Glucocorticoid Sexual Dimorphism in Metabolism: Dissecting the Role of Sex Hormones. (May 2020)

• Record Type: Journal Article
• Authors: Kroon, Jan; Pereira, Alberto M.; Meijer, Onno C.
• Is Part Of: Trends in endocrinology and metabolism. Volume 31:Number 5(2020)
• Page Start: 357
• Page End: 367
• Publication Date: 2020-05
• Subjects: androgens -- estrogens -- Cushing's syndrome -- glucocorticoids -- sexual dimorphism; Endocrinology -- Periodicals; Metabolism -- Periodicals; Metabolism; 616.4
• DOI: 10.1016/j.tem.2020.01.010
• Languages: English
• ISSNs: 1043-2760

Abstract

Abstract : Glucocorticoids are steroid hormones that are of pivotal importance in human physiology. Glucocorticoid signaling is complex in nature and dependent on many interacting factors. As glucocorticoids exhibit sexually dimorphic effects on several key processes including in metabolism, crosstalk with the sex steroid hormones (androgens and estrogens) is relevant. In this review, we highlight the state-of-the-art knowledge on glucocorticoid sexual dimorphism and sex hormone crosstalk. We include current insight in the molecular mechanisms that underlie nuclear steroid receptor crosstalk, and sex hormone effects on glucocorticoid metabolism. Finally, we show how these findings translate to humans exposed to excess glucocorticoid signaling, and we propose future avenues in the emerging field of steroid hormone crosstalk. Highlights: Preclinical evidence shows that glucocorticoids have sexually dimorphic effects on metabolism in mice. Glucocorticoid-induced metabolic adverse effects like hyperinsulinemia and insulin resistance in mice are lost upon androgen deficiency. Receptors for androgens and estrogens can modulate transcriptional regulation by glucocorticoid receptors. Androgens and estrogens influence enzymatic regeneration of glucocorticoids by regulating 11β-HSD1 activity. Sexual dimorphism exists in the symptoms that patients with Cushing's disease develop as a consequence of their hypercortisolism.