scholarly journals Central Suppression of the GH/IGF Axis and Abrogation of Exercise-Related mTORC1/2 Activation in the Muscle of Phenotype-Selected Male Marathon Mice (DUhTP)

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3418
Author(s):  
Julia Brenmoehl ◽  
Christina Walz ◽  
Caroline Caffier ◽  
Elli Brosig ◽  
Michael Walz ◽  
...  

The somatotropic axis is required for a number of biological processes, including growth, metabolism, and aging. Due to its central effects on growth and metabolism and with respect to its positive effects on muscle mass, regulation of the GH/IGF-system during endurance exercise is of particular interest. In order to study the control of gene expression and adaptation related to physical performance, we used a non-inbred mouse model, phenotype-selected for high running performance (DUhTP). Gene expression of the GH/IGF-system and related signaling cascades were studied in the pituitary gland and muscle of sedentary males of marathon and unselected control mice. In addition, the effects of three weeks of endurance exercise were assessed in both genetic groups. In pituitary glands from DUhTP mice, reduced expression of Pou1f1 (p = 0.002) was accompanied by non-significant reductions of Gh mRNA (p = 0.066). In addition, mRNA expression of Ghsr and Sstr2 were significantly reduced in the pituitary glands from DUhTP mice (p ≤ 0.05). Central downregulation of Pou1f1 expression was accompanied by reduced serum concentrations of IGF1 and coordinated downregulation of multiple GH/IGF-signaling compounds in muscle (e.g., Ghr, Igf1, Igf1r, Igf2r, Irs1, Irs2, Akt3, Gskb, Pik3ca/b/a2, Pten, Rictor, Rptor, Tsc1, Mtor; p ≤ 0.05). In response to exercise, the expression of Igfbp3, Igfbp 4, and Igfbp 6 and Stc2 mRNA was increased in the muscle of DUhTP mice (p ≤ 0.05). Training-induced specific activation of AKT, S6K, and p38 MAPK was found in muscles from control mice but not in DUhTP mice (p ≤ 0.05), indicating a lack of mTORC1 and mTORC2 activation in marathon mice in response to physical exercise. While hormone-dependent mTORC1 and mTORC2 pathways in marathon mice were repressed, robust increases of Ragulator complex compounds (p ≤ 0.001) and elevated sirtuin 2 to 6 mRNA expression were observed in the DUhTP marathon mouse model (p ≤ 0.05). Activation of AMPK was not observed under the experimental conditions of the present study. Our results describe coordinated downregulation of the somatotropic pathway in long-term selected marathon mice (DUhTP), possibly via the pituitary gland and muscle interaction. Our results, for the first time, demonstrate that GH/IGF effects are repressed in a context of superior running performance in mice.

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 736
Author(s):  
Christina Walz ◽  
Julia Brenmoehl ◽  
Nares Trakooljul ◽  
Antonia Noce ◽  
Caroline Caffier ◽  
...  

It is assumed that crosstalk of central and peripheral tissues plays a role in the adaptive response to physical activity and exercise. Here, we wanted to study the effects of training and genetic predisposition in a marathon mouse model on mRNA expression in the pituitary gland. Therefore, we used a mouse model developed by phenotype selection for superior running performance (DUhTP) and non-inbred control mice (DUC). Both mouse lines underwent treadmill training for three weeks or were kept in a sedentary condition. In all groups, total RNA was isolated from the pituitary gland and sequenced. Molecular pathway analysis was performed by ingenuity pathway analysis (IPA). Training induced differential expression of 637 genes (DEGs) in DUC but only 50 DEGs in DUhTP mice. Genetic selection for enhanced running performance strongly affected gene expression in the pituitary gland and identified 1732 DEGs in sedentary DUC versus DUhTP mice. Training appeared to have an even stronger effect on gene expression in both lines and comparatively revealed 3828 DEGs in the pituitary gland. From the list of DEGs in all experimental groups, candidate genes were extracted by comparison with published genomic regions with significant effects on training responses in mice. Bioinformatic modeling revealed induction and coordinated expression of the pathways for ribosome synthesis and oxidative phosphorylation in DUC mice. By contrast, DUhTP mice were resistant to the positive effects of three-week training on protein and energy metabolism in the pituitary gland.


