Bone Growth Rate Research Articles

Heterochronic patterns in primate evolution: evidence from endochondral ossification.

Heterochrony (evolutionary modifications in developmental timing and/or rates) is widely recognized as an important agent of morphological change. The adaptive significance of heterochronic changes might lie either in the advantages of the derived morphologies (organ size and shape) or the derived growth parameters themselves (rate and duration of growth). We have tested these hypotheses by comparing the growth rate, the duration of growth and the relative length of the adult tibia in Primates in a phylogenetic context. We report an evolutionary decrease in growth rates (paedochronocline) and an increase in the duration of growth (perachronocline), lying in the cline from the last common ancestor of Primates, passing through the last common ancestor of Haplorhini, that of Catarrhini, to the last common ancestor of the Hominidae. However, the variation in the relative length of the adult tibia does not show any phylogenetic pattern. The derived growth parameters in themselves (slower rate, longer duration) would be of adaptive significance and they would have been selected because a prolonged learning period prior to maturity conferred advantage. The proximate (developmental) causation of differences in bone growth rate were also investigated and it was found that cell production rate in the growth plates rather than the chondrocyte size, underlies the variation in bone growth rate.

Bone typology and growth rate: testing and quantifying ‘Amprino’s rule’ in the mallard ( Anas platyrhynchos)

Periosteal bone histology expresses its rate of deposition. This fundamental relationship between bone structure and growth dynamics, first assumed by Amprino many decades ago, was quantified in preliminary studies, but never statistically tested. Moreover, the precise typological characters of bone tissue linked to growth rate remained poorly known. Here, we present the first statistical analysis of ‘Amprino’s rule’, measured on comprehensive growth series of the mallard, Anas platyrhynchos. Growth rates were assessed by fluorescent labelling. Bone typology was described according to Ricqlès’ typological classification. Results show that the presence and proportion of primary osteons, two consequences of bone initial porosity at the time of its deposit, are strongly related to bone growth rate. However, no significant relationship between primary osteons orientation and bone growth rate could be detected, at least for osteonal orientations (longitudinal, laminar and reticular) and growth rates values observed in mallard long bones. These results suggest that Amprino’s rule holds for some major typological characters of primary compact bone tissues (i.e. primary osteons presence and proportion). However, it is irrelevant to some other characters (i.e. osteonal orientation), the meaning of which remains to be discovered.

Growth, bone mineralization, and heat and low oxygen tolerance in European whitefish ( Coregonus lavaretus L.) fed with graded levels of phosphorus

Trials were conducted to determine the dietary phosphorus (P) requirement of European whitefish, and to assess the effects of sub-optimal P feeding on growth, bone mineralization, lipid accumulation in the body and on heat and low-oxygen tolerance. Four replicate groups of whitefish fingerlings were fed in excess with one of five semipurified diets containing 4.4 to 14.9 g P kg −1. The P requirement was estimated by nonlinear curve fitting to bone mineralization and growth rate data. Dietary P and energy availabilities were measured at the determined requirement level. Fish fed no P supplement showed typical hypophosphatemia in poorly mineralized bones, a low whole-body P content and a low plasma phosphate concentration. Hypophosphatemic fish grew slower and had elevated whole body lipid concentrations. To obtain 95% of the maximum vertebra ash concentration and maximum growth, respectively, 6.5- and 6.2-g available P kg −1 diet was required. Fish fed low dietary P contents had higher whole body lipid levels than fish fed P at or above the determined requirement level. Hypophosphatemic fish had slightly, although statistically significant, lower upper lethal temperature than fish fed with adequate P contents (28.8 vs. 29.4 °C). Tolerance of low dissolved oxygen did not differ between fish fed low or high P contents (1.47 vs. 1.45 mg l −1).

Skeletal effects of developmental lead exposure in rats.

