scholarly journals Gonad-related factors promote muscle performance gain during postnatal development in male and female mice

2017 ◽  
Vol 313 (1) ◽  
pp. E12-E25 ◽  
Author(s):  
Vanessa Ueberschlag-Pitiot ◽  
Amalia Stantzou ◽  
Julien Messéant ◽  
Megane Lemaitre ◽  
Daniel J. Owens ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Postnatal Development ◽  
Muscle Fiber ◽  
Muscle Performance ◽  
Performance Gain ◽  
Related Factors ◽  
Muscle Weight ◽  
Male And Female ◽  
Female Mice ◽  
Muscle Contractile

To better define the role of male and female gonad-related factors (MGRF, presumably testosterone, and FGRF, presumably estradiol, respectively) on mouse hindlimb skeletal muscle contractile performance/function gain during postnatal development, we analyzed the effect of castration initiated before puberty in male and female mice. We found that muscle absolute and specific (normalized to muscle weight) maximal forces were decreased in 6-mo-old male and female castrated mice compared with age- and sex-matched intact mice, without alteration in neuromuscular transmission. Moreover, castration decreased absolute and specific maximal powers, another important aspect of muscle performance, in 6-mo-old males, but not in females. Absolute maximal force was similarly reduced by castration in 3-mo-old muscle fiber androgen receptor (AR)-deficient and wild-type male mice, indicating that the effect of MGRF was muscle fiber AR independent. Castration reduced the muscle weight gain in 3-mo mice of both sexes and in 6-mo females but not in males. We also found that bone morphogenetic protein signaling through Smad1/5/9 was not altered by castration in atrophic muscle of 3-mo-old mice of both sexes. Moreover, castration decreased the sexual dimorphism regarding muscle performance. Together, these results demonstrated that in the long term, MGRF and FGRF promote muscle performance gain in mice during postnatal development, independently of muscle growth in males, largely via improving muscle contractile quality (force and power normalized), and that MGFR and FGRF also contribute to sexual dimorphism. However, the mechanisms underlying MGFR and FGRF actions remain to be determined.

Fiber number, area, and composition of mouse soleus muscle following enlargement

1985 ◽  
Vol 58 (2) ◽  
pp. 619-624 ◽  
Author(s):  
B. F. Timson ◽  
B. K. Bowlin ◽  
G. A. Dudenhoeffer ◽  
J. B. George
Keyword(s):  
Muscle Fiber ◽  
Soleus Muscle ◽  
Histological Section ◽  
Type I ◽  
Muscle Weight ◽  
Cross Sectional ◽  
Male And Female ◽  
Female Mice ◽  
Fiber Area ◽  
Fiber Number

Muscle fiber number, cross-sectional area, and composition were studied in response to enlargement produced by synergistic ablation in the mouse soleus muscle. The effect of the location of a histological section on the number of fibers that appear in the section was also studied using the mouse soleus muscle. Enlargement was produced in the soleus muscle of 15 male and 15 female mice by ablation of the ipsilateral gastrocnemius muscle. Fiber counts, using the nitric acid digestion method, revealed no difference between control and enlarged muscles in male and female mice. Mean fiber area, determined by planimetry, was 49.1 and 34.5% greater following enlargement in male and female mice, respectively. Increase in muscle weight could be totally accounted for by the increase in fiber area following enlargement. A transformation of type II to type I fibers occurred following enlargement for both sexes. Counts of fibers from histological sections revealed that there was a progressive decrease in the fiber number as the section was moved from the belly to the distal end of the muscle. The results of these studies indicate that muscle enlargement in the mouse soleus muscle is due to hypertrophy of the existing muscle fibers.

