scholarly journals Transgenic Mice Overexpressing Des-Acyl Ghrelin Show Small Phenotype

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 355-364 ◽  
Author(s):  
Hiroyuki Ariyasu ◽  
Kazuhiko Takaya ◽  
Hiroshi Iwakura ◽  
Hiroshi Hosoda ◽  
Takashi Akamizu ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Biological Effects ◽  
Lower Body ◽  
Acid Modification ◽  
Male And Female ◽  
Body Weights ◽  
Igf I ◽  
Actin Promoter ◽  
Acyl Ghrelin ◽  
Serum Gh

Ghrelin, a 28-amino acid acylated peptide, displays strong GH-releasing activity in concert with GHRH. The fatty acid modification of ghrelin is essential for the actions, and des-acyl ghrelin, which lacks the modification, has been assumed to be devoid of biological effects. Some recent reports, however, indicate that des-acyl ghrelin has effects on cell proliferation and survival. In the present study, we generated two lines of transgenic mice bearing the preproghrelin gene under the control of chicken β-actin promoter. Transgenic mice overexpressed des-acyl ghrelin in a wide variety of tissues, and plasma des-acyl ghrelin levels reached 10- and 44-fold of those in control mice. They exhibited lower body weights and shorter nose-to-anus lengths, compared with control mice. The serum GH levels tended to be lower, and the serum IGF-I levels were significantly lower in both male and female transgenic mice than control mice. The responses of GH to administered GHRH were normal, whereas those to administered ghrelin were reduced, especially in female transgenic mice, compared with control mice. These data suggest that overexpressed des-acyl ghrelin may modulate the GH-IGF-I axis and result in small phenotype in transgenic mice.

scholarly journals Effects of Antagonists of Growth Hormone-Releasing Hormone (GHRH) on GH and Insulin-Like Growth Factor I Levels in Transgenic Mice Overexpressing the Human GHRH Gene, an Animal Model of Acromegaly*

Endocrinology ◽  
1997 ◽  
Vol 138 (11) ◽  
pp. 4536-4542 ◽  
Author(s):  
Magdolna Kovacs ◽  
Rhonda D. Kineman ◽  
Andrew V. Schally ◽  
Marta Zarandi ◽  
Kate Groot ◽  
...  
Keyword(s):  
Animal Model ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Messenger Rna ◽  
Pituitary Cells ◽  
Releasing Hormone ◽  
Factor I ◽  
Igf I ◽  
Ghrh Antagonists ◽  
Serum Gh

Abstract Transgenic mice overexpressing the human GH-releasing hormone (hGHRH) gene, an animal model of acromegaly, were used to investigate the effects of potent GHRH antagonists MZ-4–71 and MZ-5–156 on the excessive GH and insulin-like growth factor I (IGF-I) secretion caused by overproduction of hGHRH. Because metallothionein (MT)-GHRH mice express the hGHRH transgene in various tissues, including the pituitary and hypothalamus, initial experiments focused on the effectiveness of the GHRH antagonists in blocking basal and stimulated GH secretion from pituitary cells in vitro. Both MZ-4–71 and MZ-5–156 suppressed basal release of GH from superfused MT-GHRH pituitary cells, apparently by blocking the action of endogenously produced hGHRH. In addition, these antagonists effectively eliminated the response to stimulatory action of exogenous hGHRH(1–29)NH2 (30 and 100 nm). To ascertain whether MZ-4–71 and MZ-5–156 could antagonize the effect of hGHRH hyperstimulation in vivo, each antagonist was administered to MT-GHRH transgenic mice in a single iv dose of 10–200 μg. Both compounds decreased serum GH levels in transgenic mice by 39–72% at 1 h after injection. The inhibitory effect of 50 μg MZ-5–156 was maintained for 5 h. Twice daily ip administration of 100 μg MZ-5–156 for 3 days suppressed the highly elevated serum GH and IGF-I concentrations in transgenic mice by 56.8% and 39.0%, respectively. This treatment also reduced IGF-I messenger RNA levels in the liver by 21.8% but did not affect the level of GH messenger RNA in the pituitary. Our results demonstrate that GHRH antagonists MZ-4–71 and MZ-5–156 can inhibit elevated GH levels caused by overproduction of hGHRH. The suppression of circulating GH concentrations induced by the antagonists seems to be physiologically relevant, because both IGF-I secretion and synthesis also were reduced. Our findings, showing the suppression of GH and IGF-I secretion with GHRH antagonists, suggest that this class of analogs could be used for the diagnosis and therapy of disorders characterized by excessive GHRH secretion.

