Lactoferrin expression and secretion in the stallion epididymis

Lactoferrin is one of the most abundant proteins secreted by the stallion epididymis, but its cellular localization and regulation remain unknown. This study was designed to address the following objectives: (1) identify the epididymal cell types producing lactoferrin in pre-pubertal, peri-pubertal and post-pubertal animals; (2) demonstrate that lactoferrin binds to stallion sperm; and (3) determine if testosterone and estradiol regulate lactoferrin secretion in vitro. Using an immunohistochemical method, lactoferrin was localized in the cytoplasm of principal cells in the corpus and cauda of peri- and post-pubertal animals. The epididymis of pre-pubertal animals did not express lactoferrin. Immunolabeling of lactoferrin was also observed on the mid-piece and tail of the sperm. The role of estradiol and testosterone in regulating secretion of lactoferrin in the post-pubertal epididymis was investigated using tissue culture methods. Lactoferrin concentration in the culture media was determined by validated enzyme-linked immunosorbent assays (ELISA). Testosterone did not increase the concentration of lactoferrin in the media in any epididymal region. In contrast, estradiol-17β significantly increased the concentration of lactoferrin in the media containing tissue from the cauda. In conclusion, the expression of lactoferrin was found in the cytoplasm of principal cells in the corpus and cauda of the epididymis in peri- and post-pubertal stallions but not pre-pubertal stallions. Furthermore, lactoferrin binds to sperm, suggesting a biological role for protection or regulation of sperm in the corpus and cauda. In addition, estrogen appears to regulate lactoferrin secretion in the cauda of the epididymis in post-pubertal stallions.     

Developmental competence and mRNA expression of preimplantation in vitro-produced embryos from prepubertal and postpubertal cattle and their relationship with apoptosis after intraovarian administration of IGF-1

Recombinant human Insulin-like growth factor-I (hIGF-1) was administered to one ovary of prepubertal and postpubertal cattle to determine its effects on (1) oocyte developmental competence, (2) the expression pattern of six developmentally important genes (GLUT3, GLUT8, AKT1, BCL-XL, BAD, and BAX), and (3) its relationship with apoptosis (female Holstein-Friesian). Oocytes were retrieved from 7- to 10-mo-old prepubertal dairy calves (preP), 11- to 18-mo-old postpubertal heifers (postP), and cows via ultrasound-guided follicular aspiration. Immature oocytes were matured in vitro then fertilized and cultured up to the blastocyst stage. Apoptosis was determined by terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) in 8-d blastocysts. Similar low blastocyst yields were observed in the IGF-1-treated preP group (11.2 ± 2.4%), the control preP group (10.4 ± 3.0%), and in the IGF-1 postP group (10.9 ± 2.3%). These were lower (P ≤ 0.01) compared with the control postP group (21.2 ± 3.8%) and with cows (23 ± 3.7%). The expression profile of the six genes was partly affected by age and IGF-1 treatment. Apoptosis was correlated with the age of the oocyte donors and was increased in blastocysts derived from prepubertal heifers. Results show that apoptosis is a critical feature of the acquisition of developmental competence of oocytes from prepubertal cattle and that IGF-1 did not beneficially affect oocyte developmental competence.     