The melanocortin-3 receptor is a pharmacological target for the regulation of anorexia

2021 ◽  
Vol 13 (590) ◽  
pp. eabd6434
Author(s):  
Patrick Sweeney ◽  
Michelle N. Bedenbaugh ◽  
Jose Maldonado ◽  
Pauline Pan ◽  
Katelyn Fowler ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Feeding Behavior ◽  
Critical Role ◽  
Brain Regions ◽  
Sexually Dimorphic ◽  
Male And Female ◽  
Female Mice ◽  
Bidirectional Regulation ◽  
Fear And Anxiety ◽  
Agouti Related Protein

Ablation of hypothalamic AgRP (Agouti-related protein) neurons is known to lead to fatal anorexia, whereas their activation stimulates voracious feeding and suppresses other motivational states including fear and anxiety. Despite the critical role of AgRP neurons in bidirectionally controlling feeding, there are currently no therapeutics available specifically targeting this circuitry. The melanocortin-3 receptor (MC3R) is expressed in multiple brain regions and exhibits sexual dimorphism of expression in some of those regions in both mice and humans. MC3R deletion produced multiple forms of sexually dimorphic anorexia that resembled aspects of human anorexia nervosa. However, there was no sexual dimorphism in the expression of MC3R in AgRP neurons, 97% of which expressed MC3R. Chemogenetic manipulation of arcuate MC3R neurons and pharmacologic manipulation of MC3R each exerted potent bidirectional regulation over feeding behavior in male and female mice, whereas global ablation of MC3R-expressing cells produced fatal anorexia. Pharmacological effects of MC3R compounds on feeding were dependent on intact AgRP circuitry in the mice. Thus, the dominant effect of MC3R appears to be the regulation of the AgRP circuitry in both male and female mice, with sexually dimorphic sites playing specialized and subordinate roles in feeding behavior. Therefore, MC3R is a potential therapeutic target for disorders characterized by anorexia, as well as a potential target for weight loss therapeutics.

scholarly journals Rapid Changes in Anterior Pituitary Cell Phenotypes in Male and Female Mice after Acute Cold Stress

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2159-2167 ◽  
Author(s):  
Laura Senovilla ◽  
Lucía Núñez ◽  
Carlos Villalobos ◽  
Javier García-Sancho
Keyword(s):  
Sexual Dimorphism ◽  
Cold Stress ◽  
Relative Abundance ◽  
Anterior Pituitary ◽  
Cell Types ◽  
Male And Female ◽  
Female Mice ◽  
Rapid Changes ◽  
Cell Phenotypes ◽  
Different Cell Types

The anterior pituitary (AP) is made of five different cell types. The relative abundance and phenotype of AP cells may change in different physiological situations as an expression of pituitary plasticity. Here, we analyze in detail the phenotype of mouse corticotropes and the effects of acute cold stress on AP cell populations. The hormone content and the expression of hypothalamic-releasing hormone (HRH) receptors in all the five AP cell types were studied in the male and female mice at rest and after a 30-min cold stress. Expression of HRH receptors was evidenced by imaging the single-cell cytosolic Ca2+ responses in fura-2-loaded cells. Hormone contents were studied by multiple, simultaneous immunofluorescence of all the five hormones. Corticotropes displayed a striking sexual dimorphism, even in the resting condition. Male corticotropes showed the orthodox phenotype. They were monohormonal, storing only ACTH, and monoreceptorial, responding only to CRH. In contrast, female corticotropes were made of about equal parts of orthodox cells and multifunctional cells, which co-stored additional AP hormones and expressed additional HRH receptors. Cold stress did not modify the number of ACTH containing cells, but, according to immunostaining, it increased the relative abundance of other AP cell types at the expense of the pool of cells storing no hormones. Cold stress also modified the response to CRH and other HRHs. Most of these phenotypical changes presented a strong sexual dimorphism. These results indicate that pituitary plasticity is even larger than previously thought.

scholarly journals Sexual Dimorphism in Doxorubicin-induced Systemic Inflammation: Implications for Hepatic Cytochrome P450 Regulation

2020 ◽  
Vol 21 (4) ◽  
pp. 1279
Author(s):  
Marianne K.O. Grant ◽  
Ibrahim Y. Abdelgawad ◽  
Christine A. Lewis ◽  
Beshay N. Zordoky
Keyword(s):  
Sex Differences ◽  
Cytochrome P450 ◽  
Sexual Dimorphism ◽  
Inflammatory Response ◽  
Systemic Inflammation ◽  
Dependent Manner ◽  
Male And Female ◽  
Female Mice ◽  
Organ Toxicity ◽  
Hepatic Cytochrome