Reproduction ◽  
2009 ◽  
Vol 137 (1) ◽  
pp. 129-140 ◽  
Author(s):  
J L Crawford ◽  
D A Heath ◽  
L J Haydon ◽  
B P Thomson ◽  
D C Eckery

In eutherian mammals, the gonadotrophins (LH and FSH) are synthesized and stored in gonadotroph cells under the regulation of multiple mechanisms including GnRH. Very little is known about the regulation of gonadotrophin secretion and storage in pituitary glands of marsupials. This study revealed, using quantitative PCR and heterologous RIA techniques, thatLHBmRNA expression levels remained constant over the oestrous cycle, regardless of the presence of a preovulatory LH surge, which is characteristic of a hormone secreted under regulation. Our sampling regime was unable to detect pulses of LH during the follicular phase, althoughGNRHRmRNA levels had increased at this time. Pulses of LH were, however, detected in the luteal phase of cycling females, in anoestrus females and in males. There was a positive correlation between gene expression ofFSHBand plasma levels of FSH at different stages of the oestrous cycle and no pulses of FSH were detected at any time; all characteristics of a hormone secreted via the constitutive pathway. Usingin situhybridisation and immunohistochemistry methods, we determined that mRNA expression ofLHBandFSHB, and protein storage of gonadotrophins exhibited a similar pattern of localisation within the pituitary gland. Additionally, sexual dimorphism of gonadotroph populations was evident. In summary, these findings are similar to that reported in eutherians and considering that marsupial evolution diverged from eutherians over 100 million years ago suggests that the regulation of gonadotrophins is highly conserved indeed.


Reproduction ◽  
2009 ◽  
Vol 137 (1) ◽  
pp. 141-150 ◽  
Author(s):  
Christine Margaret Whitelaw ◽  
Jane Elizabeth Robinson ◽  
George Ballantine Chambers ◽  
Peter Hastie ◽  
Vasantha Padmanabhan ◽  
...  

The neurotransmitters/neuromodulators galanin (GAL) and galanin-like peptide (GALP) are known to operate through three G protein-coupled receptors, GALR1, GALR2 and GALR3. The aim of this study was to investigate changes in expression of mRNA for galanin, GALP and GALR1–3 in the hypothalamus and pituitary gland, of male and female sheep, to determine how expression changed in association with growth and the attainment of reproductive competence. Tissue samples from the hypothalami and pituitary glands were analysed from late foetal and pre-pubertal lambs and adult sheep. Although mRNA for galanin and GALR1-3 was present in both tissues, at all ages and in both genders, quantification of GALP mRNA was not possible due to its low levels of expression. mRNA expression for both galanin and its receptors was seen to change significantly in both tissues as a function of age. Specifically, hypothalamic galanin mRNA expression increased with age in the male, but decreased with age in the female pituitary gland. mRNA expression for all receptors increased between foetal and pre-pubertal age groups and decreased significantly between pre-pubertal and adult animals. The results indicate that the expression of mRNA for galanin and its receptors changes dynamically with age and those significant differences exist with regard to tissue type and gender. These changes suggest that galaninergic neuroendocrine systems could be involved in the regulation of ovine growth and or the development of reproductive competence. The roles played by these systems in the sheep, however, may differ from other species, in particular the neuroendocrine link between nutrition and reproduction and GALR1's role in pituitary signalling.


2014 ◽  
Vol 884-885 ◽  
pp. 615-618 ◽  
Author(s):  
Jing Su ◽  
Cong Ying Wang ◽  
Shen Chen ◽  
Xiao Yuan Zhu

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous enzyme in glycolysis that catalyzes an important energy-yielding step in carbohydrate metabolism in the cytoplasm. Independent of its glycolytic activity, evident shown that GAPDH playing roles in several non-metabolic processes such as control of gene expression in response to various stimuli. Moreover it has been shown to be regulated at the transcriptional levels in response to various stimuli, including ROS-triggered responses. In this study, we demonstrated that the mRNA expression of a cytoplasm GAPDH (GAPC2) in response to blast infection in rice leave. The result suggested that the expression of this gene may relative to the disease resistance.


2010 ◽  
Vol 22 (1) ◽  
pp. 282
Author(s):  
R. A. Satrapa ◽  
R. A. L. Simões ◽  
A. C. S. Castilho ◽  
T. Nabhan ◽  
C. F. Silva ◽  
...  

