Do the Interactions between Glucocorticoids and Sex Hormones Regulate the Development of the Metabolic Syndrome?

Abstract

The metabolic syndrome is basically a maturity-onset disease. Typically, its manifestations begin to flourish years after the initial dietary or environmental aggression began. Since most hormonal, metabolic, or defense responses are practically immediate, the procrastinated response do not seem justified. Only in childhood, the damages of the metabolic syndrome appear with minimal delay. Sex affects the incidence of the metabolic syndrome, but this is more an effect of timing than absolute gender differences, females holding better than males up to menopause, when the differences between sexes tend to disappear. The metabolic syndrome is related to an immune response, countered by a permanent increase in glucocorticoids, which keep the immune system at bay but also induce insulin resistance, alter the lipid metabolism, favor fat deposition, mobilize protein, and decrease androgen synthesis. Androgens limit the operation of glucocorticoids, which is also partly blocked by estrogens, since they decrease inflammation (which enhances glucocorticoid release). These facts suggest that the appearance of the metabolic syndrome symptoms depends on the strength (i.e., levels) of androgens and estrogens. The predominance of glucocorticoids and the full manifestation of the syndrome in men are favored by decreased androgen activity. Low androgens can be found in infancy, maturity, advanced age, or because of their inhibition by glucocorticoids (inflammation, stress, medical treatment). Estrogens decrease inflammation and reduce the glucocorticoid response. Low estrogen (infancy, menopause) again allow the predominance of glucocorticoids and the manifestation of the metabolic syndrome. It is postulated that the equilibrium between sex hormones and glucocorticoids may be a critical element in the timing of the manifestation of metabolic syndrome-related pathologies.

Sex, the aging immune system, and chronic disease

“…Estrogen signaling through membrane-bound ERs has been shown to regulate arterial tone and blood pressure, as well as protect against vascular injury and atherosclerosis [123,124]. Estrogens influence metabolism indirectly by signaling to decrease food intake and favor energy expenditure, and to counteract the actions of excess glucocorticoids which have been implicated in the development of visceral obesity and insulin resistance [125][126][127]. Thus, it seems reasonable that estrogens contribute to the reduced risk of atherosclerosis and type 2 diabetes in women during the childbearing years through their effects on vascular tissue and metabolic processes, and that menopause enables the incidence of both chronic diseases to approach rates observed in men of the same age.…”

Neuronal basis of reproductive dysfunctions associated with diet and alcohol: From the womb to adulthood

“…Estradiol suppression of gonadotropin secretion is an essential component of the female reproductive cycle and estrogens suppress body weight by altering food intake and metabolism [100,101]. Ovarian estrogens exert anti-obesity effects in female mammals [102]. In postmenopausal women, lower estrogen levels are associated with obesity [103,104] and hormone replacement therapy reverses the progression of obesity and metabolic dysfunctions [105].…”

Sex- and age-specific associations between major depressive disorder and metabolic syndrome in two general population samples in Germany

“…Nevertheless, there are explanatory models that link MDD to metabolic alterations and MetS that could account for the revealed sex-and age-dependent results. In a review on endocrinological pathways that contribute to MetS, Alemany (58) postulated that MetS is a maturity-onset disease that results from the complex and age-and sex-specific interaction of sex hormones and glucocorticoids. She claimed that the sex differences (males are more often affected) and age effects (convergence of sex-specific prevalence rates in elderly) in MetS are predominantly an effect of age than sex differences per se.…”