Doxorubicin (DOX) is an effective chemotherapeutic agent used to treat a wide variety of malignancies. In addition to its multi-organ toxicity, DOX treatment has been shown to induce systemic inflammation in patients and experimental animals. Inflammation alters the expression of hepatic cytochrome P450 (CYP) enzymes, which play important roles in drug metabolism and DOX-induced toxicity. Significant sex differences have been reported in DOX-induced toxicity; however, sex differences in DOX-induced systemic inflammation and the potential effects on hepatic CYP expression have not been determined. In the current work, male and female C57Bl/6 mice were administered DOX (20 mg/kg by intraperitoneal injection), and groups of mice were sacrificed 24 and 72 h after DOX administration. DOX elicited a systemic inflammatory response in both male and female mice, but the inflammatory response was stronger in male mice. DOX altered the expression of hepatic CYP isoforms in a sex-dependent manner. Most notably, inhibition of Cyp2c29 and Cyp2e1 was stronger in male than in female mice, which paralleled the sex differences in systemic inflammation. Therefore, sex differences in DOX-induced systemic inflammation may lead to sexually dimorphic drug interactions, in addition to contributing to the previously reported sexual dimorphism in specific DOX-induced organ toxicity.

scholarly journals Combined Effects of Exercise and Phytoanabolic Extracts in Castrated Male and Female Mice

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1177
Author(s):  
Jerônimo P. Martins ◽  
Lucia C. Silva ◽  
Matheus S. Nunes ◽  
Gabriel Rübensam ◽  
Jarbas R. Oliveira ◽  
...  
Keyword(s):  
Resistance Exercise ◽  
Hdl Cholesterol ◽  
Scientific Data ◽  
Herbal Extracts ◽  
Muscle Weight ◽  
Male And Female ◽  
Female Mice ◽  
Eurycoma Longifolia ◽  
Ajuga Turkestanica ◽  
General Physical

Dry extracts from the Eurasian plants, Ajuga turkestanica, Eurycoma longifolia, and Urtica dioica have been used as anabolic supplements, despite the limited scientific data on these effects. To assess their actions on early sarcopenia signs, male and female castrated mice were supplemented with lyophilized extracts of the three plants, isolated or in association (named TLU), and submitted to resistance exercise. Ovariectomy (OVX) led to body weight increase and non-high-density cholesterol (HDL) cholesterol elevation, which had been restored by exercise plus U. dioica extract, or by exercise and TLU, respectively. Orchiectomy (ORX) caused skeletal muscle weight loss, accompanied by increased adiposity, being the latter parameter reduced by exercise plus E. longifolia or U. dioica extracts. General physical activity was improved by exercise plus herbal extracts in either OVX or ORX animals. Exercise combined with TLU improved resistance to fatigue in OVX animals, though A. turkestanica enhanced the grip strength in ORX mice. E. longifolia or TLU also reduced the ladder climbing time in ORX mice. Resistance exercise plus herbal extracts partly altered gastrocnemius fiber size frequencies in OVX or ORX mice. We provide novel data that tested ergogenic extracts, when combined with resistance exercise, improved early sarcopenia alterations in castrated male and female mice.

scholarly journals SUN-LB93 Mineralocorticoid Receptor Mediates Sex-Dependent Anticontractile Effect of Perivascular Adipose Tissue in Obese Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jamaira A Victorio ◽  
Israelle Netto Freitas ◽  
Daniele Mendes Guizoni ◽  
Ana Paula Davel
Keyword(s):  
Sex Differences ◽  
Adipose Tissue ◽  
Sexual Dimorphism ◽  
Protein Expression ◽  
Vascular Function ◽  
Mineralocorticoid Receptor ◽  
Obese Mice ◽  
Perivascular Adipose Tissue ◽  
Male And Female ◽  
Female Mice