scholarly journals Relative growth of the skull and postcranium in giant transgenic mice

1990 ◽  
Vol 56 (1) ◽  
pp. 21-34 ◽  
Author(s):  
Brian T. Shea ◽  
Robert E. Hammer ◽  
Ralph L. Brinster ◽  
Matthew R. Ravosa
Keyword(s):  
Transgenic Mice ◽  
Growth Patterns ◽  
Cross Sectional ◽  
Relative Growth ◽  
Normal Littermate ◽  
Skeletal Size ◽  
Body Weights ◽  
Igf I ◽  
Growth Controls ◽  
Normal Controls

SummaryCross-sectional allometric growth patterns of the cranial and postcranial skeleton were compared between giant transgenic (MT-rGH) mice and their normal littermate controls. Body weights, external body dimensions, and a series of cranial and postcranial linear dimensions of the skeleton were determined for samples of known age. Comparative bivariate and multivariate allometric analyses were completed in order to determine whether (1) the larger transgenic mice differed significantly from the normal controls in aspects of body and skeletal proportions, and (2) any such proportion differences resulted from general allometric effects of overall weight or skeletal size increase. Results demonstrate that the transgenic mice do exhibit significantly different body and skeletal proportions than normal control adults. Allometric comparisons of the skeletal dimensions relative to body weight reveal similar coefficients of growth allometry but several differences in y-intercept values in the transgenic vs. control groups. The comparisons among the skeletal dimensions of the skull and postcranium generally reveal the sharing and differential extension of common growth allometries in the two groups. Thus, the elevated levels of growth hormone (GH) and insulin-like growth factor I (IGF-I) in the transgenic mice appear to result in increased overall growth for the various skeletal elements, but in the relative proportions determined by intrinsic growth controls within that system.

scholarly journals Chronic Dexamethasone Treatment Leads to Less Weight Gain and Ameliorated Glucose Tolerance in Mice; Role of the Cytoprotective Nrf2 Pathway

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A806-A807
Author(s):  
Fotini Filippopoulou ◽  
Eleni Douni ◽  
Antonia Sophocleus ◽  
Ioannis Habeos ◽  
Dionysios Chartoumpekis
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Micro Ct ◽  
Lower Body ◽  
Male Mice ◽  
Dexamethasone Treatment ◽  
Male And Female ◽  
Bone Parameters ◽  
Glucose Levels ◽  
Body Weights

Abstract Introduction: Chronic glucocorticoid administration is necessary in a variety of conditions including but not limited to autoimmune, inflammatory and cancer-related diseases in order to relieve symptoms and sustain disease progression. However, there are adverse effects that include increase in glucose levels and others whose severity depends on the dose and duration of glucocorticoid exposure. It has been described that dexamethasone induces oxidative stress in cells by increasing reactive oxygen species (ROS) and this is one of the causes of insulin resistance at the cellular level. Nrf2 is a transcription factor which co-ordinates the antioxidant response and its activation has been shown to ameliorate insulin resistance in murine models. Hypothesis: We hypothesized that deletion of Nrf2 will lead to a more glucose intolerant insulin resistant phenotype in mice chronically treated with dexamethasone as cells would be exposed to higher ROS levels. Methods: To this end, 3-months old wild-type (WT) and Nrf2 knockout (KO) C57BL6J mice were treated intraperitoneally with 2 mg/kg dexamethasone or saline 3 times per week for 3 months. 5-10 mice were included per genotype per treatment and both male and female mice were used. Weekly measurements of body weights were performed and intraperitoneal glucose tolerance tests were done on the second and third month of treatment. Mice were sacrificed 24 hours after the last dose of dexamethasone and blood, white adipose tissue, soleus muscle and liver were collected for RNA preparation and quantitative RT-PCR analysis. Quantitative analysis of trabecular bone parameters was performed by micro-CT. Results: Both male and female mice treated with dexamethasone gained less weight over time and surprisingly were more glucose tolerant than the control group. Absence of Nrf2 did not seem to considerably affect the body weight but KO mice tended to have lower body weights after dexamethasone treatment in both genders with the effect on male mice being statistically significant (25% lower, p<0.05). Surprisingly, both WT and KO mice of both genders showed lower fasting blood glucose levels after 3 months of treatment and better glucose tolerance. Livers of KO mice showed lower levels (~50%) of the cytoprotective genes Nqo1 and Gclc as expected but no difference was observed after dexamethasone treatment. Sarcopenia muscle markers Mafbx1 and Murf1 showed no significant changes. Male mice showed increased expression of Pnpla3 in white adipose tissue indicating increased lipolysis upon dexamethasone exposure. Micro-CT showed minor changes in the bone parameters without difference between male WT and Nrf2KO mice. Conclusions: Dexamethasone unexpectedly led to better glucose tolerance and lower body weight which is uncommon in humans but it has been described previously in mouse models. More analyses are in progress to fully elucidate this phenotype.

