Sex has a role in the incidence and outcome of neurological illnesses, also influencing the response to treatments. Neuroinflammation is involved in the onset and progression of several neurological diseases, and the fact that estrogens have anti-inflammatory activity suggests that these hormones may be a determinant in the sex-dependent manifestation of brain pathologies. We describe significant differences in the transcriptome of adult male and female microglia, possibly originating from perinatal exposure to sex steroids. Microglia isolated from adult brains maintain the sex-specific features when put in culture or transplanted in the brain of the opposite sex. Female microglia are neuroprotective because they restrict the damage caused by acute focal cerebral ischemia. This study therefore provides insight into a distinct perspective on the mechanisms underscoring a sexual bias in the susceptibility to brain diseases.

Sex characteristics

Sexual Differentiation

Sexual dimorphism

10.1016/j.celrep.2018.05.048

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Citations (484)

An Essential Role for Liver ERα in Coupling Hepatic Metabolism to the Reproductive Cycle

Cell Reports (2016)

Sara Della Torre Nico Mitro Roberta Fontana Monica Gomaraschi Elda Favari

Lipoprotein synthesis is controlled by estrogens, but the exact mechanisms underpinning this regulation and the role of the hepatic estrogen receptor α (ERα) in cholesterol physiology are unclear. Utilizing a mouse model involving selective ablation of ERα in the liver, we demonstrate that hepatic ERα couples lipid metabolism to the reproductive cycle. We show that this receptor regulates the synthesis of cholesterol transport proteins, enzymes for lipoprotein remodeling, and receptors for cholesterol uptake. Additionally, ERα is indispensable during proestrus for the generation of high-density lipoproteins efficient in eliciting cholesterol efflux from macrophages. We propose that a specific interaction with liver X receptor α (LXRα) mediates the broad effects of ERα on the hepatic lipid metabolism.

Reproductive cycle

10.1016/j.celrep.2016.03.019

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Citations (114)

Effects of Vitis vinifera L. leaves extract on UV radiation damage in human keratinocytes (HaCaT)

Journal of Photochemistry and Photobiology B Biology (2020)

Laura Marabini Gloria Melzi Federica Lolli Mario Dell’Agli Stefano Piazza

HaCaT

Comet Assay

10.1016/j.jphotobiol.2020.111810

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Citations (48)

UV-A and UV-B damage: the protective effect of Vitis vinifera L. extract on HaCaT cell line

Toxicology Letters (2018)

Federica Lolli

HaCaT

10.1016/j.toxlet.2018.06.756

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Citations (0)

Sexual Dimorphism and Estrogen Action in Mouse Liver

Advances in experimental medicine and biology (2017)

Sara Della Torre Federica Lolli Paolo Ciana Adriana Maggi

Sexual dimorphism

Estrogen receptor alpha

Pathophysiology

Estrogen receptor beta

10.1007/978-3-319-70178-3_8

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Citations (21)

Short-Term Fasting Reveals Amino Acid Metabolism as a Major Sex-Discriminating Factor in the Liver

Cell Metabolism (2018)

Sara Della Torre Nico Mitro Clara Meda Federica Lolli Silvia Pedretti

Sex impacts on liver physiology with severe consequences for energy metabolism and response to xenobiotic, hepatic, and extra-hepatic diseases. The comprehension of the biology subtending sex-related hepatic differences is therefore very relevant in the medical, pharmacological, and dietary perspective. The extensive application of metabolomics paired to transcriptomics here shows that, in the case of short-term fasting, the decision to maintain lipid synthesis using amino acids (aa) as a source of fuel is the key discriminant for the hepatic metabolism of male and female mice. Pharmacological and genetic interventions indicate that the hepatic estrogen receptor (ERα) has a key role in this sex-related strategy that is primed around birth by the aromatase-dependent conversion of testosterone into estradiol. This energy partition strategy, possibly the result of an evolutionary pressure enabling mammals to tailor their reproductive capacities to nutritional status, is most important to direct future sex-specific dietary and medical interventions.

10.1016/j.cmet.2018.05.021

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Citations (129)

Hepatic ERα accounts for sex differences in the ability to cope with an excess of dietary lipids

Molecular Metabolism (2019)

Clara Meda Mara Barone Nico Mitro Federica Lolli Silvia Pedretti

Among obesity-associated metabolic diseases, non-alcoholic fatty liver disease (NAFLD) represents an increasing public health issue due to its emerging association with atherogenic dyslipidemia and cardiovascular diseases (CVDs). The lower prevalence of NAFLD in pre-menopausal women compared with men or post-menopausal women led us to hypothesize that the female-inherent ability to counteract this pathology might strongly rely on estrogen signaling. In female mammals, estrogen receptor alpha (ERα) is highly expressed in the liver, where it acts as a sensor of the nutritional status and adapts the metabolism to the reproductive needs. As in the male liver this receptor is little expressed, we here hypothesize that hepatic ERα might account for sex differences in the ability of males and females to cope with an excess of dietary lipids and counteract the accumulation of lipids in the liver.Through liver metabolomics and transcriptomics we analyzed the relevance of hepatic ERα in the metabolic response of males and females to a diet highly enriched in fats (HFD) as a model of diet-induced obesity.The study shows that the hepatic ERα strongly contributes to the sex-specific response to an HFD and its action accounts for opposite consequences for hepatic health in males and females.This study identified hepatic ERα as a novel target for the design of sex-specific therapies against fatty liver and its cardio-metabolic consequences.

10.1016/j.molmet.2019.12.009

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Citations (63)

The IGF Axis in Prostate Cancer

Current Pharmaceutical Design (2007)

Salvatore Monti Laura Proietti-Pannunzi Alessandro Sciarra Federica Lolli Paolo Falasca

Prostate cancer, the most frequent non-cutaneous malignancy in men from industrialized countries, is a growing medical problem, representing the second leading cause of male cancer deaths. In the last decade, converging evidence from epidemiological and biological studies suggests that the Insulin-like Growth Factor (IGF) axis is involved in the tumorigenesis and neoplastic growth of prostate cancer. Epidemiological observations indicated that circulating IGF-I levels are positively associated with the increased risk of prostate cancer. The activation of type I IGF receptor (IGF-IR) by IGFI and/or IGF-II, has mitogenic and antiapoptotic effects on normal and malignant prostate cells. Altered expression of IGF axis components has also been reported in vitro and in animal models of prostate cancer, as well as in human prostate cancer tissue samples. In this review we address and analyze epidemiological studies, in vitro and in vivo cancer models, and human ex vivo prostate cancer researches performed to date supporting the role of IGF axis in prostate cancer.

10.2174/138161207780249128

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Citations (44)