Exposure of pregnant dairy heifer to magnetic fields at 60 Hz and 30 microT

Thirty-two pregnant Holstein heifers weighing 499 +/- 45 kg, at 3.1 +/- .7 months of gestation and 21 +/- 2.0 months of age were confined and exposed to 30 microT magnetic fields (MFs) and a 12 h light/12 h dark light cycle. The heifers were divided into two replicates of 16 animals. Each replicate was divided into two groups of eight animals each, one group the non-exposed and the second, the exposed group. The animals were subjected to the different treatments for 4 weeks. After 4 weeks, the animals switched treatment, the exposed group becoming the non-exposed group and vice versa. Then the treatment continued for 4 more weeks. Catheters were inserted into the jugular vein, and blood samples were collected twice a week to estimate the concentration of progesterone (P4), melatonin (MLT), prolactin (PRL), and insulin-like growth factor 1 (IGF-1). Feed consumption was measured daily. The results indicated that exposure of pregnant heifers to MF similar to those encountered underneath a 735 kV high tension electrical power line for 20 h/day during a period of 4 weeks produces slight effects. This is evidenced by statistically significant higher body weight (1.2%), higher weekly body weight gain (30%), and decreases in the concentration of PRL (15%) and IGF-1 (4%) in blood serum. The absence of abnormal clinical signs and the absolute magnitude of the significant changes detected during MF exposure, make it plausible to preclude any major animal health hazard.     

Relationship of liver and skeletal muscle IGF-1 mRNA to plasma GH profile, production of IGF-1 by liver, plasma IGF-1 concentrations, and growth rates of cattle

Growth hormone (GH), insulin-like growth factor-1 (IGF-1), and thyroid hormone (T3 and T4) concentrations in blood plasma of 18 crossbred cattle (six bulls, six steers, and six heifers) were measured over an 8-hr period. One week later at slaughter, IGF-1 production by liver slices and IGF-1 mRNA concentrations in skeletal muscle and liver were measured. Bulls had higher (P less than 0.05) mean plasma GH and GH peak amplitudes (P less than 0.01) than heifers, and values for steers were intermediate between bulls and heifers. Baseline GH concentrations and number of GH peaks were not significantly different for the three groups. Bulls had 1.6-fold (P less than 0.01) and 3.0-fold (P less than 0.01) greater liver IGF-1 mRNA concentrations than steers or heifers, respectively, whereas the steers had 1.8-fold (P less than 0.05) greater IGF-1 mRNA in liver than heifers. Production of IGF-1 by liver slices was greater (P less than 0.05) in bulls than steers or heifers. Bulls had 1.3-fold greater plasma IGF-1 than steers (P less than 0.01), whereas steers had 1.8-fold greater plasma IGF-1 than heifers (P less than 0.01). There were no significant differences in concentrations of skeletal muscle IGF-1 mRNA between the three groups of animals. Liver IGF-1 mRNA, liver IGF-1 production, and plasma IGF-1 were all significantly correlated with gain and mean GH peak amplitude, but not with GH baseline, GH peak frequency, or concentrations of T3 and T4. Concentrations if IGF-1 mRNA in skeletal muscle were not correlated to gain or any parameter of the GH profile. Plasma concentrations of T3 were significantly (P less than 0.05) negatively correlated to plasma GH baseline concentrations. Muscle IGF-1 mRNA concentration was negatively related to plasma T4 and T3. The results of this study suggest that the cascade of events starting with secretion of GH from the pituitary, expression of liver IGF-1 mRNA, and secretion of IGF-1 by the liver are important phenomena for growth of cattle.     

A novel role for IGF-1R in p53-mediated apoptosis through translational modulation of the p53-Mdm2 feedback loop

Insulin-like growth factor 1 receptor (IGF-1R) is important in cancer cell growth and survival and has been implicated in cancer pathophysiology and treatment. Here we report a novel function for IGF-1R in p53-dependent apoptotic response. We show that inhibition or loss of IGF-1R activity reduces translational synthesis of p53 and Mdm2 protein. Notably, IGF-1R inhibition increases p53 protein stability by reducing p53 ubiquitination and maintains p53 at low levels by decreasing p53 synthesis, thus rendering p53 insensitive to stabilization after DNA damage. The accumulation and apoptosis of DNA-damage-induced p53 is therefore reduced in Igf-1r(-/-) mouse embryonic fibroblasts or tumor cells treated with the IGF-1R inhibitor. Furthermore, we find that inhibition of IGF-1R reduces p53 and Mdm2 translation through a gene-specific mechanism mediated by the respective 5' untranslated region of p53 and mdm2 messenger RNA. The eukaryotic translation initiation factor 4F complex is also involved in this translational inhibition. These results demonstrate an unexpected role for translational control by IGF-1R in p53-mediated apoptosis.     

