Insulin-like Growth Factor-1 Gene Expression Research Articles

Jinmaitong, a Traditional Chinese Compound Prescription, Ameliorates the Streptozocin-Induced Diabetic Peripheral Neuropathy Rats by Increasing Sciatic Nerve IGF-1 and IGF-1R Expression.

Jinmaitong (JMT) is a Traditional Chinese Compound Prescription for the treatment of diabetic peripheral neuropathy (DPN). This study aims to investigate the effect of JMT on the insulin-like growth factor 1 (IGF-1) and the insulin like growth factor 1 receptor (IGF-1R) expression in sciatic nerves of diabetic rats. Firstly, the chemical profile of JMT was characterized by UPLC/Q-TOF-MS analysis. A total of 72 compounds were putatively identified. Secondly, streptozotocin (STZ)-induced diabetic rats were treated with neurotropin (NTP, 2.67 NU/kg/day) or JMT at low-dosage (0.4375 g/kg/day), medium-dosage (0.875 g/kg/day), and high-dosage (1.75 g/kg/day) for continuous 16 weeks. Blood glucose and body weight were detected every 4 weeks during the experiment. The mechanical pain and morphological change on sciatic nerves were detected by pain measurement instrument and microscopy. The IGF-1 level in serum and tissues were measured though ELISA and immunohistochemistry. The mRNA and protein expressions of IGF-1, IGF-1R, peripheral myelin protein zero (P0), and peripheral myelin protein 22 (PMP22) in the tissues were measured by qRT-PCR and western blot. As a result, JMT had no significant effect on body weight, but reduced the fasting blood glucose levels of diabetic rats. Besides, the pathological morphology, mechanical pain thresholds, serum level and tissue expression of IGF-1, mRNA, and protein levels of IGF-1R, P0, and PMP22 were significantly improved in JMT group at middle dosage. In conclusion, JMT could ameliorate the behavioristics and morphology changes in DPN rats by promoting IGF-1 and IGF-1R gene and protein expressions in sciatic nerves, as well as regulating the peripheral nerve remyelination genes P0 and PMP22 expressions, which provides scientific evidence for the clinical application of JMT in DPN patients.

Nonadditive and allele-specific expression of insulin-like growth factor 1 in Nile tilapia (Oreochromis niloticus, ♀) × blue tilapia (O. aureus, ♂) hybrids.

Hybrid Nile tilapia (Oreochromis niloticus, ♀) × blue tilapia (O. aureus, ♂) is a widely cultured tilapia variety due to its growth vigor compared to the parent species. As a peptide hormone, insulin-like growth factor 1 (IGF-1) plays a critical role in regulating somatic growth. The present study focuses on the expression characteristics of IGF-1 in hybrid tilapia. The cloned complete open reading frame of IGF-1 in hybrid tilapia is 549 bp in length, encoding a protein of 182 amino acids. The deduced protein is highly similar to that of Nile tilapia and blue tilapia. IGF-1 was found to be primarily expressed in the liver and muscle in the hybrid; lower expression levels were found in other tissues such as the intestine, spleen, and head-kidney. Increased mRNA expression was observed in the liver and muscle of the hybrid compared to Nile tilapia and blue tilapia, indicating a nonadditive expression pattern in the hybrid. An IGF-1 SNP site (397 site: C in Nile tilapia, G in blue tilapia) for differentiating the Nile tilapia or blue tilapia subgenome in hybrids was identified. Pyrosequencing analysis of the liver transcriptome indicated that most of the hybrids (9 of 10 individuals) predominantly expressed the G allele, demonstrating bias of the blue tilapia subgenome. The present study provides novel data indicating, for the first time, overall gene expression of IGF-1 and allele-specific expression in hybrid tilapia.

Resveratrol reduces the expression of insulin-like growth factor-1 and hepatocyte growth factor in stromal cells of women with endometriosis compared with nonendometriotic women.