To identify possible direct and indirect mechanisms underlying the effects of lead on skeletal growth, 3 studies were conducted. In the first study, 1 male and 1 female pup/litter (n = 5 litters), were exposed ad libitum to 0, 825, or 2475 ppm lead acetate in the drinking water from gestational day 4 to euthanasia on day 55. Tibial strength was tested by 3-point bending and plasma levels of vitamin D metabolites were measured. A dose-dependent decrease of the load to failure was demonstrated but only in male pups. No differences in plasma levels of vitamin D metabolites were observed. In the second study, conducted to test if hormone treatment would attenuate the lead deficits, male and female pups were exposed to 0 or 2475 ppm lead acetate and then, from 30-60 days of age, received either saline vehicle, L-dopa, testosterone (males only), dihydrotestosterone (DHT, males only), or estradiol (females only). Lead exposure significantly reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period. Sex steroid replacement did not restore skeletal parameters in lead-exposed rats. L-Dopa increased plasma insulin-like growth factor 1 (IGF(1)) concentrations, rates of bone growth, and bone strength measures in controls while having no effect in lead-exposed pups. The third study was conducted at 100 days of age, when endocrine parameters have been shown to be normalized, to test for effects of lead exposure on bone formation during tibial limb lengthening (distraction osteogenesis, DO). Both DO gap x-ray density and proximal new endosteal bone formation were decreased in the distraction gaps of the lead-treated animals (p < 0.01). In conclusion, lead exposure reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period, and these effects could not be reversed by a growth hormone (GH) axis stimulator or by sex-appropriate hormones. Finally, lead exposure appears to specifically inhibit osteoblastogenesis in vivo in adult animals.

Collagen metabolism is markedly altered in the hypertrophic cartilage of growth plates from rats with growth impairment secondary to chronic renal failure.

Skeletal growth depends on growth plate cartilage activity, in which matrix synthesis by chondrocytes is one of the major processes contributing to the final length of a bone. On this basis, the present work was undertaken to ascertain if growth impairment secondary to chronic renal insufficiency is associated with disturbances of the extracellular matrix (ECM) of the growth plate. By combining stereological and in situ hybridization techniques, we examined the expression patterns of types II and X collagens and collagenase-3 in tibial growth plates of rats made uremic by subtotal nephrectomy (NX) in comparison with those of sham-operated rats fed ad libitum (SAL) and sham-operated rats pair-fed with NX (SPF). NX rats were severely uremic, as shown by markedly elevated serum concentrations of urea nitrogen, and growth retarded, as shown by significantly decreased longitudinal bone growth rates. NX rats showed disturbances in the normal pattern of chondrocyte differentiation and in the rates and degree of substitution of hypertrophic cartilage with bone, which resulted in accumulation of cartilage at the hypertrophic zone. These changes were associated with an overall decrease in the expression of types II and X collagens, which was especially marked in the abnormally extended zone of the hypertrophic cartilage. Unlike collagen, the expression of collagenase-3 was not disturbed severely. Electron microscopic analysis proved that changes in gene expression were coupled to alterations in the mineralization as well as in the collagen fibril architecture at the hypertrophic cartilage. Because the composition and structure of the ECM have a critical role in regulating the behavior of the growth plate chondrocytes, results obtained are consistent with the hypothesis that alteration of collagen metabolism in these cells could be a key process underlying growth retardation in uremia.

Regulation of growth plate chondrogenesis by bone morphogenetic protein-2.

Bone morphogenetic proteins (BMPs) regulate embryonic skeletal development. We hypothesized that BMP-2, which is expressed in the growth plate, also regulates growth plate chondrogenesis and longitudinal bone growth. To test this hypothesis, fetal rat metatarsal bones were cultured for 3 days in the presence of recombinant human BMP-2. The addition of BMP-2 caused a concentration-dependent acceleration of metatarsal longitudinal growth. As the rate of longitudinal bone growth depends primarily on the rate of growth plate chondrogenesis, we studied each of its three major components. BMP-2 stimulated chondrocyte proliferation in the epiphyseal zone of the growth plate, as assessed by [(3)H]thymidine incorporation. BMP-2 also caused an increase in chondrocyte hypertrophy, as assessed by quantitative histology and enzyme histochemistry. A stimulatory effect on cartilage matrix synthesis, assessed by (35)SO(4) incorporation into glycosaminoglycans, was produced only by the highest concentration of BMP-2. These BMP-2-mediated stimulatory effects were reversed by recombinant human Noggin, a glycoprotein that blocks BMP-2 action. In the absence of exogenous BMP-2, Noggin inhibited metatarsal longitudinal growth, chondrocyte proliferation, and chondrocyte hypertrophy, which suggests that endogenous BMPs stimulate longitudinal bone growth and chondrogenesis. We conclude that BMP-2 accelerates longitudinal bone growth by stimulating growth plate chondrocyte proliferation and chondrocyte hypertrophy.

