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

Daniel RuizVasantha PadmanabhanRobert M Sargis
Published in: Journal of the Endocrine Society (2020)
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.
Keyphrases
  • public health
  • preterm infants
  • physical activity
  • gene expression
  • type diabetes
  • skeletal muscle
  • high glucose
  • air pollution
  • human health