scholarly journals Preconceptional smoking alters spermatozoal miRNAs of murine fathers and affects offspring’s body weight

2021 ◽  
Author(s):  
Barbara Hammer ◽  
Latha Kadalayil ◽  
Eistine Boateng ◽  
Dominik Buschmann ◽  
Faisal I. Rezwan ◽  
...  
Keyword(s):  
Body Weight ◽  
Early Life ◽  
The Body ◽  
Epigenetic Changes ◽  
Lower Body ◽  
Male And Female ◽  
Body Weights ◽  
F1 Progeny ◽  
Paternal Smoking ◽  
Mainstream Cigarette Smoke

Abstract Background Active smoking has been reported among 7% of teenagers worldwide, with ages ranging from 13 to 15 years. An epidemiological study suggested that preconceptional paternal smoking is associated with adolescent obesity in boys. We developed a murine adolescent smoking model before conception to investigate the paternal molecular causes of changes in offspring’s phenotype. Method Male and female C57BL/6J mice were exposed to increasing doses of mainstream cigarette smoke (CS) from onset of puberty for 6 weeks and mated with room air (RA) controls. Results Thirteen miRNAs were upregulated and 32 downregulated in the spermatozoa of CS-exposed fathers, while there were no significant differences in the count and morphological integrity of spermatozoa, as well as the proliferation of spermatogonia between CS- and RA-exposed fathers. Offspring from preconceptional CS-exposed mothers had lower body weights (p = 0.007). Moreover, data from offspring from CS-exposed fathers suggested a potential increase in body weight (p = 0.062). Conclusion We showed that preconceptional paternal CS exposure regulates spermatozoal miRNAs, and possibly influences the body weight of F1 progeny in early life. The regulated miRNAs may modulate transmittable epigenetic changes to offspring, thus influence the development of respiratory- and metabolic-related diseases such as obesity, a mechanism that warrants further studies for elaborate explanations.

Gender Differences in Clothing Worn in Current Popular Comic Books

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Kyle Landon Jossy
Keyword(s):  
Gender Differences ◽  
Content Analysis ◽  
Comic Books ◽  
Book Industry ◽  
Comic Book ◽  
Lower Body ◽  
Female Characters ◽  
Male And Female ◽  
Males And Females

This study looked at how males and females were portrayed, based on the amount of skin shown in the clothing worn.  A Content analysis was performed on a sample of 20 randomly selected popular comics from the last 3 years.  Both male and female characters were rated on how much skin they showed in three clothing categories; neck line, sleeve length, and lower body.  Results showed that in all 3 categories, women consistently wore more revealing clothing.  The findings demonstraetd that the comic book industry is comparable to other forms of media, in the sexualization of female characters, by having them wear more revealing clothing.

