lower in R than IC or than in E. No difference was observed between IC and E. In resting rats, urinary deoxypyridinoline excretion (a marker of bone resorption) increased between days 0 and 90, while it did not change in runners. These results indicate that in middle-aged rats, moderate running prevents decrease in bone mineral density, probably by inhibiting bone resorption.

Aging↗

PubMed1999

Treadmill running starting 3 months after orchidectomy restores femoral bone mass in rats.

The present study was designed to provide data on the effects on femoral bone of endurance training starting only 3 months after orchidectomy in rats. A total of 70 Wistar male rats were used at 8 weeks of age. On day 0 of the experiment, 10 rats were killed by cervical dislocation to be used as first controls. Among the 60 other animals, half was surgically castrated (CX) or sham operated (SH). On day 90, 10 CX and 10 SH were killed and used as intermediary controls (ICX and ISH). Among the other 20 CX and 20 SH, 10 within each group (CXE, SHE) were selected for treadmill running (60% maximal oxygen uptake, 1 h x day(-1), 5 days x week(-1) for 12 weeks). The 20 other rats were used as sedentary controls (CXR, SHR) and killed (as runners) on day 180. On day 90 femoral bone density (BMD) and mineral content (BMC) were lower in ICX than in ISH. On day 180 total femoral BMD was lower in CXR than in CXE. Simultaneously metaphyseal femoral BMD was lower in CXR than in CXE, SHR or SHE. Furthermore, at that time, no significant difference concerning BMD and BMC was observed between SHR and CXE. This would indicate that treadmill running starting only 3 months after orchidectomy is able to restore BMD and BMC to control values, mainly by inhibiting bone resorption (as shown by decreased urinary deoxypyridinoline excretion in CXE) without decreasing osteoblastic activity (evaluated by plasma osteocalcin concentration).

Amino Acids↗

PubMed1999

Does endurance running before orchidectomy prevent osteopenia in rats?

This experiment was performed to study the effects on femoral bone of endurance training performed during the 3 months before orchidectomy in rats which were then killed 90 days later. A total of 70 male Wistar rats were used at 8 weeks old. One day 0 of the experiment, 10 rats were killed by cervical dislocation and used as first controls. Among the 60 others, 30 were selected for treadmill running (60% maximal oxygen uptake, 1 h x day(-1), 6 days x week(-1) for 90 days). The 30 other rats remained at rest. On day 90, 10 exercised (IE) and resting (IR) rats were killed and used as intermediary controls. Among the 20 other animals of each group, 10 were surgically castrated (CXE, CXR) or 10 sham-operated (SHE, SHR) and killed on day 180. On day 90 femoral failure load (three-point bending test) was greater in IE than in IR. Simultaneously, the deoxypyridinolinuria was lower in IE than in IR. On day 180, femoral bones were thinner in CXR than in CXE. The lowest values for trabecular bone are in the distal femoral metaphysis were measured in CXE and CXR rats, but the value measured in CXE was no different from that measured in SHR. Simultaneously total femoral bone density was lower in CXR than in SHE, while no difference concerning femoral metaphyseal density was observed between CXE and SHR. These results confirmed that endurance running increased femoral bone growth and modelling and femoral trabecular area, and thereby peak bone mass, in 8-month-old male rats. In resting animals, castrated after the training period, androgen deficiency decreased femoral density, mineral content and trabecular area. This decrease was not observed in castrated but previously exercised rats. Thus, by increasing peak bone mass, it was considered that endurance training may have a preventive effect against orchidectomy-induced bone loss.

Absorptiometry, Photon↗

PubMed1999

Peripheral injection of growth hormone stimulates protein intake in aged male and female Lou rats.

