The adrenal cortex synthesizes steroid hormones that have a central role in coordinating the organism’s homeostasis, as part of the hypothalamic–pituitary–adrenal (HPA) axis and the renin–angiotensin–aldosterone system (RAAS). Although the importance of analyzing both sexes in biological studies has been overlooked in the past, the situation has been changing during the last ten years, and many major funding bodies now request that the impact of sex and gender are part of all relevant studies. In other cases, sexual dimorphism of mammalian traits has sex chromosome-related causes, such as the incomplete inactivation of X chromosome genes. Many of the differences between males and females stem from the action of gonadal hormones, affecting stem cell activity, immune system activation, stromal compartments, and systemic metabolism. According to systematic phenotypic analysis of genetically modified mouse lines, sex is a major variable that determines a large proportion of mammalian phenotypic traits. While women are more susceptible to autoimmune diseases, men show higher incidence and worse prognosis in a wide range of cancers. Many human diseases of nonreproductive organs display sex bias.
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