A single dose of dihydrotestosterone induced a myogenic transcriptional program in female intra-abdominal adipose tissue

Giorgio, Maria Rita De; Yoshioka, Mayumi; St‐Amand, Jonny

doi:10.1016/j.jsbmb.2010.02.023

Cited by 5 publications

(4 citation statements)

References 49 publications

(67 reference statements)

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“…To investigate the effect of androgen treatment in the steroid-depleted mouse uterus, we treated ovx mice with DHT at a supraphysiological dose (0.2 mg/mouse) previously shown to elicit uterine responses ( 29 , 33 ). Although the DHT concentrations generated in our experimental conditions are above the physiological levels detected in cycling female mice ( 6 ), this dose is consistent with those used in several previous studies investigating the direct action of DHT in the rodent uterus ( 22 , 34 ) and adipose tissue ( 29 , 35 ).…”

Section: Discussionsupporting

confidence: 89%

A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus

et al. 2016

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The endometrium consists of stromal and epithelial compartments (luminal and glandular) with distinct functions in the regulation of uterine homeostasis. Ovarian sex steroids, namely 17β-estradiol and progesterone, play essential roles in modulating uterine cell proliferation, stromal-epithelial cross-talk and differentiation in preparation for pregnancy. The effect of androgens on uterine function remains poorly understood. The current study investigated the effect of the non-aromatizable androgen dihydrotestosterone (DHT) on mouse endometrial function. Ovx female mice were given a single sc injection (short treatment) or 7 daily injections (long treatment) of vehicle alone (5% ethanol, 0.4% methylcellulose) or vehicle with the addition of 0.2 mg DHT (n=8/group) and a single injection of bromodeoxyuridine 2 hours prior to tissue recovery. Treatment with DHT increased uterine weight, the area of the endometrial compartment and immunoexpression of the androgen receptor in the luminal and glandular epithelium. Treatment-dependent proliferation of epithelial cells was identified by immunostaining for MKi67 and bromodeoxyuridine. Real-time PCR identified significant DHT-dependent changes in the concentrations of mRNAs encoded by genes implicated in the regulation of the cell cycle (Wee1, Ccnd1, Rb1) and stromal-epithelial interactions (Wnt4, Wnt5a, Wnt7a, Cdh1, Vcl, Igf1, Prl8, Prlr) as well as a striking effect on the number of endometrial glands. This study has revealed a novel role for androgens in regulating uterine function with an effect on the glandular compartment of the endometrium. This previously unrecognized role for androgens has implications for our understanding of the role of androgens in regulation of endometrial function and fertility in women.

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Section: Discussionsupporting

confidence: 89%

A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus

et al. 2016

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“…The mice in the two groups were housed individually in lighttight, ventilated closets under a 12-h/12-h LD cycle for 2 weeks. At the start of the second week during the LD cycle, mice in the DHT treatment group were injected subcutaneously with DHT (2 mg/kg body weight) every day at ZT12 (a total of seven injections), whereas the control mice were injected with a corresponding volume of sesame oil based on their body weights (37). After 2 weeks under the LD cycle, the mice were released into DD under free-running conditions.…”

Section: The Circadian Clock and Androgens Control Elovl3 Expressionmentioning

confidence: 99%

Coordination between the circadian clock and androgen signaling is required to sustain rhythmic expression of Elovl3 in mouse liver

