scholarly journals Opposite Effects of Androgens and Estrogens on Adipogenesis in Rat Preadipocytes: Evidence for Sex and Site-Related Specificities and Possible Involvement of Insulin-Like Growth Factor 1 Receptor and Peroxisome Proliferator-Activated Receptorγ 21

Endocrinology ◽  
2000 ◽  
Vol 141 (2) ◽  
pp. 649-656 ◽  
Author(s):  
M. N. Dieudonne ◽  
R. Pecquery ◽  
M. C. Leneveu ◽  
Y. Giudicelli
Keyword(s):  
Growth Factor ◽  
Dehydrogenase Activity ◽  
Sex Steroids ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
17Β Estradiol ◽  
Glycerol 3 Phosphate Dehydrogenase

Abstract To investigate the role of sex steroid hormones in adipose tissue development and distribution, we have studied the effect of various sex steroids (testosterone, dihydrotestosterone (DHT), and 17β-estradiol) in vitro, on the proliferation and differentiation processes in rat preadipocytes from deep (epididymal and parametrial) and superficial (femoral sc) fat deposits. All added steroids failed to affect the growth rate of preadipocytes from male rats when determined from day 1 to day 4 after plating, whether FCS was present or not in the culture medium. In contrast, in preadipocytes from female rats, we observed a positive effect (×2) of 17β-estradiol (0.01μ m) on the proliferative capacities of sc but not parametrial preadipocytes. When preadipocytes were exposed to testosterone or DHT (0.1 μm) during the differentiation process, the glycerol 3-phosphate dehydrogenase activity was significantly decreased in epididymal preadipocytes only. When preadipocytes from male rats were exposed to 17β-estradiol (0.01μ m), the differentiation capacities of preadipocytes were not modified. However, in parametrial preadipocytes from ovariectomized female rats, 17β-estradiol significantly increased (×1.34) the glycerol 3-phosphate dehydrogenase activity. In differentiated preadipocytes that had been exposed to sex steroids, expression of peroxisome proliferator-activated receptor γ2 was up-regulated by 17β-estradiol but not by androgens. As described in other cell types, sex steroids modulate insulin growth factor 1 receptor (IGF1R) expression in preadipocytes. Indeed, IGF1R levels were either enhanced by 17 β-estradiol (0.01 μm) in sc preadipocytes from female ovariectomized rats or decreased by DHT (0.01 μm) in epididymal preadipocytes. These effects were reversed by simultaneous exposure to androgen or estrogen receptor antagonists. In conclusion, this study demonstrates that, in rat preadipocytes kept in primary culture and chronically exposed to sex hormones, androgens elicit an antiadipogenic effect, whereas estrogens behave as proadipogenic hormones. Moreover, our results suggest that these opposite effects could be related to changes in IGF1R (androgens and estrogens) and peroxisome proliferator-activated receptor γ2 expression (estrogens).

scholarly journals Sex Difference in Hepatic Peroxisome Proliferator-Activated Receptor α Expression: Influence of Pituitary and Gonadal Hormones

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 101-109 ◽  
Author(s):  
Masoumeh Jalouli ◽  
Linda Carlsson ◽  
Caroline Améen ◽  
Daniel Lindén ◽  
Anna Ljungberg ◽  
...  
Keyword(s):  
Sex Difference ◽  
Gonadal Hormones ◽  
Female Rats ◽  
Male Rats ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Gh Treatment ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Secretory Pattern

Abstract Peroxisome proliferator-activated receptor (PPAR) α is a nuclear receptor that is mainly expressed in tissues with a high degree of fatty acid oxidation such as liver, heart, and skeletal muscle. Unsaturated fatty acids, their derivatives, and fibrates activate PPARα. Male rats are more responsive to fibrates than female rats. We therefore wanted to investigate if there is a sex difference in PPARα expression. Male rats had higher levels of hepatic PPARα mRNA and protein than female rats. Fasting increased hepatic PPARα mRNA levels to a similar degree in both sexes. Gonadectomy of male rats decreased PPARα mRNA expression to similar levels as in intact and gonadectomized female rats. Hypophysectomy increased hepatic PPARα mRNA and protein levels. The increase in PPARα mRNA after hypophysectomy was more pronounced in females than in males. GH treatment decreased PPARα mRNA and protein levels, but the sex-differentiated secretory pattern of GH does not determine the sex-differentiated expression of PPARα. The expression of PPARα mRNA in heart or soleus muscle was not influenced by gender, gonadectomy, hypophysectomy, or GH treatment. In summary, pituitary-dependent hormones specifically regulate hepatic PPARα expression. Sex hormones regulate the sex difference in hepatic PPARα levels, but not via the sexually dimorphic GH secretory pattern.