Abstract Obesity, a condition of excessive fat mass and subclinical inflammation, reached epidemic proportions with higher prevalence in women compared to men worldwide. Expansion of the perivascular adipose tissue (PVAT) is observed in obesity and clinical studies indicate a positive correlation between PVAT amount and body mass index. PVAT, a fat depot surrounding most of the vessels, modulates vascular function by releasing PVAT-derived factors such as adipokines that exert anticontractile effect in health individuals. Despite sexual dimorphism on PVAT morphology, it is still unknown whether or not there is sex differences in the PVAT modulating vascular function in the setting of obesity. Aldosterone-mineralocorticoid receptor (MR) signaling pathway has been demonstrated to be adipogenic and proinflammatory in classical fat depots and treatment with MR antagonists (A) might reverse vascular dysfunction and remodeling in obese models, especially in female sex. Therefore, we aimed to evaluate the anticontractile effect of PVAT in male and female obese mice and hypothesized that MR signaling would be involved in possible sex differences in PVAT dysfunction in obesity. Male and female C57Bl6/J mice were fed a chow or a high-fat diet (HFD, 60% energy from fat) for 20 weeks. At the last 4 weeks of HFD, female and male mice were treated with the MRA spironolactone (Spi, 100 mg/kg/day). HFD feeding significantly increased body weight and visceral adipose tissue, which was not modified by Spi treatment in both sexes. Resistance mesenteric arteries were isolated with or without PVAT and mounted in a wire myograph to evaluate vascular contractile responses. Lean male and female mice PVAT had an anticontractile effect in the response to phenylephrine that was greater in females than males. The anticontractile effect of PVAT was significantly impaired in obese females but not modified in males. HFD-induced dysfunctional PVAT was prevented by Spi treatment in females. Next, we evaluated the protein expression of aldosterone-synthase CYP11B2, serum and glucocorticoid-regulated kinase 1 (SGK1), and epithelial sodium channel subunits (ENaCs) in isolated mesenteric PVAT of lean and obese male and female mice. There was an increased expression of CYP11B2, SGK1 and ENaCs only in obese female PVAT. Protein expression of adiponectin, a major PVAT-released adipokine was also increased in female mesenteric PVAT. In conclusion, the findings suggest sexual dimorphism in PVAT function in health and in obesity. Although anticontractile role of PVAT was exacerbated in lean female mice, female sex was more susceptible to develop PVAT dysfunction in the setting of obesity which was prevented by MR blockade. HFD-induced PVAT dysfunction in females was associated with increased expression of SGK1 and ENaCs. Therefore, data suggest MR activation as a mechanism mediating sex differences in PVAT dysfunction. FAPESP, CAPES.

scholarly journals Phenotypic Sexual Dimorphism in Response to Dietary Fat Manipulation in C57BL/6J Mice

2020 ◽  
Author(s):  
Isabel Casimiro ◽  
Natalie D. Stull ◽  
Sarah A. Tersey ◽  
Raghavendra Mirmira
Keyword(s):  
Sexual Dimorphism ◽  
Locomotor Activity ◽  
Glucose Tolerance ◽  
Food Consumption ◽  
High Fat Diet ◽  
Male Mice ◽  
High Fat ◽  
Β Cell ◽  
Male And Female ◽  
Female Mice

Abstract Background:Obesity and the metabolic syndrome are increasingly prevalent in society and their complications and response to treatment exhibit sexual dimorphism. Mouse models of high fat diet-induced obesity are commonly used for both mechanistic and therapeutic studies of metabolic disease and diabetes. However, the inclusion of female mammals in obesity research has not been a common practice, and has resulted in a paucity of data regarding the effect of sex on metabolic parameters and its applicability to humans. Methods:Here we analyzed male and female C57BL/6J mice beginning at 4 weeks of age that were placed on a low-fat diet (LFD, 10% calories from fat), a Western Diet (WD, 45% calories from fat), or a high fat diet (HFD, 60% calories from fat). Assessments of body composition, glucose homeostasis, insulin production, and energy metabolism, as well as histological analyses of pancreata were performed. Results:Both male and female C57BL/6J mice had similar increases in total percent body weight gain with both WD and HFD compared to LFD, however, male mice gained weight earlier upon HFD or WD feeding compared to female mice. Male mice exhibited a decrease in both food consumption and activity with either WD or HFD compared to LFD, whereas female mice did not exhibit any differences in food intake and minimal changes in locomotor activity on any diet. Glucose tolerance tests performed at 4, 12 and 20 weeks of dietary intervention revealed impaired glucose tolerance that was worse in male mice compared to females. Furthermore, male mice exhibited an increase in pancreatic β cell area as well as reduced insulin sensitivity after HFD feeding compared to WD or LFD, whereas female mice did not. Conclusions:Male and female C57BL/6J mice exhibited strikingly different responses in weight, food consumption, locomotor activity, and β cell adaptation upon dietary manipulation, with the latter exhibiting less striking phenotypic changes. We conclude that the nature of these responses emphasizes the need to contextualize studies of obesity pathophysiology and treatment with respect to sex.