There is evidence that IGF system can be involved in the oocyte competence and, consequently, in the embryo development. To better understand possible differences between Bos taurus and Bos indicus in in vitro embryo development, the current work aimed to assess the expression of IGF ligands (IGF-1 and 2), types 1 and 2 IGF receptors (IGFR1 and 2), IGF-binding proteins 2 and 4 (IGFBP-2 and 4), and type A pregnancy-associated plasmatic protein (PAPP-A) mRNA in bovine immature oocytes fromBos Taurus and Bos indicus. Nellore and Holstein cows were submitted to ovum pickup, and the oocytes with grade 1, 2, and 3 were selected. To remove cumulus cells and pellucida zone, respectively, the oocytes were submitted to vortex (900 × g for 3 min) and protease treatment (Protease® from Streptomyces griseus, Sigma-Aldrich Corporation, St. Louis, MO, USA). Pools of 20 oocytes obtained from Nellore (n = 8) and Holstein (n = 4) cows were submitted to total RNA extraction (RNeasy, Qiagen, Valencia, CA, USA). The gene expression of target genes was measured by real-time RT-PCR with oligo-dT in the RT and bovine-specific primers in the PCR. Expression of cyclophlin A (CYC-A) was used as internal control. The means of mRNA levels of target genes between the breeds were compared using t-test and Mann-Whitney test when the data had normal or not normal distribution, respectively. The means values of mRNA expression of IGF-1, IGF-2, IGF receptors (1 and 2), and IGFBP 2 and 4 were greater in Holstein (0.96 ± 0.21, 0.74 ± 0.27, 1.08 ± 0.04, 1.19 ± 0.5, 1.21 ± 0.23, 0.53 ± 0.15, respectively) compared with Nellore (0.48 ± 0.10, 0.07 ± 0.02, 0.04 ± 0.03, 0.06 ± 0.02, 0.05 ± 0.01, 0.03 ± 0.15, respectively; P < 0.01). Never- theless, mRNA expression of PAPP-A was much greater in Nellore (28.10 ± 18.96) than in Holstein (1.32 ± 0.17; P < 0.05). These results suggest that high expression of PAPP-A and low expression of IGFBP-2 and 4 could allow more efficiency on the degradation of IGFBP and increase the IGF bioavailability in the oocytes from Nellore as compared with Holstein cows. Satrapa, Simões, and Castilho received a fellowship and funding from FAPESP (São Paulo, Brazil).


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Wen Zhang ◽  
Wenjing Yu ◽  
Daohan Wang ◽  
Li Wei ◽  
Minkyoung Lee ◽  
...  

The purpose of this study was to explore the positive effects of Jian-Pi-Zhi-Dong Decoction (JPZDD) on Tourette syndrome (TS) by investigating the expression of gamma-aminobutyric acid (GABA) and its type A receptor (GABAAR) in the striatum of a TS mice model. The model was induced by 3,3′-iminodipropionitrile (IDPN) treatment; then mice were divided into 4 groups (n=22, each); control and IDPN groups were gavaged with saline and the remaining 2 groups were gavaged with tiapride and JPZDD. We recorded the stereotypic behaviors of TS mice and measured the content of GABA in striatum by HPLC and GABAAR expression by immunohistochemistry and real-time PCR. Our results showed that JPZDD inhibited the abnormal behaviors of TS model mice and decreased GABA levels and GABAAR protein and mRNA expression in the striatum of TS model mice. In brief, the mechanism by which JPZDD alleviates TS symptoms may be associated with GABAAR expression downregulation in striatum which may regulate GABA metabolism.


2007 ◽  
Vol 194 (1) ◽  
pp. 31-40 ◽  
Author(s):  
E A Parker ◽  
A Hegde ◽  
M Buckley ◽  
K M Barnes ◽  
J Baron ◽  
...  