scholarly journals Neoplastic and Non-neoplastic Changes in F-344 Rats Treated with Naveglitazar, a γ-Dominant PPAR α/γ Agonist

2009 ◽  
Vol 37 (6) ◽  
pp. 741-753 ◽  
Author(s):  
Gerald G. Long ◽  
Vincent L. Reynolds ◽  
L. Wayne Dochterman ◽  
Thomas E. Ryan
Keyword(s):  
Adipose Tissue ◽  
Bladder Neoplasms ◽  
Urinary Bladder Neoplasms ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Associated Lesions ◽  
Histologic Types

The carcinogenic potential of naveglitazar, a γ-dominant peroxisome proliferator-activated receptor (PPAR) α/γ dual agonist, was evaluated in a two-year study in F344 rats (0, 0.3, 1.0, or 3.0 mg/kg, males; 0, 0.1, 0.3, or 1.0 mg/kg, females). Increased mortality in male rats of the high-dose group was related to cardiac-associated lesions, neoplasms, and undetermined causes. Degeneration and hypertrophy of the myocardium occurred with dose-responsive increased incidence and severity. Neoplasms with increased incidence included sarcomas in male rats and urinary bladder neoplasms in female rats. Most sarcomas in male rats occurred in the adipose tissue of the subcutis and were diagnosed as fibrosarcomas, with fewer liposarcomas and other histologic types. Non-neoplastic changes in adipose tissue included expansion of adipose tissue in multiple sites, alterations in cytoplasmic vesicular pattern in brown and white fat, increases in stroma and mesenchymal cells, and fibrosis. The severity of chronic progressive nephropathy was decreased in a dose-responsive manner in males, and hyperplasia and neoplasia of the mammary gland were decreased in incidence in females. The adverse effects of cardiotoxicity and increased incidence of neoplasms occurred with dose-responsive incidence and/or severity, and a no-effect level for these effects was not achieved in this study.

scholarly journals 17β-Estradiol restores excitability of a sexually dimorphic subset of myelinated vagal afferents in ovariectomized rats

2009 ◽  
Vol 297 (3) ◽  
pp. C654-C664 ◽  
Author(s):  
Guo-Fen Qiao ◽  
Bai-Yan Li ◽  
Yan-Jie Lu ◽  
Yi-Li Fu ◽  
John H. Schild
Keyword(s):  
Estrogen Receptor ◽  
Neuronal Excitability ◽  
Vagal Afferents ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Cellular Mechanisms ◽  
Patch Clamp Technique ◽  
17Β Estradiol ◽  
Vagal Afferent

We recently identified a myelinated vagal afferent subpopulation (Ah type) far more prevalent in female than male rats and showed that this difference extends to functionally specific visceral sensory afferents, baroreceptors of the aortic arch. Excitability of myelinated Ah-type afferents is markedly reduced after ovariectomy (OVX). Here we tested the hypothesis that 17β-estradiol can selectively restore excitability of these sex-specific vagal afferents. Acutely isolated vagal afferent neurons (VGN) from intact and OVX adult female rats were used with patch-clamp technique and current-clamp protocols to assess the effect of acute application of 17β-estradiol on neuronal excitability. At over physiologically relevant 17β-estradiol concentrations for rat (1–10 nM) excitability of myelinated Ah-type vagal afferents is restored to discharge frequencies comparable to those in intact females, albeit with some interesting differences related to burst and sustained patterns of neuronal discharge. Restoration of excitability occurs within 3 min of hormone application and is stereo specific, because 1,000 nM 17α-estradiol fails to alter excitability. Furthermore, activation of G protein-coupled estrogen receptor GPR30 with highly selective agonist G-1 similarly restores excitability of Ah-type afferents. The effectiveness of 17β-estradiol and G-1 is completely eliminated by application of high-affinity estrogen receptor ligand ICI-182,780. 17β-Estradiol conjugated with BSA is ∼70% as effective as 17β-estradiol alone in restoring Ah-type VGN excitability. These data support our conclusions that the cellular mechanisms leading to rapid restoration of neuronal excitability of myelinated Ah-type VGN after OVX occur, at least in part, via membrane-bound estrogen receptors. We contend that recovery of high-frequency discharge at physiologically relevant 17β-estradiol concentrations implies that this unique subtype of low-threshold myelinated vagal afferent may account for some of the sex-related differences in visceral organ system function. Sex differences in cardiovascular and gastrointestinal function and the potential role of GPR30 in modulation of sex-specific myelinated Ah-type vagal afferents are discussed.