Insulin like growth factor 1 and regulation of ovarian function in mammals

Various growth factors have been proposed to play endocrine and/or paracrine role in mammalian ovarian follicular development. The insulin like growth factor 1 (IGF-1) is one such factor. More and more reports now support the existence of an intra-ovarian IGF system including receptors and binding proteins. The role of IGF-1 in ovary is to amplify gonadotropin hormone action in terms of increased steroidogenesis by ovarian granulosa cell and granulosa cell proliferation. The synthesis and proteolysis of insulin like growth factor binding proteins, under the control of follicle stimulating hormone, regulate the intra-follicular availability of IGF-1, which further determines the sensitivity of granulosa cells to gonadotropins. Besides gonadotropins, IGF-1 has been implicated in somatotropin hormone action in the ovarian function. Exact mechanism of IGF-1 action in the ovarian follicles needs to be worked out to elucidate whether or not IGF-1 is indispensable in addition to know endocrine factors like gonadotropic and ovarian steroid hormones. This will pave the way for better understanding of control(s) which ensure final development of dominant follicle(s) and atresia of other follicles of the cohort.     

Organisation of collagen fibrils in tendon: changes induced by an anabolic steroid

The organisation of tendon collagen fibrils has been studied by electron microscopy after treatment with an anabolic steroid hormone in a short-term and a long-term study. The effect of anabolic steroids is of interest because of their use in competitive sports and in clinical therapy. In a functional experimental model the unexpected occurrence of dysplastic as well as ruptured and dissociated collagen fibrils was revealed. The striking time-dependent collagen dysplasia and other pathological findings strongly suggest that in mice anabolic steroid treatment predisposes to tendon rupture especially when the animals are exercised. The possible underlying mode of action of anabolic steroid hormone on connective tissue is discussed.     

High levels of glucose induce apoptosis in cardiomyocyte via epigenetic regulation of the insulin-like growth factor receptor

Diabetic hyperglycemia result in cardiovascular complications, but the mechanisms by which high levels of glucose (HG) cause diabetic cardiomyopathy are not known. We investigate whether HG-induced repression of insulin-like growth factor 1 receptor (IGF-1R) mediated by epigenetic modifications is one potential mechanism. We found that HG resulted in decreased IGF-1 receptor (IGF-1R) mRNA levels, and IGF-1R protein when compared with H9C2 rat cardiomyocyte cells incubated in normal glucose. HG also induced apoptosis of H9C2 cells. The effects of HG on reduced expression of IGF-1R and increased apoptosis were blocked by silencing p53 with small interference RNA but not by non-targeting scrambled siRNA. Moreover, HG negatively regulated IGF-1R promoter activity as determined by ChIP analysis, which was dependent on p53 since siRNA-p53 attenuated the effects of HG on IGF-1R promoter activity. HG also increased the association of p53 with histone deacetylase 1 (HDAC1), and decreased the association of acetylated histone-4 with the IGF-1R promoter. Furthermore, HDAC inhibitor relieved the repression of IGF-1R following HG state. These results suggest that HG-induced repression of IGF-1R is mediated by the association of p53 with the IGF-1R promoter, and by the subsequent enhanced recruitment of chromatin-modifying proteins, such as HDAC1, to the IGF-1R promoter-p53 complex. In conclusion, our data demonstrate that HG decreases expression of IGF-1R and decreases the association of acetylated histone-4 with the IGF-1R promoter. These studies may help delineate the complex pathways regulating diabetic cardiomyopathy, and have implications for the development of novel therapeutic strategies to prevent diabetic cardiomyopathy by epigenetic regulation of IGF-1R.     