Radiographic analysis of the growth rate of long bones in bustards

A serial radiographic study was conducted on seven houbara bustard (Chlamydotis undulata macqueenii), 10 rufous-crested bustard (Eupodotis ruficrista), four white-bellied bustard (Eupodotis senegalensis) and eight kori bustard (Ardeotis kori) chicks to determine the growth rate of long bones and to establish radiographic standards for assessing skeletal maturity. The growth rates of the tarsometatarsus and tibiotarsus in the bustard species investigated were similar to those in domestic fowl (Gallus domesticus) and some long-legged avian species. Maturation of long bones occurred earlier in houbara bustards compared with rufous-crested, white-bellied and kori bustards.

Bones, Muscles and Visceral Organs of Protein-Malnourished Rats (Rattus norvegicus) Grow More Slowly but for Longer Durations to Reach Normal Final Size

Starting at weaning (22 d), Sprague-Dawley rats were fed either a control diet high in protein (CT, 24% protein) or an isocaloric low protein diet (LPT, 4% protein) to determine how protein malnutrition alters the rate and timing of limb bone growth. Length and width measurements were taken from longitudinal radiographs to provide complete growth trajectories of both treatments. Data collection continued until rats reached adult size, which varied among diet-sex groups. The rats were then killed and five muscles and eight organs were weighed. A nonlinear Gompertz model was then fit to each trajectory for 13 skeletal measurements, producing parameters that described the rate and timing of growth for each rat, the unit of analysis. Parameter differences due to diet, sex and litter were tested by using a mixed-model, three-way ANOVA. For most measurements, the LPT rats were not significantly smaller than the CT rats, for the model's prediction of final size. Bone length was significantly less affected than width. The instantaneous initial growth rate, maximum rate of growth and rate of growth decay were significantly higher in the control rats for all measurements. The rats fed the low protein diet grew for significantly longer periods of time. For all muscles and most organs relative to body size, there was no difference between rats fed the two diets. The exceptions, eyes and brains, were proportionally larger in the LPT rats, suggesting that these organs receive nutritional priority during growth. For the systems in this study, structures that grow or have the potential for extended growth are less affected by the nutritional insult.

Process Heterochronies in Endochondral Ossification

Heterochrony, evolutionary changes in developmental rates and timing, is a key concept in the construction of a synthesis of development and evolution. Heterochronic changes in vertebrate evolution have traditionally been identified through plesiomorphic–apomorphic comparisons of bone growth. This methodological framework assumes that observed heterochronies are the outcome of dissociations of developmental processes in time. Recent findings of non-heterochronic developmental changes underlying morphological heterochrony invalidate this assumption. In this paper, a function for bone growth (at the organ level) has been mathematically deduced from the underlying developmental mechanisms. The temporal domain of the model spans from the time at maximum growth rate, after the formation of growth plates, to the time at atrophy of the proliferating stratum of cells. Three organizational levels were considered: (a) cell kinetics of endochondral ossification, (b) variation of bone growth rates and (c) variation of accumulated bone growth with increasing age. This quantitative model provides an excellent tool to deal with the problem of the developmental basis of morphological change. I have modelled potential evolutionary changes on the system at different levels of biological organization. This new framework involves an epistemological shift in heterochronic analysis from a pattern-oriented inductive way to a process-oriented deductive way. The analysis of the relationships between the evolutionary alterations of endochondral ossification and the morphological expression of these changes reveals that observed pattern heterochronies can be the outcome of different process heterochronies. Moreover, I discuss at length the heteroposic hypothesis, that evolutionary changes in the tight regulation of the amount of protein synthesized by a cell population during development would underlie acceleration or deceleration in cases of evolutionary changes in the initial number of proliferating cells at growth plates. Future research on the genetic basis of process heterochronies and heteroposies will complete our understanding of these evolutionary phenomena.

