Stress, Sex, and Sugar: Glucocorticoids and Sex-Steroid Crosstalk in the Sex-Specific Misprogramming of Metabolism

• Authors: Daniel Ruiz, University of Chicago; Vasantha Padmanabhan, University of Michigan; Robert M. Sargis, University of Illinois
• Journal Title: Journal of the Endocrine Society
• Volume: Volume 4, Number 8
• Publisher: Endocrine Society | 2020-07-04
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1210/jendso/bvaa087
• Subjects: Biology, Molecular; Biology, Genetics; Health Sciences, Human Development; Health Sciences, Immunology
• Keywords: glucocorticoid; estrogen; androgen; progestogen; crosstalk; sex-specific; metabolism; diabetes; developmental programming; endocrine-disrupting chemicals

Abstract

Early-life exposures to environmental insults can misprogram development and increase metabolic disease risk in a sex-dependent manner by mechanisms that remain poorly characterized. Modifiable factors of increasing public health relevance, such as diet, psychological stress, and endocrine-disrupting chemicals, can affect glucocorticoid receptor signaling during gestation and lead to sex-specific postnatal metabolic derangements. Evidence from humans and animal studies indicate that glucocorticoids crosstalk with sex steroids by several mechanisms in multiple tissues and can affect sex-steroid–dependent developmental processes. Nonetheless, glucocorticoid sex-steroid crosstalk has not been considered in the glucocorticoid-induced misprogramming of metabolism. Herein we review what is known about the mechanisms by which glucocorticoids crosstalk with estrogen, androgen, and progestogen action. We propose that glucocorticoid sex-steroid crosstalk is an understudied mechanism of action that requires consideration when examining the developmental misprogramming of metabolism, especially when assessing sex-specific outcomes.