Two-spotted spider mite reared on resistant eggplant affects consumption rate and life table parameters of its predator,Typhlodromus bagdasarjani (Acari: Phytoseiidae)

The blue tick, Rhipicephalus microplus, threatens cattle production in most tropical and subtropical areas of the world. Delayed skin hypersensitivity reactions are thought to cause Nguni cattle to be more resistant to R. microplus than Bonsmara cattle yet the cellular mechanisms responsible for these differences have not been classified. Tick counts and inflammatory cell infiltrates in skin biopsies from feeding sites of adult R. microplus ticks were determined in 9-month-old Nguni and Bonsmara heifers to determine the cellular mechanisms responsible for tick immunity. Nguni heifers (1.7 ± 0.03) had lower (P < 0.05) tick counts than the Bonsmaras (2.0 ± 0.03). Parasitized sites in Nguni heifers had higher counts of basophils, mast and mononuclear cells than those in the Bonsmara heifers. Conversely, parasitized sites in Nguni heifers had lower neutrophil and eosinophil counts than those in the Bonsmara heifers. Tick count was negatively correlated with basophil and mast cell counts and positively correlated with eosinophil counts in both breeds. In the Bonsmara breed, tick count was positively correlated with mononuclear cell counts. Cellular responses to adult R. microplus infestations were different and correlated with differences in tick resistance in Nguni and Bonsmara cattle breeds. It is essential to further characterise the molecular composition of the inflammatory infiltrate elicited by adult R. microplus infestation to fully comprehend immunity to ticks in cattle.     

In vivo oocyte IGF-1 priming increases inner cell mass proliferation of in vitro-formed bovine blastocysts

Studies addressing the effects of supraphysiological levels of IGF-1 on oocyte developmental competence are relevant for unravelling conditions resulting in high bioavailability of IGF-1, such as the polycystic ovary syndrome (PCOS). This study investigated the effects of supraphysiological levels of IGF-1 during in vivo folliculogenesis on the morula-blastocyst transition in bovine embryos. Compacted morulae were non-surgically collected and frozen for subsequent mRNA expression analysis (IGF1R, IGBP3, TP53, AKT1, SLC2A1, SLC2A3, and SLC2A8), or underwent confocal microscopy analysis for protein localization (IGF1R and TP53), or were cultured in vitro for 24 h. In vitro-formed blastocysts were subjected to differential cell staining. The mRNA expression of SLC2A8 was higher in morulae collected from cows treated with IGF-1. Both IGF1R and TP53 protein were present in the plasma membrane and cytoplasm. IGF-1 treatment did not affect protein localization of both IGF1R and TP53. In vitro-formed blastocysts derived from morulae recovered from IGF-1-treated cows displayed a higher number of cells in the inner cell mass (ICM). Total cell number (TCN) of in vitro-formed blastocysts was not affected. A higher mean ICM/TCN proportion was observed in in vitro-formed blastocysts derived from morulae collected from cows treated with IGF-1. The percentage of in vitro-formed blastocysts displaying a low ICM/TCN proportion was decreased by IGF-1 treatment. In vitro-formed blastocysts with a high ICM/TCN proportion were only detected in IGF-1 treated cows. Results show that even a short in vivo exposure of oocytes to a supraphysiological IGF-1 microenvironment can increase ICM cell proliferation in vitro during the morula to blastocyst transition.     

Mechanism of delayed ovulation in a vespertilionid bat, scotophilus heathi: role of gonadotropin, insulin, and insulin-like growth factor-1