Periosteal bone growth rates in extant ratites (ostriche and emu). Implications for assessing growth in dinosaurs

The first quantitative experimental data on growth dynamics of the primary cortical bone of young ratites demonstrate the following. 1) From hatching to 2 months of age, cortical thickness remains constant, thereby expressing equilibrium between periosteal bone deposition and an endosteal bone resorption. 2) Radial growth rates of the diaphyseal bone cortex are high (10–40 μm·day –1 on average – maximum 80 μm·day –1 ) in the hindlimb (femur, tibiotarsus and tarsometatarsus). Wing bones are smaller and later developed. They have lower rates of radial osteogenesis (2–14 μm·day –1). 3) High growth rates are linked to densely vascularized primary bone belonging to the reticular or laminar tissue types. Growth rates fall when bone vascular density decreases. These results emphasize the importance of examining a large number of skeletal elements in order to build a precise knowledge of the general relationship between bone growth rate and bone tissue type. They also stress the potential of bone growth rate quantification among extinct tetrapods, including non-avian dinosaurs.

2-Methoxyestradiol Inhibits Longitudinal Bone Growth in Normal Female Rats

2-Methoxyestradiol (2-MeO-E(2)), a major metabolite of 17beta-estradiol, may function as a physiological tumor suppressor and is being investigated for clinical applications. It has been reported to target rapidly dividing cells. We investigated the effects of 2-MeO-E(2) on the growth plate of young rats because normal longitudinal bone growth requires rapid proliferation of cartilage and endothelial cells. Sexually mature (3-month-old) normal female rats were treated with 2-MeO-E(2) (100 mg/kg/day) for 13 days and it was found to have no effect on uterine weight but reduced serum cholesterol. The estrogen metabolite had no effect on either cortical or cancellous bone. In contrast, 2-MeO-E(2) dramatically reduced longitudinal bone growth rate at the proximal tibia from 55 +/- 2 to 20 +/- 2 microm/day (P < 0.001) and growth plate thickness from 153 +/- 14 to 70 +/- 6 microm (P < 0.001). The latter decrease was due to significant reductions in the height of both the proliferative (P < 0.001) and the hypertrophic (P < 0.001) zones. These results in normal female rats demonstrate that 2-MeO-E(2) inhibited longitudinal bone growth but had no effect on either radial bone growth or cancellous bone turnover. 2-MeO-E(2) was shown by these studies to have the ability to discriminate between bone and cartilage, as well as between reproductive and nonreproductive estrogen-target tissues. Thus, 2-MeO-E(2) is a naturally produced estrogen metabolite that demonstrates unique tissue selectivity.

Lactam formation increases receptor binding, adenylyl cyclase stimulation and bone growth stimulation by human parathyroid hormone (hPTH)(1-28)NH2.

Human parathyroid hormone (1-28)NH2 [hPTH(1-28)NH2] is the smallest of the PTH fragments that can fully stimulate adenylyl cyclase in ROS 17/2 rat osteoblast-like osteosarcoma cells. This fragment has an IC50 of 110 nM for displacing 125I-[Nle8,18,Tyr34]bovine PTH(1-34)NH2 from HKRK B7 porcine kidney cells, which stably express 950,000 human type 1 PTH/PTH-related protein (PTHrP) receptors (PTH1Rs) per cell. It also has an EC50 of 23.9 nM for stimulating adenylyl cyclase in ROS 17/2 cells. Increasing the amphiphilicity of the alpha-helix in the residue 17-28 region by replacing Lys27 with Leu and stabilizing the helix by forming a lactam between Glu22 and Lys26 to produce the [Leu27]cyclo(Glu22-Lys26)hPTH(1-28)NH2 analog dramatically reduced the IC50 for displacing 125I-[Nle8,18,Tyr34]bPTH(1-34)NH2 from hPTH1Rs from 110 to 6 nM and dropped the EC50 for adenylyl cyclase stimulation in ROS 17/2 cells from 23.9 to 9.6 nM. These modifications also increased the osteogenic potency of hPTH(1-28)NH2. Thus, hPTH(1-28)NH2 did not significantly stimulate either femoral or vertebral trabecular bone growth in rats when injected daily at a dose of 5 nmol/100 g body weight for 6 weeks, beginning 2 weeks after ovariectomy (OVX), but it strongly stimulated the growth of trabeculae in the cancellous bone of the distal femurs and L5 vertebrae when injected at 25 nmol/100 g body weight. By contrast [Leu27]cyclo(Glu22-Lys26)hPTH(1-28)NH2 significantly stimulated trabecular bone growth when injected at 5 nmol/100 g of body weight. Thus, these modifications have brought the bone anabolic potency of hPTH(1-28)NH2 considerably closer to the potencies of the larger PTH peptides and analogs.