It is well established that growth hormone (GH) induces growth rate and food efficiency and stimulates protein accretion in young mammals. Senescence is characterized by metabolic and hormonal disorders, particularly a decrease in protein turnover, which could be correlated to a decrease in GH and insulin-like growth factor I (IGF-I) secretion. We have shown that body weight, protein intake, and IGF-I plasma levels are greatly decreased with aging in Lou/C rats, particularly in males. In order to specify the GH effect on protein intake during aging, males and females (6, 19, and 24 mo) placed on a self-selection regimen were injected daily with a physiological dose of human GH (0.023 mg/rat sc). No GH effect on caloric intake was observed. Nevertheless, GH treatment stimulated body weight in older rats. It also increased protein intake in females and older males (19-24 mo). This stimulating effect was positively correlated with the degree of weight loss in senescent rats, suggesting that the decrease in protein intake observed with aging could be a marker of senescence.

Aging↗

PubMed1999

Influence of age and hormonal treatment on intestinal absorption of magnesium in ovariectomised rats.

This study was designed to assess the effect of age, ovariectomy and estrogen treatment on the absorption and the balance of Mg in the rat. Three groups of fifteen 6- (mature), 12- (old), and 30-month-old female rats (senescent), fed a diet containing 1.5 g of Mg/kg were used in the present study. Within each group, 10 rats were surgically ovariectomized (OVX). From day 2 until day 60 after OVX, they were s.c. injected with either solvant or 17 beta-estradiol (E: 10 mg/kg bw/48 h, n = 5). Five other rats were sham operated (SH, n = 5) and received solvent alone. Animals were pair fed 6 g/100 g bw/day and distilled water was available ad libitum. Food intake, urine and feces from each individual rat were measured 1 day per week, during the last 5 weeks. The results clearly showed that apparent Mg absorption (per cent) was not significantly altered with aging. Moreover, whatever the age, neither OVX nor E treatment had any significant effect on Mg apparent absorption.

Age Factors↗

PubMed1998

Influence of aging on cortical and trabecular bone response to estradiol treatment in ovariectomized rats.

Three groups (n = 15/group) of 6-, 12- and 30-month-old (mature, old and senescent animals, respectively) female Wistar rats on a diet (6 g/100 g BW/ day) containing 0.8% calcium and 0.8% inorganic phosphorus were studied. Within each group, 10 rats were ovariectomized surgically and 5 injected s.c. with 17 beta-estradiol (E rats, 10 micrograms/kg BW/48 h) and 5 with solvent alone (OVX rats) from day 2 until day 60 after ovariectomy. Five other rats were sham-operated (SH rats) and received solvent only. All rats were killed by exsanguination 60 days after ovariectomy. Neither ovariectomy nor estradiol treatment had a significant effect upon tibial mechanical properties in 6-, 12- and 30-month-old animals. Bone mineral density (BMD) and bone mineral content (BMC) of the distal femur and BMC of the whole femur were decreased by ovariectomy in 6- and 12-month-old rats, but were not different in the SH and E groups. In senescent animals, in which the lowest BMD and BMC were measured, estradiol treatment was more effective in increasing these parameters than in adult and old rats. Image analysis of the distal femoral diaphysis showed that estradiol treatment prevented trabecular bone loss induced by senescence and/or ovariectomy. In each group, urinary deoxypyridinoline excretion and plasma osteocalcin concentration were higher in the OVX animals than in the controls, consistent with increased bone turnover in the estrogen-deficient state. Both biochemical turnover markers were reduced in the estrogen-treated groups. These results indicate that 17 beta-estradiol is particularly effective at preventing high-turnover-induced osteopenia in 30-month-old animals.

Aging↗

PubMed1998

[Calcitonin and stanniocalcin. Particular aspects of the endocrine regulation of phospho-calcium metabolism in mammals and fish].