Resveratrol, a phytoalexin polyphenol, has antiproliferative, antiangiogenic, anti-inflammatory, and antioxidant properties. The present study has assessed the effect of resveratrol treatment on the expression of insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) in endometrial stromal cells (ESCs) from women with and without endometriosis. Endometrial tissues were obtained from 40 endometriotic patients and 15 nonendometriotic control women. After the enzymatic digestion, 13 eutopic ESCs (EuESCs), 8 ectopic ESCs (EESCs), and 11 control ESCs (CESCs) were treated with resveratrol (100μM) for 6, 24, and 48hr. The gene and protein expressions of IGF-1 and HGF were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay methods, respectively. Results showed that resveratrol treatment decreased significantly the gene expression of IGF-1 and HGF in EuESCs, EESCs, and CESCs (p<0.05). The effect of resveratrol treatment on the reduction of IGF-1 gene expression was statistically more noticeable in EESCs compared with CESCs (p<0.05). Also, in the case of HGF gene expression, the reducing effect of resveratrol treatment was statistically more considerable in EESCs compared with EuESCs and CESCs (p<0.05 and p<0.01, respectively). The IGF-1 and HGF protein production decreased significantly in EuESCs and EESCs (p<0.05) but not in CESCs. These findings suggest that resveratrol treatment could reduce the expression of IGF-1 and HGF in ESCs especially in EESCs, which play a pivotal role in disease progression.

Expression Patterns of Growth Related Genes in Juvenile Red Spotted Grouper (Epinephelus akaara) with Different Growth Performance after Size Grading.

Fish shows great difference in growth rate between individuals during larval development and early growth. This difference seriously reduces the production efficiency in fish culture. Growth hormone (GH)/Insulin-like growth factor 1 (IGF1) system is said to play some pivotal roles in fish growth. In this study, we investigated differences of GH, IGF1 and GHR gene expressions in juvenile red spotted grouper (Epinephelus akaara) with different growth performance. Red spotted groupers were reared under the same environmental condition (water temperature 24±1℃, natural light) for 96 days after hatching. They were divided into 3 groups by size (fast growing, middle growing and slow growing groups: FGG, MGG, and SGG, respectively). RNA was extracted from the brain, liver and muscle tissues from each group, and target gene expression was examined by real-time PCR. In the brain with pituitary gland, expression of GH gene in FGG was significantly higher than the expression in SGG, but the expression of IGF1 and GHR genes in the muscle was highest in SGG. Difference of GHR and IGF1 mRNA in the liver between groups with different growth performance was less clear than that in other tissues, although level of IGF1 mRNA was higher in SGG than in MGG. These results suggest that hormonal governing of growth is not the same in fast growing and slow growing fish, and size grading could cause a shift of hormonal state and growth pattern in this species.

Quantifying promoter-specific Insulin-like Growth Factor 1 gene expression by interrogating public databases.

The actions of insulin‐like growth factor 1 (IGF1), a small, secreted protein, are essential for normal somatic growth in children and are important for tissue regeneration and repair in adults. Similar functions are conserved in other mammalian species. IGF1 gene regulation is complicated in mammals, with transcription being controlled by different hormonal, nutritional, and tissue‐specific inputs. Quantifying IGF1 gene expression in different organs and tissues also has been difficult because of the variable contributions of its two promoters and because of the lack of standard platforms for analysis. Here, I have taken advantage of the wealth of information found in publicly accessible RNA‐sequencing libraries to measure steady‐state levels of IGF1 mRNAs from human and macaque, species chosen because they are not readily tractable experimental organisms, yet retain similar IGF1 gene organization. Results demonstrate that IGF1 transcripts are highly expressed in fat and liver in both species, and are induced during human adipocyte differentiation. IGF1 mRNAs also are increased in macaque skeletal muscle after selected dietary manipulations. In the organs and tissues examined, IGF1 promoter 1 appears to be far more active than promoter 2. Collectively, these observations show that interrogating large‐scale public genomic resources is an effective strategy for quantifying gene expression across different tissues and species.

Effect of Recombinant Insulin-like Growth Factor-2 Injected into the Hippocampus on Memory Impairment Following Hippocampal Intracerebral Hemorrhage in Rats