Long bone histology of the hadrosaurid dinosaur Maiasaura peeblesorum: growth dynamics and physiology based on an ontogenetic series of skeletal elements

ABSTRACT Ontogenetic changes in the bone histology of Maiasaura peeblesorum are revealed by six relatively distinct but gradational growth stages: early and late nestling, early and late juvenile, sub-adult, and adult. These stages are distinguished not only by relative size but by changes in the histological patterns of bones at each stage. In general, the earliest stages are marked by spongy bone matrix with large vascular canals. Through growth, the cortical bone differentiates into fibro-lamellar tissue that tends to become more regularly layered in the outer cortex. By the sub-adult stage, lines of arrested growth (LAGs) begin to appear regularly. Resorption lines and substantial Haversian substitution in many long bones also begin to appear at this stage, and the external cortex has a lamellar-zonal structure in some bones that indicates imminent cessation of growth. Judging by the rates of apposition of similar bone tissues in living amniotes, and by the number and placement of LAGs, these patterns suggest that young Maiasaura nestlings grew at very high rates, and at high and moderately high rates during later nestling, juvenile, and sub-adult stages, slowing to low and very low growth rates in adults (7–9 m total length). The nesting period would have lasted one to two months, late juvenile size (3.5 meters) would have been reached in one or two years, and adult size in six to eight years, depending on the basis for extrapolating bone growth rates. The histological tissues, patterns, and inferred growth rates of the bones of Maiasaura are completely different from those of living non-avian reptiles, generally similar to those of most other dinosaurs and pterosaurs for which data are available, and much like those of extant birds and mammals. No living reptiles (except birds) grow to adult size at these rates, nor do they show these histological patterns. We conclude that Maiasaura did not grow at all like living non-avian reptiles, which cannot be considered informative models for most aspects of dinosaurian growth (or physiology, to the extent that growth rates reflect metabolism). The use of lines of arrested growth (LAGs) to infer dinosaurian physiology has never been tested and is not supported by independent lines of evidence; their use in calculating age is also more complex than previously suggested and should not be based on single bones.

Nonheterochronic developmental changes underlie morphological heterochrony in the evolution of the Ardeidae

Abstract Evolutionary changes in developmental timing and rates (heterochrony) are a source of morphological variation. Here we explore a central issue in heterochronic analysis: are the alterations in developmental timing and rates the only factor underlying morphological heterochrony? Tarsometatarsal growth through endochondral ossification in Ardeidae evolution has been taken as a case study. Evolutionary changes in bone growth rate (morphological heterochrony) might be either (a) the result of alterations in the mitotic frequency of epiphyseal chondrocytes (process-heterochrony hypothesis), or (b) the outcome of alterations in the number of proliferating cells or in the size of hypertrophic chondrocytes (structural hypothesis). No correlation was found between tarsometatarsal growth rates and the frequency of cell division. However, bone growth rates were significantly correlated with the number of proliferating cells. These results support the structural hypothesis: morphological acceleration and deceleration are the outcome of evolutionary changes in one structural variable, the number of proliferating cells.

Different bone growth rates are associated with changes in the expression pattern of types II and X collagens and collagenase 3 in proximal growth plates of the rat tibia.