The hypocalcemic and hypophosphatemic peptide calcitonin (CT) is secreted by mammalain thyroid parafollicular cells and fish ultimobranchial body. Over a dozen species of CTs have been cloned and/or sequenced. They can be separated into three classes based on structural and biological similarities: teleost/avian, artiodactyl, and human/rat. In mammals, CT exerts its anti-hypercalcemic and hypophosphatemic effects by inhibiting osteoclastic bone resorption and renal tubular phosphate reabsorption, respectively. CT receptors (CTRs) are members of a subfamily of seven-transmembrane domain, G protein-coupled receptors that include those for several other peptide hormones. Basic amino acid substitutions within the CT molecule enhance potency, probably by conferring a helical structure to the peptide. This might explain the enhanced potency of fish CTs for mammalian CTRs. The presence and secretion of salmon CT-like immunoreactive material have been described in both the murine and human central nervous systems, which possess CTRs. These findings are consistent with a role for this peptide acting as a neurotransmitter in mammals. Stanniocalcin (STC) is another hypocalcemic hormone originally identified in fish. In fish STC exerts its anti-hypercalcemic effect by regulating calcium and phosphate transports by the gills, intestine and kidney. Although fish ultimobranchial cells are much less responsive to the secretagogic effects of Ca2+ than mammalian parafollicular cells, the secretion of both CT and STC are positively regulated by extracellular calcium. STC has also been recently identified in humans and rats. It is released by some renal tubular cells and might play a role in the regulation of phosphate metabolism. Nevertheless, the true physiologic roles for CT in fish and STC in mammals, respectively, remain unknown.

Animals↗

PubMed1997

Influence of ovariectomy and estradiol treatment on calcium homeostasis during aging in rats.

Study was carried out an Wistar female rats to evaluate the consequences of ovariectomy and 17 beta-estradiol substitutive treatment during aging on bone. Ca metabolism and calciotropic hormones. Three groups of fifteen rats, mature, old and senescent (4-, 10-, and 28 month-old) female were fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi, Within each group, 10 rats were surgically ovariectomized (OVX). From day 1 until day 60 after OVX, they were subcutaneously injected with either 17 beta-estradiol (E: 10 micrograms/kg BW/48 h; n = 5) or with solvent alone (OVX; n = 5). Five other rats were sham operated (SH) and received solvent alone. Animals were put in balance 1 day per week to determine Ca and Pi intestinal apparent absorption and urinary pyridinium cross-links excretion was measured by HPLC. All rats were killed by exsanguination 60 days after OVX. Plasma was collected for measurement of intact parathyroid hormone (PTH), calcitonin (CT), insulin-like growth factor-1 (IGF-1), Ca and Pi. The success of OVX was confirmed at necropsy by observation of marked atrophy of the uterine horns. The right femur was collected, cleaned from adjacent tissue and used for mineral analysis. Despite correct matching for feeding, BW was significantly larger in 6 and 12 month-old OVX rats. OVX and 17 beta-estradiol had no significant effect upon plasma Ca, Pi and CT concentrations. Aging is associated with increased circulating PTH levels (pg/ml) (SH-6 months: 50.8 +/- 12.6; 12 months: 219.1 +/- 34.9; 30 months: 158.7 +/- 23.5; P < 0.05). Urinary and fecal Ca and Pi excretion in senescent animals were higher than in adult or old rats, thus resulting in a drastic fall in both intestinal apparent absorption and retention of Ca and Pi in 30 month-old animals. In each group, urinary pyridinium cross-links excretion and plasma osteocalcin concentration were higher in the OVX animals than in the controls, consistent with increased bone turnover in the estrogen deficient state. Both biochemical turnover markers were reduced in the estrogen-treated groups. In the same way, OVX increased and estrogen decreased the plasma IGF-1 levels. We conclude that 17 beta-estradiol prevents high turnover-induced osteopenia even in 30 month-old rats.

Aging↗

PubMed1997

Influence of treadmill running on femoral bone in young orchidectomized rats.