The aim of this study was to evaluate the effects of luteinizing hormone (LH), follicle-stimulating hormone (FSH), insulin, and insulin-like growth factor-1 (IGF-1) on ovarian androstenedione synthesis to understand the mechanism responsible for delayed ovulation in Scotophilus heathi. We found that LH stimulated a dose-dependent increase in androstenedione synthesis by the ovary in vitro. This study also showed a clear seasonal variation in the ability of the ovary to produce androstenedione in vitro in response to LH and FSH stimulation. In response to LH and FSH, maximum quantities of androstenedione were produced during recrudescence in November. The same doses of gonadotropins during the preovulatory period in February stimulated comparatively low androstenedione secretion by the ovary. On the basis of these data, we suggest that in S. heathi, ovarian responsiveness to LH and FSH peaks during recrudescence. This study also showed a seasonal variation in the effects of insulin and IGF-1 on ovarian androstenedione production in vitro. Peak ovarian responsiveness to insulin and IGF-1 was observed during quiescence in September. It is hypothesized that increased insulin/IGF-1 sensitivity during September may be responsible for increased responsiveness to LH. Increased LH release, if coincident with the period of enhanced ovarian responsiveness to LH, may result in the excessive androstenedione production responsible for delayed ovulation in S. heathi.     

Effects of acute unilateral ovariectomy to pre-pubertal rats on steroid hormones secretion and compensatory ovarian responses

In the present study we analyzed the existence of asymmetry in the secretion of steroid hormones in pre-pubertal female rats treated with unilateral ovariectomy (ULO) or unilateral perforation of the abdominal wall (sham-surgery). Treated rats were sacrificed at different times after surgery. Since sham-surgery had an apparent effect on the age of first vaginal estrous (FVE) and serum levels hormone, the results of the sham surgery groups were used to assess the effects of their respective surgery treatment groups. On the day of FVE, compensatory ovulation (CO) and compensatory ovarian hypertrophy (COH) were similar in animals with ULO, regardless of the ovary remaining in situ. In ULO treated animals, progesterone (P4) levels were higher than in animals with sham-surgery one hour after treatment but lower in rats sacrificed at FEV. Left-ULO resulted in lower testosterone (T) concentration 48 and 72 hours after surgery. In rats with Right-ULO lower T concentrations were observed in rats sacrificed one or 72 hours after surgery, and at FVE. ULO (left or right) resulted in lower estradiol (E2) concentrations one or 72 hours after treatment. In rats with Left-ULO, E2 levels were higher 48 hours after surgery and at FVE. Left-ULO resulted in higher levels of follicle stimulating hormone (FSH) five hours after surgery and at FVE. FSH levels were higher in rats with Right-ULO sacrificed on FVE. The present results suggest that in the pre-pubertal rat both ovaries have similar capacities to secrete P4, and that the right ovary has a higher capacity to secrete E2. Taken together, the present results support the idea that the effects of ULO result from the decrease in glandular tissue and changes in the neural information arising from the ovary.     

Doxorubicin Impairs the Insulin-Like Growth Factor-1 System and Causes Insulin-Like Growth Factor-1 Resistance in Cardiomyocytes

BackgroundInsulin-like growth factor-1 (IGF-1) promotes the survival of cardiomyocytes by activating type 1 IGF receptor (IGF-1R). Within the myocardium, IGF-1 action is modulated by IGF binding protein-3 (IGFBP-3), which sequesters IGF-1 away from IGF-1R. Since cardiomyocyte apoptosis is implicated in anthracycline cardiotoxicity, we investigated the effects of the anthracycline, doxorubicin, on the IGF-1 system in H9c2 cardiomyocytes.ConclusionsDoxorubicin down-regulates IGF-1R and up-regulates IGFBP-3 via p53 and oxidative stress in H9c2 cells. This leads to resistance to IGF-1 that may contribute to doxorubicin-initiated apoptosis. Further studies are needed to confirm these findings in human cardiomyocytes and explore the possibility of manipulating the IGF-1 axis to protect against anthracycline cardiotoxicity.     