Skeletal growth depends on endochondral ossification in growth plate cartilage, where proliferation of chondrocytes, matrix synthesis, and increases in chondrocyte size all contribute to the final length of a bone. To learn more about the potential role of matrix synthesis/degradation dynamics in the determination of bone growth rate, we investigated the expression of matrix collagens and collagenase 3 in tibial growth plates in three age groups of rats (21, 35, and 80 days after birth), each characterized by specific growth rates. By combining stereological and in situ hybridization techniques, it was found that the expression of matrix collagens and collagenase 3 was specifically turned on or off at specific stages of the chondrocyte-differentiation cycle, and these changes occurred as a temporal sequence that varied depending of animal growth rate. Furthermore, the expression of these matrix proteins by a growth plate chondrocyte was found to be sped up or slowed down depending of the growth rate. In addition to expression of types II and X collagen, collagenase-3 expression was found to constitute a constant event in the series of changes in gene expression that takes place during the chondrocyte-differentiation process. Collagenase-3 expression was found to show a biphasic pattern: it was intermittently expressed at the proliferative phase and uniformly expressed at the hypertrophic stage. An intimate relationship between morphological and kinetic changes associated with chondrocyte hypertrophy and changes in the expression pattern of matrix collagens and collagenase 3 was observed. Present data prove that the matrix synthesis/degradation dynamics of the growth plate cartilage varied depending on growth rate; these results support the hypothesis that changes in matrix degradation and synthesis are a critical link in the sequence of tightly regulated events that lead to chondrocytic differentiation.

Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy.

Longitudinal bone growth, and hence stature, are functions of growth plate chondrocyte proliferation and hypertrophy. Insulin-like growth factor 1 (Igf1) is reputed to augment longitudinal bone growth by stimulating growth plate chondrocyte proliferation. In this study, however, we demonstrate that chondrocyte numbers and proliferation are normal in Igf1 null mice despite a 35% reduction in the rate of long bone growth. Igf1 null hypertrophic chondrocytes differentiate normally in terms of expressing specialized proteins such as collagen X and alkaline phosphatase, but are smaller than wild-type at all levels of the hypertrophic zone. The terminal hypertrophic chondrocytes, which form the scaffold on which long bone growth extends, are reduced in linear dimension by 30% in Igf1 null mice, accounting for most of their decreased longitudinal growth. The expression of the insulin-sensitive glucose transporter, GLUT4, is significantly decreased and the insulin-regulated enzyme glycogen synthase kinase 3beta (GSK3) is hypo-phosphorylated in Igf1 null chondrocytes. Glycogen levels were significantly decreased and ribosomal RNA levels were reduced by almost 75% in Igf1 null chondrocytes. These data suggest that Igf1 promotes longitudinal bone growth by 'insulin-like' anabolic actions which augment chondrocyte hypertrophy.

Skeletal mass, chemistry, and growth during and after multiple reproductive cycles in the rat

There are dramatic changes in skeletal physiology and metabolism to accommodate the mineral requirements of the developing fetus during pregnancy and milk production during lactation. The purpose of this study was to document changes in skeletal growth, chemistry, and mass during and after multiple reproductive cycles in the rat, with emphasis on the putative reconstitution of the skeleton after lactation. To determine skeletal changes, experimental groups included rats at the end of the first and second lactation, at the end of the second pregnancy, and at various times after the first and second lactation. These groups were also compared with aged-matched, nulliparous animals. There were decreases in femoral ash weights and bone mineral densities (BMDs) during the first and second lactations, but accelerated rates of gain after lactation, compared with the nulliparous controls. The changes in bone ash were even more pronounced when normalized to the maternal body weight changes during and after the reproductive cycles. The rates and amount of bone mineral (ash) gain after the first and second reproductive cycles were similar; however, neither bone mineral nor BMD returned to levels found in nulliparous animals after the first and subsequent reproductive cycle. There was also a decrease in ash/dry weight ratio of the femur during the second lactation, suggesting a preferential loss of more mineralized bone. This decrease in ash/dry weight ratio reversed after lactation, indicating a relative accumulation of bone mineral during the postlactational period. As expected, endochondral growth was substantially suppressed during lactation, but rebounded during the postlactational period. These data collectively support the notion that the female rat has excess skeletal mass to accommodate losses associated with the first reproductive cycle. After the first reproductive cycle, a new optimal skeletal mass is achieved. These data also demonstrate that the postlactational period is “anabolic” with accelerated rates of bone growth and accumulation of bone mineral and bone mineral density with increases in the ratios of the inorganic to organic composition of the bone. This postlactational recovery phase may serve to at least partially reconstitute skeletal mineral depleted during lactation and perhaps to prepare the skeleton for the next reproductive cycle.