Forty 6-wk-old male Wistar rats weighing 308 +/- 24 g were divided into two groups. On day 0, the 20 animals in one group were surgically castrated and the other group was sham operated. Within each group, 10 rats were selected for treadmill running (60% maximal O2 consumption, 1 h/day, 6 days/wk for 15 wk). The 20 sedentary rats were used as controls. At the time the rats were killed (day 105), running had no significant effect on femoral mechanical properties either in castrated or in sham-operated rats. Femoral bone density was lower in orchidectomized than in sham-operated rats. Nevertheless, it was higher in exercised than in sedentary rats. Femoral Ca content paralleled changes in bone density. Treadmill running had no significant effect on plasma osteocalcin concentration but inhibited the increase in urinary deoxypyridinoline excretion observed in castrated rats. Image analysis (measured at the distal femoral diaphysis) revealed that these effects mainly resulted from decreased trabecular bone resorption in castrated exercised rats.

Amino Acids↗

PubMed1997

Influence of sex steroids on development of cultured fetal rat metatarsal bones.

The effects of 17 beta-estradiol (E), dihydrotestosterone (D, a non aromatisable androgen), and progesterone (P) on osteogenesis were studied on fetal rat cartilaginous anlagues cultivated in vitro. The three medial metatarsal rudiments were harvested at day 19 of gestation and grown in 1% BSA MEM medium (MO 643, Sigma) without serum nor antibiotics. After a 18h preincubation period, hormones were added for 8 days. Paired controls were incubated in the same volume of medium. The length, the metacarpal thickness and the size of the mineralized zone were measured every day, using a calibrated eyepiece (magnification X 40). DNA and protein synthesis, cartilage metabolism and mineralization were evaluated by monitoring the incorporation of 3H-Thymidine, 3H-Proline, 35S and 45Ca into anlagues for the last three hours of incubation, respectively. The dose/response effect of each steroid was studied at the concentrations of 10(-4) M, 10(-6) M, 10(-7) M and 10(-9) M. No difference was observed between male and female fetuses. A significant positive effect on total length (% of length measured at harvesting day) was observed with the 10(-7) M dose of E (163% +/- 2 vs 148% +/- 4 in controls) or D (158% +/- 3). Endochondral growth was not modified by P treatment. The effect of the three steroids (given at a dose of 10(-7) M) alone or as combinations (E, D, P, EP, ED, PD, EPD) confirmed the positive effect of E on endochondral growth and, to a lesser extend, of D and the association ED. Nevertheless, D had a better effect than E on endomembranous growth. On the contrary, P did not affect growth neither administrated alone nor in combination with E or D, while a positive effect of P on mineralization was demonstrated. The treatment associating the three steroids slowed down all the parameters concerning growth but strongly stimulated calcification.

Androgens↗

PubMed1996

Influence of ovariectomy on bone metabolism in very old rats.

Twenty-five 30-month-old Lou rats fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi were divided into five groups. Four groups were surgically ovariectomized. From day 2 until day 29 after ovariectomy, they were S.C. injected either with 17 beta estradiol (E2; 10 micrograms/kg BW/48 hours) or progesterone (P; 140 micrograms/kg BW/48 hours), or 17 beta estradiol + progesterone (E2P) at the same doses, or solvent alone (OVX). The fifth group was sham operated (SH) and injected with solvent. Urine was collected in metabolic cages from day 24 to 29 after ovx, and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excretion (markers of bone resorption) was measured by HPLC. All animals were killed 30 days after ovariectomy. Serum was then collected for measurement of osteocalcin (OC), alkaline phosphatase (ALP), parathyroid hormone (PTH), and calcitonin (CT). At necropsy, the success of ovariectomy was checked by marked atrophy of the uterine horns. Left and right femur were harvested for densitometric and mineral analysis, respectively. Ovariectomy had no significant effect upon plasma calcium and PTH concentrations. E2 or E2P treatment significantly increased plasma PTH and calcitonin concentrations. Plasma OC concentrations and ALP were not different in any of the groups. In contrast, urinary excretion of PYD and DPD was higher in OVX than in SH rats. Bone mineral density (BMD) of the distal femur was decreased by OVX, but was not different in the E2P and SH groups. A similar pattern was observed for the mineral or Ca content of whole femur. Thus, OVX decreased BMD and bone mineral content (BMC) in very old female rats. Plasma OC concentration and ALP activity failed to demonstrate any significant effect of OVX, whereas PYD and DPD were elevated. These results suggest that bone resorption is increased in OVX rats, even when supplemented with E2 or P alone. However, no significant difference was observed between SH and OVX rats treated with supplementation of both E2 and P. Thus, in very old rats, a combination of E2 and P is much more effective than E2 or P alone to prevent bone loss following ovariectomy.