Background: Insulin-like growth factor 2 (IGF-2) is a growth factor and an anti-inflammatory cytokine that plays a pivotal role in memory. In this study, we examined the effect of recombinant IGF-2 on memory impairment due to intracerebral hemorrhage (ICH). Avoidance and recognition memory, locomotor activity, neurological deficit score (NDS), and the level of the IGF-2 gene expression were evaluated. Materials and Methods: To induce ICH, 100 μL of autologous blood was injected into the left hippocampus of male Sprague Dawley rats. Recombinant IGF-2 was injected into the damaged hippocampus 30 minutes after the induction of ICH. Then, over two weeks, NDS, locomotor activity, passive avoidance, and novel object recognition (NOR) test were evaluated. Finally, the level of IGF-2 gene expression was evaluated by using the real-time polymerase chain reaction technique. Result: Our results indicated that recombinant IGF-2 injection significantly increased step-through latency (P&lt;0.001) and total time spent in the dark box (P&lt;0.01). However, no significant difference was seen in recognition memory and NDS. Locomotor activity did not significantly change in any group. A significantly reduced level of IGF-2 was observed after two weeks (P&lt;0.05). Conclusion:The results of this study show that a single dose of recombinant IGF-2 injection can influence hippocampus-dependent memories. Importantly, IGF-2 did not change locomotor activity and NDS after two weeks, which probably represents its specific function in memory.[GMJ.2018;7:e1353]

Effect of Recombinant Insulin-like Growth Factor-2 Injected into the Hippocampus on Memory Impairment Following Hippocampal Intracerebral Hemorrhage in Rats.

Background: Insulin-like growth factor 2 (IGF-2) is a growth factor and an anti-inflammatory cytokine that plays a pivotal role in memory. In this study, we examined the effect of recombinant IGF-2 on memory impairment due to intracerebral hemorrhage (ICH). Avoidance and recognition memory, locomotor activity, neurological deficit score (NDS), and the level of the IGF-2 gene expression were evaluated. Materials and Methods: To induce ICH, 100 μL of autologous blood was injected into the left hippocampus of male Sprague Dawley rats. Recombinant IGF-2 was injected into the damaged hippocampus 30 minutes after the induction of ICH. Then, over two weeks, NDS, locomotor activity, passive avoidance, and novel object recognition (NOR) test were evaluated. Finally, the level of IGF-2 gene expression was evaluated by using the real-time polymerase chain reaction technique.Result: Our results indicated that recombinant IGF-2 injection significantly increased step-through latency (P<0.001) and total time spent in the dark box (P<0.01). However, no significant difference was seen in recognition memory and NDS. Locomotor activity did not significantly change in any group. A significantly reduced level of IGF-2 was observed after two weeks (P<0.05). Conclusion: The results of this study show that a single dose of recombinant IGF-2 injection can influence hippocampus-dependent memories. Importantly, IGF-2 did not change locomotor activity and NDS after two weeks, which probably represents its specific function in memory.

Effect of Recombinant Insulin-like Growth Factor-2 Injected into the Hippocampus on Memory Impairment Following Hippocampal Intracerebral Hemorrhage in Rats

Background: Insulin-like growth factor 2 (IGF-2) is a growth factor and an anti-inflammatory cytokine that plays a pivotal role in memory. In this study, we examined the effect of recombinant IGF-2 on memory impairment due to intracerebral hemorrhage (ICH). Avoidance and recognition memory, locomotor activity, neurological deficit score (NDS), and the level of the IGF-2 gene expression were evaluated. Materials and Methods: To induce ICH, 100 μL of autologous blood was injected into the left hippocampus of male Sprague Dawley rats. Recombinant IGF-2 was injected into the damaged hippocampus 30 minutes after the induction of ICH. Then, over two weeks, NDS, locomotor activity, passive avoidance, and novel object recognition (NOR) test were evaluated. Finally, the level of IGF-2 gene expression was evaluated by using the real-time polymerase chain reaction technique. Result: Our results indicated that recombinant IGF-2 injection significantly increased step-through latency (P&lt;0.001) and total time spent in the dark box (P&lt;0.01). However, no significant difference was seen in recognition memory and NDS. Locomotor activity did not significantly change in any group. A significantly reduced level of IGF-2 was observed after two weeks (P&lt;0.05). Conclusion:The results of this study show that a single dose of recombinant IGF-2 injection can influence hippocampus-dependent memories. Importantly, IGF-2 did not change locomotor activity and NDS after two weeks, which probably represents its specific function in memory.[GMJ.2018;7:e1353]

Expression of insulin-like growth factor 1 and its receptor in preovulatory follicles and in the corpus luteum in the bitch