Lack of Effect of GnRH Agonists on Final Height in Girls with Advanced Puberty: A Randomized Long-Term Pilot Study

GnRH agonists improve final height in girls with “true” precocious puberty. To test if a comparable effect can be obtained in older girls, we performed a long-term controlled study in 30 caucasian girls whose puberty started between 8.4 and 10 yr (9.4 ± 0.1 yr), a variant of normal called “advanced” puberty. At entry into trial, these girls had clinical, biological, and sonographic manifestations of puberty and a bone age greater than 10.9 yr. They were randomized 2:1 to receive 3.75 mg triptorelin im every 4 weeks for 2 yr (n = 20, group I) or no treatment (n = 10, group II). Mean height at inclusion was 135.2 ± 4.3 cm (+0.6 sds) in group I, 136.1 ± 4.2 cm (+0.8 sds ) in group II, with target height 157.6 ± 4.3 cm (group I) and 157.8 ± 4.7 cm (group II), and predicted height (Bayley-Pinneau) 154.1 ± 3.9 cm and 155.2 ± 3.7 cm. Although GnRH agonists transiently delayed sexual maturation as well as bone age and growth rate, they had no clear-cut long-standing effect, and final height was comparable in treated (157.6 ± 4.0 cm) and untreated girls (156.1 ± 5.3 cm) (NS).

Hypertrophy of growth plate chondrocytes in vivo is accompanied by modulations in the activity state and surface area of their cytoplasmic organelles.

The rate of longitudinal bone growth is regulated primarily by modulations in the activity of epiphyseal plate hypertrophic chondrocytes, these being manifested as changes in cell and matrix volume. It was the purpose of this study to ascertain whether the cytoplasmic organelles representing the cellular production apparatus, i.e. rough endoplasmic reticulum, Golgi apparatus and mitochondria, contribute to these changes by modulating their rate of activity or by increasing/decreasing the surface area and/or volume of their membranes. Using rats at different stages of growth, the surface areas and volumes of the three organellar systems were quantified in epiphyseal plate chondrocytes at the onset and termination of hypertrophy by ultrastructural stereology. Matrix synthesis during the same span was assessed by monitoring the production of its principal components, namely, fibrillar collagen (ultrastructural morphometry) and glycosaminoglycans (quantitative (35)S-autoradiography). Each organelle adapts to increases (21- to 35-day-old rats) and decreases (35- to 80-day-old rats) in growth rate by its own individual combination of the two alternative mechanisms, but modulations in the level of activity predominate over alterations in the surface area or volume of their membranes. These findings point to the danger of relying solely on data gleaned from a quantitative ultrastructural analysis of organellar parameters and emphasise the necessity of conducting functional assays in parallel, as performed here.

Postnatal growth of broilers in response to in ovo administration of chicken growth hormone

The effect of in ovo administration of chicken growth hormone (cGH) on growth rate and efficiency of gain, organ, and long bone growth of 42-d-old broiler chickens was investigated. Eggs were injected once with 100 microL vehicle (0.03 M NaHCO3, 0.15 M NaCl, pH 8.3) per embryo or vehicle containing 100 ng cGH/100 microL per embryo (n = 630 eggs total) on one of the following Days: 1, 4, or 7 through 18 of embryogenesis. There was no significant difference in hatchability between control and cGH treatment groups on any given injection day. Cumulative feed conversion of all treatment groups was improved relative to their respective control groups (P < 0.05). In ovo administration of cGH on Day 15 or 16 of incubation increased body weights (P < 0.01) of female broilers. On the other hand, body weights of male broilers were significantly increased by treatment on Day 1 (P < 0.04). Breast weights of female broilers from treatment groups Day 15 or 16 were increased (P < 0.01, P < 0.05, respectively). Liver weights of female broilers from treatment groups Day 1 and 15 were increased (P < 0.05, P < 0.01, respectively). In contrast, in ovo administration of cGH on Day 11 of incubation increased liver weights of male broilers (P < 0.03). There was no significant difference between control and treatment groups, in terms of heart or leg weights, or in Warner-Bratzler shear force of Pectoralis profundus muscle. Hydroxyproline concentration and cross-sectional area of female broiler tibias from treatment groups Day 11 or Day 16 were increased (P < 0.05), and ultimate breaking strength (stress) of tibias from the same groups was reduced (P < 0.05). In ovo administration of cGH altered growth and tissue development of broiler chickens in a time by sex dependent fashion.