Increased neural activity in transgenic mice with brain IGF-I overexpression

Neuroreport ◽  
1997 ◽  
Vol 8 (13) ◽  
pp. 2907-2911 ◽  
Author(s):  
Gabriel Gutiérrez-Ospina ◽  
Leilani Saum ◽  
Ali Suha Calikoglu ◽  
Sofía Díaz-Cintra ◽  
Fernando A. Barrios ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Neural Activity ◽  
Igf I

Interactions of insulin-like growth factor (IGF)-II and growth hormone in vivo: circulating levels of IGF-I and IGF-binding proteins in transgenic mice

1997 ◽  
pp. 701-708 ◽  
Author(s):  
A Blackburn ◽  
RA Dressendorfer ◽  
WF Blum ◽  
M Erhard ◽  
G Brem ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Transgene Expression ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Standard Diet ◽  
Igf I ◽  
Igf Binding ◽  
B Mice

To study interactions between insulin-like growth factor-II (IGF-II) and growth hormone (GH) in vivo, we crossed hemizygous transgenic mice carrying phosphoenolpyruvate carboxykinase (PEPCK)-IGF-II fusion genes with hemizygous PEPCK-bovine GH (bGH) transgenic mice. Offspring harbouring both transgenes (IB), the IGF-II transgene (I) or the bGH transgene (B), and non-transgenic littermates (C) were obtained. Blood samples were taken before (end of week 12) and after (end of week 14) the mice had received a diet high in protein and low in carbohydrates to stimulate PEPCK promoter-controlled transgene expression. Mean serum GH concentrations of both B and IB mice corresponded to 900 ng/ml and increased more than twofold (P < 0.001) after 1 week of the high-protein diet. GH concentrations in controls and I mice were less than 20 ng/ml. Serum IGF-II concentrations in I and IB mice were three-to fourfold higher than those in C and B mice. Whereas IGF-II concentrations were not changed by the high-protein diet in the last two groups, serum IGF-II increased significantly in I (P < 0.001) and IB mice (P < 0.05). This increase was significantly (P < 0.05) less pronounced in IB than in C and I mice. Circulating IGF-I concentrations were about twofold (P < 0.001) higher in B and IB than in C and I mice, and showed a tendency to be lower in I than in C and in IB than in B mice when animals were maintained on the standard diet. The high-protein diet did not change circulating IGF-I concentrations in controls and B mice, but resulted in a significant reduction of serum IGF-I concentrations in I (P < 0.05) and IB mice (P < 0.001). Consequently, after PEPCK-IGF-II transgene expression was stimulated, serum IGF-I concentrations were significantly (P < 0.05) lower in I than in C and in IB than in B mice. Serum IGF-binding protein (IGFBP)-2 concentrations were significantly (P < 0.05) higher in I mice than in all other groups when mice were maintained on the standard diet, with a tendency to reduced IGFBP-2 concentrations in B mice. After the high-protein diet, serum IGFBP-2 concentrations did not change in C and I mice, but increased by two- to threefold in B and IB mice (P < 0.001). Serum IGFBP-3 concentrations tended to be greater in B and IB than in C and I mice, but these differences were mostly not significant. IGFBP-4 concentrations were significantly (P < 0.001) increased by GH overproduction in B and IB mice. Our data suggest that the reduction in circulating IGF-I concentrations by increased IGF-II is most probably due to the limited serum IGF binding capacity and the short half-life of free IGFs, rather than to a reduction in GH-dependent IGF-I production. Effects of GH overproduction on serum IGFBP-2 concentrations depend on dietary factors and may be both inhibitory and stimulatory.

PRE-MATERNAL ISOLATION EFFECTS ON BEHAVIOUR AND ENDOCRINE FUNCTION OF OFFSPRING

1969 ◽  
Vol 62 (2) ◽  
pp. 367-384 ◽  
Author(s):  
A. M. Sackler ◽  
A. S. Weltman ◽  
R. Schwartz ◽  
P. Steinglass
Keyword(s):  
Locomotor Activity ◽  
Growth Rates ◽  
Female Offspring ◽  
The Body ◽  
Endocrine Function ◽  
Male And Female ◽  
Isolation Stress ◽  
Developmental Growth ◽  
Body Weights ◽  
And Control