In the bitch, ovarian follicular and corpus luteum (CL) development and function are regulated by gonadotropins as well as local factors, the role of which is especially important during the early CL phase of relative gonadotrophic independence. We assumed that insulin-like growth factor 1 (IGF1) has a paracrine/autocrine regulatory role in ovarian follicular and luteal function in the dog. To address our hypothesis, we studied gene and protein expression of IGF1 and its receptor (IGF1R) in preovulatory follicles and in the CL of pregnant and non-pregnant dogs, and following antigestagen (aglepristone, progesterone receptor blocker) treatment in mid-gestation. Ovaries in the follicular phase were collected from five bitches. CL were collected on pregnancy Days 8–12 (pre-implantation), 18–25 (post-implantation), 35–40 (mid-gestation), at prepartum luteolysis, and 24 h and 72 h after aglepristone treatment in mid-gestation (n = 3–5 per group). From non-pregnant bitches, CL were collected on Days 5, 15, 25, 35, 45, 65 after ovulation (n = 4–5 per group). Semi-quantitative real-time (TaqMan) PCR and immunohistochemistry were applied. IGF1 immunostaining in preovulatory follicles seemed stronger in theca interna than granulosa cells. IGF1R signals appeared more intense in granulosa cells at the apical part of mural folds. In pregnant dogs, luteal IGF1 mRNA expression decreased significantly from pre-implantation to prepartum luteolysis, while IGF1R expression increased at prepartum luteolysis. Aglepristone treatment in mid-gestation had no effect on IGF1 and IGF1R mRNA levels. In non-pregnant bitches, highest IGF1 mRNA concentrations were found in the early CL and decreased by Days 45 and 65, while IGF1R expression did not change. In the CL of pregnant bitches, signals for IGF1 and IGF1R in luteal cells were strongest at pre- and post-implantation and weakest at prepartum luteolysis. IGF1 and IGF1R immunostaining was also detected in macrophages and in blood vessels. In conclusion, IGF1 may have a paracrine or autocrine role in granulosa and theca interna cells in preovulatory follicles. As IGF1 was highest represented in early luteal stages in pregnant and non-pregnant bitches, this may support a role for IGF1 in steroid synthesis, angiogenesis and cell proliferation as well as in immune function in the early canine CL. The unaffected mRNA levels after aglepristone treatment may support that IGF1 is not directly regulated by local progesterone in an auto- or paracrine manner.

Effects of estradiol and progesterone on secretion of epidermal growth factor and insulin-like growth factor-1 in cultured yak endometrial epithelial cells.

We isolated and purified yak (Bos grunniens) endometrial epithelial cells and assayed different concentrations of estradiol (E2) and progesterone (P4) with respect to secretion of epidermal growth factor (EGF) and insulin-like growth factor-1 (IGF-1). Uterine epithelia were confirmed with Feulgen staining, karyotype analysis, and immunohistochemistry. Then, cells were treated with E2 and P4 and cultured in serum-free medium for 24 h. EGF and IGF-1 were measured with immunofluorescence, Real-time PCR (RT-PCR), Western blot (WB), and ELISA. When E2 and P4 were applied separately, the expression of EGF and IGF-1 did not change significantly, and EGF and IGF-1 gene and protein expression and epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor (IGFR) gene expression were significantly increased when both hormones were combined. When the hormones were used singly, the optimal concentration of E2 was 10 ng/mL and of P4 was 100 ng/mL. When combined, the optimal E2 concentration was 10 ng/mL and P4 was 10 ng/mL. Thus, E2 and P4 can modulate expression of EGF and IGF-1 in endometrial epithelial cells at the morphological, gene, protein, and exocrine level, which is of great significance to improve the rate of yak embryo implantation and reproduction.

Diversification of the insulin-like growth factor 1 gene in mammals

Insulin-like growth factor 1 (IGF1), a small, secreted peptide growth factor, is involved in a variety of physiological and patho-physiological processes, including somatic growth, tissue repair, and metabolism of carbohydrates, proteins, and lipids. IGF1 gene expression appears to be controlled by several different signaling cascades in the few species in which it has been evaluated, with growth hormone playing a major role by activating a pathway involving the Stat5b transcription factor. Here, genes encoding IGF1 have been evaluated in 25 different mammalian species representing 15 different orders and ranging over ~180 million years of evolutionary diversification. Parts of the IGF1 gene have been fairly well conserved. Like rat Igf1 and human IGF1, 21 of 23 other genes are composed of 6 exons and 5 introns, and all 23 also contain recognizable tandem promoters, each with a unique leader exon. Exon and intron lengths are similar in most species, and DNA sequence conservation is moderately high in orthologous exons and proximal promoter regions. In contrast, putative growth hormone-activated Stat5b-binding enhancers found in analogous locations in rodent Igf1 and in human IGF1 loci, have undergone substantial variation in other mammals, and a processed retro-transposed IGF1 pseudogene is found in the sloth locus, but not in other mammalian genomes. Taken together, the fairly high level of organizational and nucleotide sequence similarity in the IGF1 gene among these 25 species supports the contention that some common regulatory pathways had existed prior to the beginning of mammalian speciation.