Previous studies of the GH–IGF system gene expression in growth plate using immunohistochemistry and in situ hybridization have yielded conflicting results. We therefore studied the spatial and temporal patterns of mRNA expression of the GH–IGF system in the rat proximal tibial growth plate quantitatively. Growth plates were microdissected into individual zones. RNA was extracted, reverse transcribed and analyzed by real-time PCR. In 1-week-old animals, IGF-I mRNA expression was minimal in growth plate compared with perichondrium, metaphyseal bone, muscle, and liver (70-, 130-, 215-, and 400-fold less). In contrast, IGF-II mRNA was expressed at higher levels than in bone and liver (65- and 2-fold). IGF-II expression was higher in the proliferative and resting zones compared with the hypertrophic zone (P < 0.001). GH receptor and type 1 and 2 IGF receptors were expressed throughout the growth plate. Expression of IGF-binding proteins (IGFBPs)-1 through -6 mRNA was low throughout the growth plate compared with perichondrium and bone. With increasing age (3-, 6-, 9-, and 12-week castrated rats), IGF-I mRNA levels increased in the proliferative zone (PZ) but remained at least tenfold lower than levels in perichondrium and bone. IGF-II mRNA decreased dramatically in PZ (780-fold; P < 0.001) whereas, type 2 IGF receptor and IGFBP-1, IGFBP-2, IGFBP-3, and IGFBP-4 increased significantly with age in growth plate and/or surrounding perichondrium and bone. These data suggest that IGF-I protein in the growth plate is not produced primarily by the chondrocytes themselves. Instead, it derives from surrounding perichondrium and bone. In addition, the decrease in growth velocity that occurs with age may be caused, in part, by decreasing expression of IGF-II and increasing expression of type 2 IGF receptor and multiple IGFBPs.


2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Seshagiri Rao Nandula ◽  
Nikhila Aimalla ◽  
Nabanita KUNDU ◽  
Sabyasachi Sen

Introduction: Diabetes and obesity are known to cause adipose inflammation, elevated oxidative stress by reactive oxygen species (ROS) accumulation. In this report we studied the effect of human adipose derived mesenchymal stroma cells (MSCs) overexpressing antioxidants both mitochondrial (Sod2) and cytosolic (Catalase) to reduce oxidative stress and systemic inflammation in DIO mouse model. Methods: C57BL/6J male mice (4–6 weeks old) were obtained from the Jackson Lab. Obesity, glucose intolerance, and insulin resistance were induced by feeding the mice a 60% fat high-fat diet (HFD) for 12 weeks. Mouse adipose-derived MSCs and adenovirus constructs containing GFP (Null, SOD2 and Catalase), were obtained. Liver and fat tissues gene expression, liver and fat depots H& E staining and liver triglycerides (L-TG) were quantified. Results: Triglyceride assay confirmed reduced liver fat accumulation in animals that received combination -MSCs. The gene expression analysis by qPCR for liver and omental fat shows upregulation of Ucp1, Pgc1a and Prdm16 genes with concomitant increase in all antioxidant (Sod2, Sod3 and Catalase) mRNA expression. Further the systemic TNF-α levels were decreased in the mice received MSC-Sod2+catalase. Glucose tolerance showed a improvement trend with low area under curve (AUC) values for mice that received MSCs with both Sod2 and catalase upregulated compared to control null group. Discussion: The combination effect of both mitochondrial and cytosolic anti-oxidants reduced systemic inflammation and liver triglyceride levels in diet induced obesity mouse model compared to SOD2, Catalase and Null MSCs. An increase mRNA expression of genes associated with browning of white adipose tissue deposits might have contributed to improvement in NAFLD along with systemic reduction in TNF-α. Genetically modified MSC therapy can be a promising option for treating obesity and diabetes.


1963 ◽  
Vol 44 (3) ◽  
pp. 475-480 ◽  
Author(s):  
R. Grinberg

ABSTRACT Radiologically thyroidectomized female Swiss mice were injected intraperitoneally with 131I-labeled thyroxine (T4*), and were studied at time intervals of 30 minutes and 4, 28, 48 and 72 hours after injection, 10 mice for each time interval. The organs of the central nervous system and the pituitary glands were chromatographed, and likewise serum from the same animal. The chromatographic studies revealed a compound with the same mobility as 131I-labeled triiodothyronine in the organs of the CNS and in the pituitary gland, but this compound was not present in the serum. In most of the chromatographic studies, the peaks for I, T4 and T3 coincided with those for the standards. In several instances, however, such an exact coincidence was lacking. A tentative explanation for the presence of T3* in the pituitary gland following the injection of T4* is a deiodinating system in the pituitary gland or else the capacity of the pituitary gland to concentrate T3* formed in other organs. The presence of T3* is apparently a characteristic of most of the CNS (brain, midbrain, medulla and spinal cord); but in the case of the optic nerve, the compound is not present under the conditions of this study.


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