Developmental androgenization programs metabolic dysfunction in adult mice

Mauvais-Jarvis, Franck

doi:10.4161/adip.27746

Cited by 16 publications

(12 citation statements)

References 41 publications

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“…In mice and rats, developmental plasticity of hypothalamic circuits controlling energy balance and peripheral adipose tissue development occur during the first two weeks of neonatal life (Ailhaud et al, 1992; Bouret et al, 2004; Gesta et al, 2007). Therefore, with regard to sexual differentiation of the hypothalamus and development of adipose tissue, the mouse first week of neonatal life parallels human fetal development during the second trimester of pregnancy (Mauvais-Jarvis, 2014). This later window of neonatal developmental plasticity in the mouse provides an experimental advantage that allows manipulation of the neonatal sex steroid milieu in the presence or absence of androgen receptor (AR) or/and estrogen receptors (ERs).…”

Section: Methods For the Study Of Sex Differences In Preclinical Studmentioning

confidence: 99%

“…This suggests interactions between perinatal testosterone and complements of sex-linked genes in sex differentiation of metabolic homeostasis. Finally, although some traits of metabolic programming by testosterone in females are typical of masculinization, others are inconsistent with masculinization (Mauvais-Jarvis, 2014). …”

Section: Methods For the Study Of Sex Differences In Preclinical Studmentioning

confidence: 99%

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A Guide for the Design of Pre-clinical Studies on Sex Differences in Metabolism

2017

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In animal models, the physiological systems involved in metabolic homeostasis exhibit a sex difference. Investigators often use male rodents because they show metabolic disease better than females. Thus, females are not used precisely because of an acknowledged sex difference that represents an opportunity to understand novel factors reducing metabolic disease more in one sex than the other. The National Institutes of Health (NIH) mandate to consider sex as a biological variable in preclinical research places new demands on investigators and peer reviewers who often lack expertise in model systems and experimental paradigms used in the study of sex differences. This review discusses experimental design and interpretation in studies addressing the mechanisms of sex differences in metabolic homeostasis and disease, using animal models and cells. We also highlight current limitations in research tools and attitudes that threaten to delay progress in studies of sex differences in basic animal research.

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Section: Methods For the Study Of Sex Differences In Preclinical Studmentioning

confidence: 99%

Section: Methods For the Study Of Sex Differences In Preclinical Studmentioning

confidence: 99%

A Guide for the Design of Pre-clinical Studies on Sex Differences in Metabolism

2017

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“…Thus, like the hypothalamic control of reproduction, the hypothalamic control of energy homeostasis could be programmed or defeminized as well as masculinized by the perinatal testicular testosterone surge in males. In fact, evidence suggests that this is the case for the hypothalamic melanocortin system, at least in mice [ 31 , 65 , 66 ]. Indeed, when female mice are neonatally androgenized with testosterone (as males are normally by the testicular testosterone surge), these neonatally androgenized females exhibit a masculinized POMC neuronal architecture in the hypothalamic arcuate nucleus in adults as is observed in littermate adult males [ 31 ].…”

Section: Reviewmentioning

confidence: 99%

Sex differences in metabolic homeostasis, diabetes, and obesity

2015

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There are fundamental aspects of the control of metabolic homeostasis that are regulated differently in males and females. This sex asymmetry represents an evolutionary paradigm for females to resist the loss of energy stores. This perspective discusses the most fundamental sex differences in metabolic homeostasis, diabetes, and obesity. Together, the role of genetic sex, the programming effect of testosterone in the prenatal period in males, and the activational role of sex hormones at puberty produce two different biological systems in males and females that need to be studied separately. These sex-specific differences in energy homeostasis and metabolic dysfunction represent an untested source of factors that can be harnessed to develop relevant sex-based therapeutic avenues for diabetes, metabolic syndrome, and obesity.

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“…In a meta-analysis of five Selective Estrogens, Menopause, and Response to Therapy (SMART) randomized control trials in postmenopausal women, bazedoxifene/CE treatment for 2 years prevented the increase in body weight and BMI observed in the placebo group [50]. Studies are ongoing to address the effect of bazedoxifene/CE in preventing metabolic dysfunction in obese postmenopausal women [51, 52]. …”

Section: The Effects Of Serms On Obesitymentioning

confidence: 99%

The effect of selective estrogen receptor modulators on type 2 diabetes onset in women: Basic and clinical insights

Lovre

Mauvais-Jarvis

2017

Journal of Diabetes and its Complications

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Selective estrogen receptor modulators (SERMs) are a class of compounds that interact with estrogen receptors (ERs) and exert agonist or antagonist effects on ERs in a tissue-specific manner. Tamoxifen, a first generation SERM, is used for treatment of ER positive breast cancer. Raloxifene, a second generation SERM, was used to prevent postmenopausal osteoporosis. The third-generation SERM bazedoxifene (BZA) effectively prevents osteoporosis while preventing estrogenic stimulation of breast and uterus. Notably, BZA combined with conjugated estrogens (CE) is a new menopausal treatment. The menopausal state predisposes to metabolic syndrome and type 2 diabetes, and therefore the effects of SERMs on metabolic homeostasis are gaining attention. Here, we summarize knowledge of SERMs’ impacts on metabolic, homeostasis, obesity and diabetes in rodent models and postmenopausal women.

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Developmental androgenization programs metabolic dysfunction in adult mice

Cited by 16 publications

References 41 publications

A Guide for the Design of Pre-clinical Studies on Sex Differences in Metabolism

A Guide for the Design of Pre-clinical Studies on Sex Differences in Metabolism

Sex differences in metabolic homeostasis, diabetes, and obesity

The effect of selective estrogen receptor modulators on type 2 diabetes onset in women: Basic and clinical insights

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