Effects of l-arginine on growth hormone and insulin-like growth factor 1.

l-Arginine has been reported to promote cellular and organismal growth. In this study, the effects of l-arginine on the expression of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), the two key growth factors, are investigated in cultured GH3 pituitary epithelium and HepG2 cells, respectively. l-Arginine significantly induced the gene expression of GH and IGF-1 in GH3 pituitary epithelium and HepG2 hepatocytes respectively, and reduced IGF binding protein-1 gene expression in HepG2 cells assessed via quantitative polymerase chain reaction analysis. l-Arginine also significantly induced GH and IGF-1 hormone secretion from GH3 and HepG2 cells, respectively. In addition, the multi-target ELISA analysis conducted revealed that phosphorylation of p-38 MAPK, MEK, and JNK were significantly increased in HepG2 cells, suggesting l-arginine-induced activation of the MAPK signaling pathway. These results suggest that l-arginine promotes the synthesis and secretion of GH and IGF-1 in vitro and induces the MAPK signaling cascade in cultured hepatocytes.

Gene expression of insulin receptor, insulin-like growth factor increases and insulin-like growth factor-binding protein-3 reduces with increase in prostate size in benign prostatic hyperplasia

Introduction: Although the role of insulin in the development of benign prostatic hyperplasia (BPH) is well established, there are no studies regarding alteration in the gene expression of components of insulin-signaling pathway and their association with prostate size in BPH. Hence, the study was designed to analyze the gene and protein expression of insulin receptor and its related components in patients with BPH.Materials and methods: Twenty-seven BPH patients aged between 55 and 75 years were recruited in the study and prostatic tissues were obtained after transurethral resection of the prostate. Gene expression levels of Insulin receptor (IR), insulin receptor substrate (IRS), insulin-like growth factor (IGF) and insulin-like growth factor-binding protein-3 (IGFBP-3) were assessed by q-PCR.Results: Insulin receptor (IR-A and B) and insulin-like growth factors (IGF-1 and IGF-2) gene expression were significantly increased and IGFBP-3 gene expression was reduced in BPH patients with larger prostate size. Also, serum insulin was significantly increased and IGFBP-3 was significantly reduced in patients with larger prostate size.Conclusion: Increased expression of IR-A, B and IGF-1, 2 genes and reduced IGFBP-3 gene expression was associated with larger prostate size in BPH.

Hypothermia Regulates Insulin-like Growth Factor 1 Gene Expression in PC12 Cells

In this study, we evaluated the effects of various hypothermic conditions (32℃), including lithium chloride treatment, on insulin-like growth factor 1 (IGF-1) gene expression in PC12 cells. The results show that short-term hypothermic treatment ( 1 day). Repeated switching between normal temperature and hypothermia every 2 h increased IGF-1 gene expression approximately 3-4-fold. These findings indicate that hypothermia dynamically regulates IGF-1 gene expression. This study could be helpful for the development of treatment and diagnostic strategies for ischemia.

Maternal betaine supplementation in rats induces intergenerational changes in hepatic IGF-1 expression and DNA methylation.

Betaine is widely used in animal nutrition to promote growth. Here, we aimed to investigate whether maternal betaine supplementation during pregnancy can exert multigenerational effects on growth across two generations and the possible epigenetic modifications associated to such effects. In this study, 3-month-old female Sprague-Dawley rats were fed diet supplemented with 1% betaine throughout the pregnancy and lactation. Betaine-supplemented dams produced bigger litter but smaller F1 pups at birth and weaning. However, F2 pubs had higher weaning weight. In accordance with the growth performance, serum insulin-like growth factor 1 (IGF-1) levels were significantly lower in F1 yet higher in F2 pups, so was hepatic IGF-1 mRNA expression. Concurrently, dietary betaine supplementation to F0 dams increased hepatic expression of betaine homocysteine methyltransferase, at both mRNA and protein levels, in F1, but not F2 pups. Moreover, hepatic IGF-1 gene promoter 1 was detected to be significantly hypermethylated in F1 pups, whereas both promoters 1 and 2, together with almost all exons, were found to be hypomethylated in F2 offspring. Maternal betaine supplementation during pregnancy and lactation exerts distinct effects on growth of F1 and F2 rat offspring, probably through differential modification of IGF-1 gene methylation and expression in liver.