Mode of growth hormone action in osteoblasts

Growth hormone (GH) affects bone size and mass in part through stimulating insulin-like growth factor type 1 (IGF-1) production in liver and bone. Whether GH acts independent of IGF-1 in bone remains unclear. To define the mode of GH action in bone, we have used a Cre/loxP system in which the type 1 IGF-1 receptor (Igf1r) has been disrupted specifically in osteoblasts in vitro and in vivo. Calvarial osteoblasts from mice homozygous for the floxed IGF-1R allele (IGF-1R(flox/flox)) were infected with adenoviral vectors expressing Cre. Disruption of IGF-1R mRNA (>90%) was accompanied by near elimination of IGF-1R protein but retention of GHR protein. GH-induced STAT5 activation was consistently greater in osteoblasts with an intact IGF-1R. Osteoblasts lacking IGF-1R retained GH-induced ERK and Akt phosphorylation and GH-stimulated IGF-1 and IGFBP-3 mRNA expression. GH-induced osteoblast proliferation was abolished by Cre-mediated disruption of the IGF-1R or co-incubation of cells with an IGF-1-neutralizing antibody. By contrast, GH inhibited apoptosis in osteoblasts lacking the IGF-1R. To examine the effects of GH on osteoblasts in vivo, mice wild type for the IGF-1R treated with GH subcutaneously for 7 days showed a doubling in the number of osteoblasts lining trabecular bone, whereas osteoblast numbers in similarly treated mice lacking the IGF-1R in osteoblasts were not significantly affected. These results indicate that although direct IGF-1R-independent actions of GH on osteoblast apoptosis can be demonstrated in vitro, IGF-1R is required for anabolic effects of GH in osteoblasts in vivo.     

Alterations in dopaminergic modulation of prefrontal cortical acetylcholine release in post-pubertal rats with neonatal ventral hippocampal lesions

Excitotoxic lesion of the ventral hippocampus in neonatal rats is a putative animal model of schizophrenia with characteristic developmental abnormalities in dopaminergic neurotransmission and prefrontal cortical functions. Converging evidence also points to the involvement of the central cholinergic system in neuropsychiatric disorders. These two neurotransmitter systems are interlinked in the prefrontal cortex (PFC) where dopamine stimulates acetylcholine (ACh) release. In the present study, we investigated the role of dopamine in the developmental regulation of prefrontal cortical ACh release and the expression of nicotinic and muscarinic receptors in pre- and post-pubertal rats with neonatal ibotenic acid-induced lesions of the ventral hippocampus (NVH). In vivo microdialysis in the PFC revealed that systemic injections of the D(1)-like receptor agonist (+/-)-6-chloro-7,8-dihydroxy-1-phenyl2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) (2.5 and 5.0 mg/kg i.p.) caused significantly higher ACh release in post-pubertal NVH-lesioned animals (250 and 300% baseline for 2.5 and 5.0 mg/kg, respectively) compared with post-pubertal shams (150 and 220% baseline for 2.5 and 5.0 mg/kg, respectively). Most interestingly, while prefrontal cortical perfusion of SKF 81297 (100 and 250 microM) had no significant effect on ACh release in post-pubertal sham-operated animals, it significantly stimulated ACh release to approximately 250% baseline at both doses in post-pubertal NVH-lesioned animals. Receptor autoradiography demonstrated a significant and selective increase in M(1)-like receptor binding sites in the infralimbic area of the PFC in the post-pubertal NVH-lesioned animals. For all experiments, significant differences between sham and NVH-lesioned animals were observed only in post-pubertal rats. These results suggest a developmentally specific reorganization of the prefrontal cortical cholinergic system involving D(1)-like receptors in the NVH model.     

