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. 2018 Sep 12;9:1027. doi: 10.3389/fphar.2018.01027

FIGURE 8.

FIGURE 8

Proposed model for placental glucocorticoid (cortisol) function and metabolism. For detailed description, see text. Cortisol can diffuse across cell membranes and regulate target protein expression directly via glucocorticoid receptor (GR) or indirectly via other transcription factors (e.g., Sp1). Placental corticotropin-releasing hormone (CRH) is the major mediator of adaptive response to stressors during pregnancy. Cortisol stimulates placental CRH expression, which regulates placental hormone levels (e.g., hCG, estrogen, progesterone, and 11β-HSD2). Red arrows indicate inhibiting/negative feedback pathways, while green arrows indicate stimulating pathways. ABC transporters, ATP-binding cassette transporters; ACTH, adrenocorticotropic hormone; CRH, corticotropin-releasing hormone; DHEA, dehydroepiandrosterone; GRE, glucocorticoid response element; HSD, hydroxysteroid dehydrogenase; hCG, human chorionic gonadotropin; pFEC, placental-fetal endothelial cell; PKA, protein kinase A; Sp1, specificity protein 1 transcription factor; STB, syncytiotrophoblast.