ABSTRACT This report was designed to determine combined effects of maternal endocrine imbalances and abnormal behaviour due to prolonged isolation stress of female mice on the behaviour, developmental growth rate and endocrine function of their offspring. Sixty female albino mice averaging 19 g were divided equally into isolated and control groups. The isolated females were housed singly; control females were maintained in groups of 2 mice per cage. After observation of behavioural and physiological effects characteristic of isolation stress in the test mice, all isolated and control mice were mated after a 6½ month experimental, isolation period. No differences were observed in fertility and fecundity of the two groups of mothers. Analyses of developmental growth rates of the litters of the isolated versus control mothers showed significantly lower body weights in the test offspring at 3 and 4 weeks of age. The body weights of the female offspring remained significantly lower from the 4th to 11th weeks. The effects on the body weights of the male offspring declined and were no longer statistically significant at the 5th to 11 weeks. Locomotor activity at 4½ and 8 weeks of age was markedly or significantly higher in the male and female mice from isolated mothers. Tail-blood samples taken prior to autopsy at 5 and 11 weeks of age revealed significant decreases in the total leukocyte and eosinophil counts of both sexes. At the two ages, the absolute and relative spleen and thymus weights of the male and female offspring were markedly and/or significantly lower than the values observed in counterpart young from control females. Significant decreases were also observed in the absolute gonadal organ weights of both sexes at 11 weeks of age. The various data indicated inhibited growth rates, heightened locomotor activity and evasiveness, as well as evidence of increased adrenocortical function in the offspring from test mothers. The gonadal weight decreases suggested retarded gonadal development. Further studies using split-litter techniques are required to differentiate the effects of prenatal endocrine imbalances versus postnatal maternal influence (i. e., nursing care) on the offspring.

Effects of refeeding of undernourished and insulin treatment of diabetic neonatal rats on IGF and IGFBP

1996 ◽  
Vol 271 (2) ◽  
pp. E223-E231 ◽  
Author(s):  
L. Goya ◽  
F. Rivero ◽  
M. A. Martin ◽  
R. Arahuetes ◽  
E. R. Hernandez ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Growth Factor ◽  
Mrna Expression ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
Insulin Like Growth Factor ◽  
Neonatal Rats ◽  
Igf I ◽  
Serum Gh

The effect of refeeding and insulin treatment of undernourished and diabetic neonatal rats, respectively, on the regulation of insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) was investigated. The changes in body weight, insulinemia, glycemia, serum IGF-I, and growth hormone (GH) as well as the increase of the 30-kDa IGFBP in undernourished and diabetic neonatal rats previously shown elsewhere were reversed by refeeding and insulin treatment, respectively. Also, changes in liver mRNA expression of IGF-I and-II and IGFBP-1 and -2 were restored in refed undernourished and IGF-I and IGFBP-1 levels recovered in insulin-treated diabetic rats. However, serum GH was still below normal after rehabilitation in both situations. Thus the present results support the idea of a GH-independent IGF/ IGFBP regulation mediated by a balance of insulin and nutrients as has already been suggested in previous neonatal studies.

Oral vanadyl sulfate in treatment of diabetes mellitus in rats

1989 ◽  
Vol 257 (3) ◽  
pp. H904-H911 ◽  
Author(s):  
S. Ramanadham ◽  
J. J. Mongold ◽  
R. W. Brownsey ◽  
G. H. Cros ◽  
J. H. McNeill
Keyword(s):  
Heart Function ◽  
Plasma Concentrations ◽  
Vanadyl Sulfate ◽  
Lower Body ◽  
Endogenous Insulin ◽  
Body Weights ◽  
Treatment Of Diabetes ◽  
Working Heart ◽  
Circulating Levels ◽  
Insulin Like Activity

Recent reports have suggested that vanadium in the form of vanadyl (+IV) possesses insulin-like activity. Therefore, in the present study we examined the effects of administering oral vanadyl to diabetic animals. Wistar rats made diabetic with streptozotocin and age-matched controls were maintained for 10 wk in the absence and presence of vanadyl sulfate trihydrate in the drinking water. In the presence of vanadyl, decreases in rate of growth and circulating levels of insulin were the only significant alterations recorded in control animals. In contrast, diabetic animals treated with vanadyl, despite having lower body weights and insulin levels, had normal plasma concentrations of glucose, lipid, creatinine, and thyroid hormone. In addition, abnormalities in isolated working heart function and glycerol output from adipose tissue of diabetic animals were also corrected after vanadyl treatment. These results suggest that vanadium when used in the vanadyl form is effective in diminishing the diabetic state in the rat by substituting for and replacing insulin or possibly by enhancing the effects of endogenous insulin.

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