Chen

Gao

Yang

et al. 2019

Journal of Biological Chemistry

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Edited by Qi-Qun Tang ELOVL3 is a very long-chain fatty acid elongase, and its mRNA levels display diurnal rhythmic changes exclusively in adult male mouse livers. This cyclical expression of hepatic Elovl3 is potentially controlled by the circadian clock, related hormones, and transcriptional factors. It remains unknown, however, whether the circadian clock, in conjunction with androgen signaling, functions in maintaining the rhythmic expression of Elovl3 in a sexually dimorphic manner. Under either zeitgeber or circadian time, WT mouse livers exhibited a robust circadian rhythmicity in the expression of circadian clock genes and Elovl3. In contrast, male Bmal1 ؊/؊ mice displayed severely weakened expression of hepatic circadian clock genes, resulting in relatively high, but nonrhythmic, Elovl3 expression levels. ChIP assays revealed that NR1D1 binds to the Elovl3 promoter upon circadian change in WT mouse livers in vivo, and a diminished binding was observed in male Bmal1 ؊/؊ mouse livers. Additionally, female mouse livers exhibited constant low levels of Elovl3 expression. Castration markedly reduced Elovl3 expression levels in male mouse livers but did not disrupt circadian variation of Elovl3. Injection of female mice with 5␣-dihydrotestosterone induced Elovl3 rhythmicity in the liver. In AML12 cells, 5␣-dihydrotestosterone also elevated Elovl3 expression in a time-dependent manner. In contrast, flutamide efficiently attenuated this induction effect. In conclusion, a lack of either the circadian clock or androgen sig-naling impairs hepatic Elovl3 expression, highlighting the observation that coordination between the circadian clock and androgen signaling is required to sustain the rhythmic expression of Elovl3 in mouse liver. Elovl3 (elongation of very long-chain fatty acids 3), also known as Cig30, was initially identified as a thermogenesisrelated gene after its expression in brown adipose tissue was found to be highly elevated in response to cold stimulation (1). Accumulating reports indicate that significant Elovl3 expression also occurs in white adipose tissue, liver, and triglyceriderich glands, such as the sebaceous and meibomian glands (2-5). As a member of the Elovl gene family, Elovl3 encodes an enzyme that functions in the synthesis of C20-C24 saturated and mono-unsaturated very long-chain fatty acids (VLCFAs). 5 It was previously demonstrated that Elovl3 Ϫ/Ϫ mice exhibit a clear skin phenotype with an impaired barrier function resulting from changes in the synthesis of C20-C24 saturated and mono-unsaturated VLCFAs, triglyceride synthesis, and sebum formation (5). Male Elovl3 Ϫ/Ϫ mice also display a diminished capacity to accumulate fat within brown adipose tissue (6). Additionally, male and female Elovl3 Ϫ/Ϫ mice possess reduced hepatic lipogenic gene expression and triglyceride content and are also resistant to diet-induced obesity (7). These findings indicate that ELOVL3 acts as an important regulator of triglyceride and lipid droplet formation in skin, adipose tissue, and liver. To further det...

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“…Meanwhile, testosterone is an important regulator of fat mass and distribution in males [9,10]. In females, however, DHT induces a myogenic transcriptional program in intra-abdominal adipose tissue [32] as well as formation of typical polycystic ovaries with increased apoptotic follicles in rats [33]. Specifically, DHT-treated rats develop obesity with enlarged adipocyte size and insulin resistance, indicating that increased androgen levels may induce alteration of body composition as well as reduction of insulin sensitivity [33].…”

Section: Discussionmentioning

confidence: 99%

Sex Hormones Regulate Hepatic Fetuin Expression in Male and Female Rats

Kim

Choi

Lee

et al. 2014

Cell Physiol Biochem

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Background: To date, there are limited studies on the sex-specific relationship between fetuins (Ft-A and Ft-B) and metabolic diseases. Our recent proteomic study has shown that fetuins may play sex-dependent roles in obesity and diabetes. In the present study, we investigated the expression of hepatic fetuins with respect to the effects of sex hormones both in vivo and in vitro. Methods & Results: A sex hormone-treated rat model was established in order to study the effects of sex hormones on hepatic fetuin expression. Animal experiments revealed that 17β-estradiol (E2)- and dihydrotestosterone (DHT)-treated rats showed opposite effects in terms of body weight gain in both genders. Interestingly, Ft-A and Ft-B were sex-dependently expressed in the livers of rats, responding to different regulatory modes of sex hormone receptors (ERα, ERβ, and AR). To validate in vivo data, rat normal liver cells were treated with E2 or DHT at different concentrations, and similar expression patterns as those in the animal-based experiments were confirmed. We found that these changes were mediated via sex hormone receptors using antagonist experiments. Conclusion: The results of the present study indicate that sex hormones induce gender-dimorphic expression of hepatic fetuins directly via sex hormone receptors. To the best of our knowledge, this is the first approach to address the effects of sex hormones on hepatic fetuin expression.

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A single dose of dihydrotestosterone induced a myogenic transcriptional program in female intra-abdominal adipose tissue

Cited by 5 publications

References 49 publications

A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus

A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus

Coordination between the circadian clock and androgen signaling is required to sustain rhythmic expression of Elovl3 in mouse liver

Sex Hormones Regulate Hepatic Fetuin Expression in Male and Female Rats

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