Rapid Development of Vasopressin Resistance in Dietary Potassium Deficiency

2021 ◽  
Author(s):  
Lama Al-Qusairi ◽  
P Richard Grimm ◽  
Ava Marie Zapf ◽  
Paul A Welling
Keyword(s):  
Sexual Dimorphism ◽  
Water Balance ◽  
Rapid Development ◽  
Control Diet ◽  
Surrogate Marker ◽  
Plasma Potassium ◽  
Male And Female ◽  
Female Mice ◽  
Dietary Potassium ◽  
Apical Localization

The association between diabetes insipidus (DI) and chronic dietary potassium deprivation is well known but it remains uncertain how the disorder develops and whether it is influenced by the sexual dimorphism in potassium handling. Here, we determine the plasma potassium (PK) threshold for DI in male and female mice and ascertain if the DI is initiated by polydipsia, or a central or nephrogenic defect. C57BL6J mice were randomized to a control diet or to graded reductions in dietary K+ for 8 days, and kidney function and transporters involved in water balance were characterized. We found male and female mice develop polyuria and secondary polydipsia. Altered water balance coincides with a decrease in AQP2 phosphorylation and apical localization despite increased levels of the vasopressin surrogate marker, copeptin. No change in the protein abundance of the urea transporter, UT-A1, was observed. NKCC2 decreased only in males. DDAVP treatment failed to reverse water diuresis in K+-restricted mice. These findings indicate that even small fall in PK is associated with nephrogenic DI (NDI), coincident with the development of altered AQP2 regulation, implicating low PK as a causal trigger of NDI. We found PK decreased more in females, and consequently females were more prone to develop NDI. Together these data indicate that AQP2 regulation is disrupted by a small decrease in PK and the response is influenced by sexual dimorphism in potassium handling. These findings provide new insights into the mechanisms linking water and potassium balances, and support defining the disorder as "Potassium-Dependent NDI."

scholarly journals Late-Onset Pharmacological or Dietary Interventions Improve Healthspan and Lifespan in Male and Female Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 125-125
Author(s):  
Sarah Mitchell ◽  
Michael MacArthur ◽  
Alice Kane ◽  
Margaret Torrence ◽  
Huseyin Mehmet ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Late Onset ◽  
Frailty Index ◽  
Pharmacological Intervention ◽  
Blood Collection ◽  
Dietary Interventions ◽  
Male And Female ◽  
Female Mice ◽  
Age Related ◽  
Extended Lifespan

Abstract While late-onset dietary or pharmacological interventions can extend longevity in rodents, whether or not they can be used to reverse or forestall onset of aging-related symptoms (i.e. frailty) remains untested. Here, we employed three interventions to test this hypothesis. Male and female C57BL/6 mice were randomized to one of four groups: control, 15% calorie restriction (15CR), 0.1% Methionine Restriction (MR)or ZGN1062 (1.5mg/kg, drug in feed) starting at 21mo. Healthspan measurements (mouse clinical frailty index (FI), blood collection, and hematology) were performed every three months, and survival was assessed for all mice. At baseline there were no significant differences in frailty index. After 6mo FI increased consistent with reduced healthspan in control males (0.23□0.01 to 0.34□0.01 A.U, p<0.0001) and females at this age (0.19□0.03 to 0.24□0.01, p<0.0001). Male 15CR, MR and ZGN1062 mice had significantly lower FI scores at 27mo age (15CR: 0.32□0.01, p=0.02; MR: 0.31□0.01, p=0.0009; ZGN1062: 0.30□0.01, p<0.0001). Female mice were less frail than males at 27mo, suggesting sexual dimorphism in the timing of frailty onset in mice. ZGN1062 significantly extended lifespan in males (HR=0.56, p=0.007) and females (HR=0.46, p=0.001). There was a sexual dimorphism in the ability of 15CR and MR to extend lifespan, and a trend towards increased lifespan in males (HR=0.69, p=0.057 and HR=0.71, p=0.09) but not in females. Histological analysis for cause-of-death is ongoing. Taken together these data suggest that a pharmacological intervention associated with weight loss, which may be a more practical therapeutic strategy towards mitigation of age-related healthspan decline than dietary restriction-based interventions.

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