Proteomic study of periovarian adipose tissue in 17β-estradiol-treated and untreated ovariectomized rats

2016 ◽  
Vol 94 (2) ◽  
pp. 167-175 ◽  
Author(s):  
Emilia Amengual-Cladera ◽  
Gabriela Capllonch-Amer ◽  
Isabel Lladó ◽  
Magdalena Gianotti ◽  
Ana M. Proenza
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Function ◽  
Corn Oil ◽  
Ovariectomized Rats ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Inflammatory Protein ◽  
17Β Estradiol

Taking into account the sexual dimorphism previously found in white adipose tissue (WAT) regarding mitochondrial function and biogenesis, as well as insulin sensitivity, the aim of this study was to go further into the role of sex hormones in this dimorphism. To achieve this objective, we used ovariectomized rats and performed a screening by means of proteomic analyses of the periovarian WAT, combined with a study of the protein levels of specific factors involved in mitochondrial function. Rats were ovariectomized at 5 weeks of age and subcutaneously injected every 48 h with corn-oil (OVX group) or with 17β-estradiol (E2, 10 μg/kg body mass; OVX + E2 group) for 4 weeks prior to sacrifice. Beside proteomic analysis, protein levels of Transcription Factor A, Mitochondrial (TFAM), cytochrome oxidase (COX)II, and COXIV were determined by Western blot, and mRNA levels of peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, ERα, ERβ, lipoprotein lipase (LPL), peroxisome proliferator-activated receptor-γ (PPARγ), and adiponectin were quantified by real-time PCR. Our results show that ovariectomy leads to an increase in anabolic processes and inflammatory protein levels as well as to a decrease in some of the markers of mitochondrial function, which are restored, at least in part, by E2 supplementation. Indeed, this E2 supplementation seems to be counteracted by a decline in ERα and in the ERα to ERβ ratio values that could be directed to avoid an over-stimulation of the E2 signaling pathway, given the possibility of an activation of extra-gonadal steroid biosynthetic pathways.

The role of sex steroids in the formation of sex-differentiated concentrations of corticosteroid-binding globulin in rats

1992 ◽  
Vol 132 (2) ◽  
pp. 235-240 ◽  
Author(s):  
G. D. Mataradze ◽  
R. M. Kurabekova ◽  
V. B. Rozen
Keyword(s):  
Sex Steroids ◽  
Testosterone Propionate ◽  
Mature Female ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Adult Males ◽  
Short Period ◽  
Corticosteroid Binding Globulin

ABSTRACT The role of sex steroids in the programming of the level of serum corticosteroid-binding globulin (CBG) in the rat has been studied at different stages of ontogenesis. The CBG content in the serum of mature female rats was 2·5 times higher than that in male rats. Sexual dimorphism of CBG content was absent in immature animals of 3–4 weeks of age. Castration of mature rats led to a 40–50% increase in CBG content. The CBG concentration in mature females or castrated adult males treated with testosterone propionate (TP; 3 mg/day for 4 days) was decreased by 40–50% compared with vehicle-treated rats. Oestradiol injection (1 μg/day for 4 days) had no influence on CBG levels in mature male and ovariectomized adult female rats. Immature rats were castrated on days 1, 7, 14, 21, 28 or 35 of age and the CBG level was determined at 10–12 weeks of age. The CBG content of rats castrated up to day 28 of age was 2·5 times higher than that in mature males and did not differ from that in mature females. The CBG content of male rats castrated on day 35 of age was the same as that of adult castrated males. The CBG level in castrated rats treated with TP (1·25 mg for days 1–3 or 300 μg/day for 5 days after castration at day 7 up to day 26) did not differ from that in controls (i.e. vehicle-treated rats). TP injection into castrated rats on days 29–33 of age (300 μg/day) led to a 40–50% decrease in CBG level when compared with controls. Ovariectomy of rats at different ages (on days 1 or 28 or 3 months) did not affect CBG concentration. TP injection (300 μg/day) into ovariectomized rats on days 29–33 had the same effect on CBG concentration as in males. Gonadectomized rats treated with diethylstilboestrol on days 29–33 (100 μg/day) had the same CBG concentrations as TP-treated rats. It was concluded that there is a short period during ontogenesis, from days 29 to 35 of age, which is critical for irreversible masculinization of the CBG concentration in male rats. Journal of Endocrinology (1992) 132, 235–240

scholarly journals Gonadal Steroids Differentially Regulate the Messenger Ribonucleic Acid Expression of Pituitary Orexin Type 1 Receptors and Adrenal Orexin Type 2 Receptors