Aging↗

PubMed1996

Effects of dihydrotestosterone alone and combined with estrogen on bone mineral density, bone growth, and formation rates in ovariectomized rats.

Androgens are associated with the greater skeletal mass and size in men compared with women and have been used as anabolic agents promoting skeletal growth and mineral accretion in both sexes, but specific effects on growth and bone formation in the female skeleton are not well understood. The effects of 5 alpha-dihydrotestosterone (DHT) alone, and in combination with 17 beta-estradiol on bone and bone growth were studied in female ovariectomized (OVX) rats with established osteopenia. Eight weeks after OVX, rats were given 0.1 mg 17 beta-estradiol and/or 2.5 mg or 10 mg DHT administered by controlled-release pellets for 2 months. Body weights decreased with estrogen treatment but increased with DHT. Bone mineral density increased with the highest dose of DHT relative to OVX controls and the estrogen treated group. Dry and ashed bone weights and ash/dry weight ratios increased in the estrogen and DHT treated animals compared to the baseline OVX controls. Total bone calcium was greater with DHT and estrogen combined with DHT. The percent of calcium in the ash increased in all DHT treated groups. When normalized to final body weight, the total femur calcium content was significantly increased in the estrogen and estrogen with DHT groups, but not in the DHT groups compared with the baseline OVX and OVX control groups. The periosteal bone formation rates were increased with the high dose DHT alone and combined with estrogen. OVX rats had increased endochondral bone elongation rates relative to controls but this was decreased with estrogen treatment. DHT combined with estrogen increased endochondral growth rates relative to the estrogen treated group. Trabecular bone volume was decreased in all OVX groups relative to the base line group, but there were no significant effects observed with any treatments. Cancellous bone formation rates were suppressed with estrogen treatment but were partially reversed when combined with DHT. DHT treatments also increased most cancellous bone formation indices over OVX controls. While estrogen is known to preserve skeletal mass by reducing bone turnover, DHT increased skeletal mass by promoting bone growth and formation with concomitant increases in total body mass. DHT had greater effects on cortical bone and partially mitigated the suppressive effects of estrogen on bone growth and formation in the female skeleton.

Analysis of Variance↗

PubMed1996

Water restriction and bone metabolism in camels.

'Krafft disease', occurring in camels living in the very arid areas of North Africa, is characterized by spontaneous fractures of costal and/or appendicular bones. To better understand the mechanisms of this, we studied the influence of water restriction on plasma and urinary markers of bone metabolism in camels. Eight 2-year-old nonpregnant, nonlactating camels were studied at the research station of Laâyoune (Morocco). After a 10 day period of daily watering, five animals were watered only every 10th day over a 50 day period, then again watered daily for a final 10 day period (rehydration). The three control animals were watered daily throughout the whole experimental period (70 days). Each camel was fed a ration of straw, luceme hay and barley, resulting in a daily intake of 25 g calcium and 11 g phosphorus. Water restriction induced a decrease in daily urinary volume and an increase in plasma osmolality. These symptoms of dehydration were not associated with any significant change either in the markers of osteoblastic activity (plasma alkaline phosphatase activity and osteocalcine concentration) or in the markers of bone resorption (urinary excretion of calcium, hydroxyproline pyridinoline and deoxypyridinoline). Thus, in well-fed camels, water restriction did not affect bone metabolism. However, no conclusions were possible regarding the influence of dehydration or calcium and/or phosphorus deficiency in the etiology of 'Kraft disease'.