Dietary protein-induced hepatic IGF-1 secretion mediated by PPARγ activation.

Dietary protein or amino acid (AA) is a crucial nutritional factor to regulate hepatic insulin-like growth factor-1 (IGF-1) expression and secretion. However, the underlying intracellular mechanism by which dietary protein or AA induces IGF-1 expression remains unknown. We compared the IGF-1 gene expression and plasma IGF-1 level of pigs fed with normal crude protein (CP, 20%) and low-protein levels (LP, 14%). RNA sequencing (RNA-seq) was performed to detect transcript expression in the liver in response to dietary protein. The results showed that serum concentrations and mRNA levels of IGF-1 in the liver were higher in the CP group than in the LP group. RNA-seq analysis identified a total of 1319 differentially expressed transcripts (667 upregulated and 652 downregulated), among which the terms “oxidative phosphorylation”, “ribosome”, “gap junction”, “PPAR signaling pathway”, and “focal adhesion” were enriched. In addition, the porcine primary hepatocyte and HepG2 cell models also demonstrated that the mRNA and protein levels of IGF-1 and PPARγ increased with the increasing AA concentration in the culture. The PPARγ activator troglitazone increased IGF-1 gene expression and secretion in a dose dependent manner. Furthermore, inhibition of PPARγ effectively reversed the effects of the high AA concentration on the mRNA expression of IGF-1 and IGFBP-1 in HepG2 cells. Moreover, the protein levels of IGF-1 and PPARγ, as well as the phosphorylation of mTOR, significantly increased in HepG2 cells under high AA concentrations. mTOR phosphorylation can be decreased by the mTOR antagonist, rapamycin. The immunoprecipitation results also showed that high AA concentrations significantly increased the interaction of mTOR and PPARγ. In summary, PPARγ plays an important role in the regulation of IGF-1 secretion and gene expression in response to dietary protein.

Different expression of leptin and IGF1 in the adult and prepubertal testis in dogs

Leptin (Lep) and insulin-like growth factor 1 (IGF1) are implicated in the regulation of testicular function, but in dogs, our knowledge is limited to the possible role of the IGF1 system in testicular tumours. In this study, we aimed to describe and compare gene expression and protein localization of Lep, IGF1 and their receptors (LepR and IGF1R, respectively) in the testis of healthy adult and prepubertal dogs. Testes were collected from sexually healthy mature (n=7) and from 8-week-old dogs (n=7). Relative gene expression of Lep, LepR, IGF1 and IGF1R was determined by semi-quantitative real-time (TaqMan) PCR and cellular distribution in the testis by immunohistochemistry. Statistical analysis was carried out with Student's t test. Lep and LepR mRNA concentration was similar between the two groups, but IGF1 and IGF1R gene expression was significantly higher in the 8-week-old pups. Protein localization and the intensity of signals differed by age. In adults, Lep and LepR immunoreactivity was detected in spermatocytes and spermatids. Leydig cells showed sporadic, weak Lep staining. In prepubertal animals, intense Lep signals were present in Leydig and Sertoli cells, and LepR was found in Leydig cells. IGF1 and IGF1R protein was expressed in spermatogonia of the mature testis; IGF1 signals in Leydig cells seemed stronger than IGF1R. In the pups, IGF1 and IGF1R staining was detected in Leydig cells and in gonocytes. Sertoli cells showed weak IGF1 and sporadic, weak IGF1R signals. In conclusion, Lep and IGF1 may support spermatogenesis in adult dogs and mediate Leydig cell function. In the immature testis, they may promote development of Sertoli and Leydig cells and gonocytes.

Resistance Training Alters the Proportion of Skeletal Muscle Fibers but Not Brain Neurotrophic Factors in Young Adult Rats.