Endocrinology ◽  
2003 ◽  
Vol 144 (4) ◽  
pp. 1219-1225 ◽  
Author(s):  
Olaf Jöhren ◽  
Norbert Brüggemann ◽  
Andreas Dendorfer ◽  
Peter Dominiak
Keyword(s):  
Gonadal Steroids ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Mrna Levels ◽  
Receptor Mrna ◽  
Male And Female Rats ◽  
17Β Estradiol

Abstract Hypothalamic prepro-orexin as well as pituitary and adrenal orexin receptors are gender-specifically expressed. To assess the regulation by gonadal steroids, we investigated the effect of 17β-estradiol in female and of testosterone in male rats on prepro-orexin and orexin receptor mRNA expression. Rats were either sham-operated or gonadectomized and subsequently treated with placebo, 17β-estradiol, or testosterone for 21 d. Tissue mRNA levels of prepro-orexin, orexin type-1 (OX1), and orexin type-2 (OX2) receptors were measured using quantitative real-time RT-PCR. In female rats, pituitary OX1 receptor mRNA levels were increased 12-fold after ovariectomy compared with sham- operated rats. The increase of pituitary OX1 receptor mRNA was inhibited by treatment with 17β-estradiol. Adrenal mRNA levels of OX2 receptors in ovariectomized rats were increased 2-fold compared with sham-operated rats and were also reduced by treatment with 17β-estradiol. In male rats, orchidectomy increased the mRNA levels of pituitary OX1 receptors compared with sham-operated rats. In contrast, adrenal OX2 receptor mRNA was reduced after orchidectomy. Testosterone treatment reversed the effect of orchidectomy on pituitary OX1 and adrenal OX2 receptors. In the hypothalamus, no differences were found in the mRNA levels of prepro-orexin, OX1, and OX2 receptors between sham-operated, placebo-treated, and steroid-treated female or male rats. Our results indicate that gonadal steroids differentially regulate pituitary OX1 receptors and adrenal OX2 receptors in male and female rats and may contribute to specific sex- dependent neuroendocrine and endocrine actions of orexins.

scholarly journals Adverse Adipose Phenotype and Hyperinsulinemia in Gravid Mice Deficient in Placental Growth Factor

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2176-2183 ◽  
Author(s):  
Bianca Hemmeryckx ◽  
Rita van Bree ◽  
Berthe Van Hoef ◽  
Lisbeth Vercruysse ◽  
H. Roger Lijnen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Adrenergic Receptors ◽  
Growth Factor Receptor ◽  
Placental Growth Factor ◽  
Peroxisome Proliferator ◽  
Vascular Endothelial ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adipocyte Hypertrophy ◽  
Endothelial Growth Factor

Pregnancy-induced metabolic changes are regulated by signals from an expanded adipose organ. Placental growth factor (PlGF), acting through vascular endothelial growth factor receptor-1, may be among those signals. There is a steep rise in circulating PlGF during normal pregnancy, which is repressed in gravidas who develop preeclampsia. PlGF-deficiency in mice impairs adipose vascularization and development. Here we studied young-adult PlGF-deficient (PlGF−/−) and wild-type mice on a high-fat diet in the nongravid state and at embryonic day (E) 13.5 or E18.5 of gestation. Litter size and weight were normal, but E18.5 placentas were smaller in PlGF−/− pregnancies. PlGF−/− mice showed altered intraadipose dynamics, with the following: 1) less blood vessels and fewer brown, uncoupling protein (UCP)-1-positive, adipocytes in white sc and perigonadal fat compartments and 2) white adipocyte hypertrophy. The mRNA expression of β3-adrenergic receptors, peroxisome proliferator-activated receptor-γ coactivator-1α, and UCP-1 was decreased accordingly. Moreover, PlGF−/− mice showed hyperinsulinemia. Pregnancy-associated changes were largely comparable in PlGF−/− and wild-type dams. They included expanded sc fat compartments and adipocyte hypertrophy, whereas adipose expression of key angiogenesis/adipogenesis (vascular endothelial growth factor receptor-1, peroxisome proliferator-activated receptor-γ2) and thermogenesis (β3-adrenergic receptors, peroxisome proliferator-activated receptor-γ coactivator-1α, and UCP-1) genes was down-regulated; circulating insulin levels gradually increased during pregnancy. In conclusion, reduced adipose vascularization in PlGF−/− mice impairs adaptive thermogenesis in favor of energy storage, thereby promoting insulin resistance and hyperinsulinemia. Pregnancy adds to these changes by PlGF-independent mechanisms. Disturbed intraadipose dynamics is a novel mechanism to explain metabolic changes in late pregnancy in general and preeclamptic pregnancy in particular.

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