Alkaline Phosphatase↗

PubMed1996

Ontogenesis of IGF regulation of longitudinal bone growth in rat metatarsal rudiments cultured in serum-free medium.

The aim of this study was to compare the effect of two cytokines, IGF-I and IGF-II on skeletal development in the rat. The three medial metatarsal rudiments were dissected out from fetuses at days 19, 20 or 21 of gestation and from newborns at days 1, 3, 6 and 9 after birth, then grown in serum-free MEM medium at 37 degrees C and 5% CO2 in air. From day 19 of gestation to the end of experiment, longitudinal bone growth (mm) was significantly increased by IGF-I (2.975 +/- 0.050) and IGF-II (2.530 +/- 0.062), compared to controls (2.188 +/- 0.060). In the same way, the width (mm) at the last experimental day was 0.360 +/- 0.010 in IGF-I- and 0.327 +/- 0.008 in IGF-II-treated bones, respectively (vs 0.313 +/- 0.012 in controls). Mineralization was also stimulated under both growth factors (length of the calcified diaphysis (mm): 0.691 +/- 0.019 in IGF-I- and 0.446 +/- 0.017 in IGF-II-treated bones; vs 0.383 +/- 0.024 in controls). IGF-I and IGF-II (but to a lesser extent) stimulation was due to an increased DNA synthesis (3H-thymidine uptake) as well as protein anabolism (incorporated proline). In addition, cartilage activity (35S captation) and mineralization (45Ca fixed) were involved in the action of these cytokines. An age dependency of bone response to IGFs was pointed out, the effect being higher during the fetal period than after birth. In conclusion, our results raise the possibility that IGF-II, as well as IGF-I, is involved in the control of osteogenesis.

Animals↗

PubMed1995

[Relation between the parathyroid glands and arterial pressure: is there a parathyroid hypertensive factor?].

Parathyroid hypertensive factor (PHF) is a newly discovered circulating factor that has been implicated in some forms of hypertension. Such an involvement has been established in several animal models and in hypertensive patients. PHF originates from the parathyroid glands. This explains why hypertensive individuals often have high levels of circulating parathyroid hormone (PTH), which is itself hypotensive. This would reflect the activity of the parathyroid glands, which would produce PHF concomitantly with PTH. The mechanism of action of PHF involves an increase in calcium-channel activity in vascular smooth muscle cells. The opening of these channels would lead to increase calcium entry into these cells, resulting in increased sensitivity to other vasoconstrictors. PHF level explains why a high calcium diet may be effective in lowering blood pressure in patients who respond to calcium-channels blockers: dietary calcium might inhibit the production of PHF (and PTH), whereas calcium-channels blockers would inhibit PHF at its target site.

Biological Factors↗

PubMed1995

Regulation of urinary phosphate excretion in camels.

Urinary inorganic phosphorus (P) excretion was measured in 16 adult female non-pregnant, non-lactating daily watered camels. They were randomly divided into four groups of four animals. Groups 1, 2, and received either an i.v. infusion of phosphate or synthetic human parathyroid hormone (PTH) or PTH-related peptide (PTHrP), respectively. The fourth group was used as a control. Intravenous P loading induced a significant increase in phosphatemia and in P renal clearance. Both PTH and PTHrP increased calcemia and decreased phosphatemia. They had no significant effect on urinary calcium excretion, but they increased P renal clearance and phosphaturia. Thus, the regulation of urinary P excretion in normally watered camels looks similar to that already described in other ruminants.

Animals↗

PubMed1995

EB 1089, a calcitriol analogue, decreases fetal calcium content when injected into pregnant rats.