Effects of immunization of heifers against estradiol on growth, reproductive traits, and carcass characteristics

An experiment was performed to evaluate the effects of active immunization of heifers against estradiol on feedlot performance (growth and efficiency), carcass characteristics, and reproductive functions. Seventy-two crossbred heifers were divided into four equal treatment groups consisting of controls, ovariectomized heifers, and heifers actively immunized against keyhole limpet-estradiol antigen and bovine serum albumin-estradiol antigen. Heifers were fed ad libitum for 170 days. Both groups of heifers immunized against estradiol had higher (P less than 0.05) average daily gains than controls. Heifers immunized against bovine serum albumin-estradiol had increased feed efficiency (P less than 0.05) over controls. Ovariectomized heifers did not perform at levels sufficient to compensate for the initial setback from surgery. No differences were noted in carcass grade, quality, or concentration of water, fat, or protein. Uterine weights were increased in estrogen-immunized animals but were not significantly greater than controls. Ovarian weights and numbers of large follicles (greater than 9 mm diam) in immunized animals were significantly greater than in controls. Twenty-eight percent of the animals (n = 5) in the bovine serum albumin-estradiol-immunized group had cystic follicles (greater than 20 mm diam) and 50% (n = 9) of this group had no detectable corpus luteum. Low titer (1:100) systemic binding of estrogens may act as a steroid reservoir in which systemic estrogen clearance is decreased and availability to target tissues is increased.     

Synergy between PI3K/Akt and Raf/MEK/ERK pathways in IGF-1R mediated cell cycle progression and prevention of apoptosis in hematopoietic cells

The insulin like growth factor-1 (IGF-1) receptor (R) induced PI3K/Akt signal transduction cascade has critical roles in prevention of apoptosis and regulation of cell cycle progression. Here, we discuss the effects of IGF-1R-mediated signal transduction on hematopoietic cells which normally require interleukin-3 (IL-3) for growth and prevention of apoptosis. Cytokine-dependent FDC-P1 hematopoietic cells were conditionally transformed to grow in response to overexpression of IGF-1R in the presence of IGF-1. When these cells were deprived of IL-3 or IGF-1 for 24 hrs, they exited the cell cycle, activated caspase 3 and underwent apoptosis. The effects of inhibitors which targeted the PI3K/Akt and Raf/MEK/ERK pathways were determined. When the cells were cultured with IGF-1 and either PI3K or MEK inhibitors, cell cycle progression and DNA synthesis were inhibited and caspase 3 activity and apoptosis were induced. Coinhibition of both pathways synergized to prevent cell cycle progression, inhibit DNA synthesis and induce apoptosis. These inhibitors had more apoptotic inducing effects when the cells were grown in response to IGF-1 than IL-3, indicating that IL-3 can induce additional anti-apoptotic pathways. These results demonstrate that the PI3K/Akt and Raf/MEK/ERK pathways are intimately involved in IGF-1R-mediated cell cycle progression and prevention of apoptosis in hematopoietic cells.     

Influence of growth and athletic training on heart and lung functions.

Studies were performed at rest and during exercise of varied intensity on 52 boys of pre- and post-pubescent age. Each age group consisted of boys who were engaged in a strenuous prolonged hockey training program; this group was compared with a matched control group who did not participate in a regular training program. Any differences observed in the measured lung functions could be explained on the basis of physical size. Relationship of pulmonary capillary blood flow (Qc) and pulmonary diffusing capacity (DLco) to oxygen consumption were similar to those reported for adults and no difference between the trained and control groups was found in either the pre- or post-pubertal aged boys. Similarily, the trained pre-pubertal boys did not differ significantly from their matched control group in respect to the relationships of heart rate (HR) and stroke volume (SV) for any level of oxygen consumption. In contrast, the post-pubertal trained boys had significantly lower HR and higher SV (P less than 0.01) at each level of work than the control group. These differences between the trained and control post-pubertal boys are consistent with training effects observed in adults. The lack of differences between the trained and control pre-pubertal groups was surprising. Whether the differences in the post-pubertal groups due to a detraining effect in the post-pubertal control boys (as compared to the pre-pubertal control group) or to a continued high level of physical activity during and after the on-set of puberty in trained boys cannot be answered by this study. The findings suggest the importance of high intensity exercise programs during the growth period of adolescence if the efficiency of the oxygen delivery system, and possibly its ultimate dimensions, are to be enhanced.