Antonio-Santos, J, Ferreira, DJS, Gomes Costa, GL, Matos, RJB, Toscano, AE, Manhães-de-Castro, R, and Leandro, CG. Resistance training alters the proportion of skeletal muscle fibers but not brain neurotrophic factors in young adult rats. J Strength Cond Res 30(12): 3531–3538, 2016—Resistance training (RT) is related to improved muscular strength and power output. Different programs of RT for rats have been developed, but peripheral and central response has not been evaluated directly in the same animal. To test the hypothesis that RT induces central and peripheral adaptations, this study evaluated the effects of a RT on the performance of a weekly maximum overload test, fiber-type typology, and brain neurotrophic factors in young adult rats. Thirty-one male Wistar rats (65 ± 5 days) were divided in 2 groups: nontrained (NT, n = 13) and trained (T, n = 18). Trained group was submitted to a program of RT ladder climbing, gradually added mass, 5 days per week during 8 weeks at 80% of individual maximum overload. This test was weekly performed to adjust the individual load throughout the weeks for both groups. After 48 hours from the last session of exercise, soleus and extensor digital longus (EDL) muscles were removed for myofibrillar ATPase staining analysis. Spinal cord, motor cortex, and cerebellum were removed for RT-PCR analysis of BDNF and insulin-like growth factor-1 (IGF-1) gene expression. In EDL muscle, T animals showed an increase in the proportion of type IIb fibers and a reduction of type IIa fibers. Insulin-like growth factor-1 gene expression was reduced in the cerebellum of T animals (NT: 1.025 ± 0.12; T: 0.57 ± 0.11). Our data showed that 8 weeks of RT were enough to increase maximum overload capacity and the proportion of glycolytic muscle fibers, but there were no associations with the expression of growth neurotrophic factors.

Insulin-like Growth Factor 1 gene polymorphism and breast cancer risk.

Insulin-like Growth Factor-1 (IGF-1) gene polymorphism has been associated with an increased risk for breast cancer. IGF-1 is a key regulator of proliferation, cell differentiation and apoptosis. It has important mitogenic and anti-apoptotic activities in normal cells and in breast cancer cells, acting synergistically with estrogen to increase neoplastic cell proliferation. This review aims to present the recent finds of IGF-1 gene polymorphism and its relationship with the risk of breast cancer through following the polymorphic dinucleotide repeat cytosine-adenine (CA) and single nucleotide polymorphisms (SNPs) by searching in the PubMed database publications focused studies published from 2010 to 2015 related to IGF-1 gene polymorphism and breast cancer risk. A growing number of studies support an association between IGF-1 gene polymorphism and breast cancer risk with conflicting results, nevertheless elucidation of the patterns of IGF-1 gene expression may permit characterization of women at high-risk for breast cancer, as well as the development of strategies for early diagnosis and efficient treatment against the disease.

Supplementation with Lactobacillus rhamnosus SP1 normalises skin expression of genes implicated in insulin signalling and improves adult acne.

Systemic supplementation with probiotics is increasingly being explored as a potential treatment strategy for skin disorders. Because both the gut-skin axis and dysregulation of insulin signalling have been implicated in the pathogenesis of adult acne, we designed the current study to evaluate the effect of supplementation with the probiotic strain Lactobacillus rhamnosus SP1 (LSP1) on skin expression of genes involved in insulin signalling and acne improvement in adult subjects. A pilot, randomised, double-blinded, placebo-controlled study was conducted with 20 adult subjects (14 females and 6 males; mean age: 33.7±3.3 years) with acne. Over a 12-week period, the probiotic group (n=10) consumed a liquid supplement containing LSP1 at a dose of 3×109 cfu/day (75 mg/day), whereas the placebo group (n=10) received a liquid lacking probiotics. Paired skin biopsies - one obtained before treatment initiation and one obtained at the end of the 12-week treatment period - were analysed for insulin-like growth factor 1 (IGF1) and forkhead box protein O1 (FOXO1) gene expression. The clinical criterion for efficacy was the investigator's global improvement rating on a five-point scale. Compared with baseline, the probiotic group showed a 32% (P<0.001) reduction, as well as a 65% increase (P<0.001) in IGF1 and FOXO1 gene expression in the skin, respectively. No such differences were observed in the placebo group. Patients in the probiotic group had an adjusted odds ratio of 28.4 (95% confidence interval = 2.2-411.1, P<0.05) to be rated by physicians as improved/markedly improved (versus worsened or unchanged) compared with the placebo group. We conclude that supplementation with the probiotic strain LSP1 normalises skin expression of genes involved in insulin signalling and improves the appearance of adult acne.