EB 1089 is a calcitriol analogue with low calcaemic activity, which inhibits parathyroid hormone-related peptide (PTHrP) secretion in rats implanted with the Leydig cell tumour H-500. We have studied its effect on maternal and fetal plasma PTHrP concentrations and on fetal calcium and phosphorus contents in rats. Three groups of six pregnant rats were injected I.P. daily with EB 1089 (0.10, 0.25 and 0.50 microgram kg-1 in groups 1, 2 and 3, respectively, from day 12 to day 20 of gestation). The control group received an equal volume of solvent alone. On day 21 of gestation the animals were anaesthetized with chloral hydrate and blood samples were taken. Fetuses were collected, weighed and ashed for Ca and P measurements. PTHrP concentrations were measured by radioimmunoassay (RIA) in maternal and fetal plasma. Calcium content (mg (g fetal wt)-1; mean +/- S.E.M.) in control fetuses was not different from that measured in fetuses from dams given the lowest dose of EB 1089, but was higher than that in fetuses from rats injected with EB 1089 at 0.25 microgram kg-1 (1.18 +/- 0.20; P < 0.05) or 0.50 microgram kg-1 (1.08 +/- 0.29; P < 0.05). There was no difference in fetal P content between any of the groups of rats. The PTHrP concentration (pg equivalents human PTHrP(1-34) fragment ml-1) in maternal plasma from control rats (1.70 +/- 0.50) was not different from that in maternal plasma of rats given the lowest dose of EB 1089 (1.44 +/- 0.63).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Insulin-like growth factor 1 and parathyroid hormone effects on the growth of fetal rat metatarsal bones cultured in serum-free medium.

Insulin-like growth factor 1 (IGF-1) has roles in bone growth, and parathyroid hormone (PTH) is suspected of having effects on bone, perhaps mediated by IGF-1. The purpose of this study was to determine the individual and combined effect of PTH and IGF-1 on fetal long bone metabolism. Three medial metatarsal bones were dissected from Sprague-Dawley rat fetuses harvested at the 19th day of gestation, then grown in serum-free MEM. IGF-1 (group II) or PTH (group PP) were added at the dose of 100 ng/ml for 8 days. In a third group (PI), bones were preincubated for 4 days with PTH followed by a 4-day incubation with IGF-1. Both hormones stimulated endochondral (longitudinal) growth, the highest effect was observed with IGF-1 (II: 3.11 +/- 0.06 vs. 2.16 +/- 0.08 mm in controls). The length elicited by the PI treatment ranged between those measured with IGF-1 (II) and PTH (PP) given alone (PI: 2.80 +/- 0.04 mm; PP: 2.57 +/- 0.06 mm). In addition, both hormones enhanced periosteal growth (endomembranous ossification), as measured by the width of bones (II: 0.39 +/- 0.02 mm; PP: 0.34 +/- 0.02 mm; PI: 0.38 +/- 0.02 vs. 0.29 +/- 0.01 mm in controls). On the other hand, IGF-1 but not PTH caused a significant increase in 35S incorporation (as an indicator of sulfated proteoglycan synthesis in cartilage (percent of incorporating activity; II: 0.18 +/- 0.04%; PI: 0.09 +/- 0.01 vs. 0.03 +/- 0.01% in controls). Nevertheless, both IGF-1 and PTH enhanced osteoblastic activity as shown by increased alkaline phosphatase activity in treated bones (II: 1.18 +/- 0.00 mumol/bone; PP: 0.50 +/- 0.00 vs. 0.28 +/- 0.00 mumol/bone). In conclusion, IGF-1 had the greatest effects on growth in bone length (endochondral osteogenesis) and bone width (intramembranous osteogenesis) and appeared to stimulate both chondrogenesis and osteogenesis. It also increased growth but appeared to have greater effects on osteogenesis than on chondrogenesis. Pretreatment with IGF-1 followed by PTH produced effects that were intermediate between the groups treated with IGF-1 and PTH alone.

Animals↗