| First Author | Watts D | Year | 2021 |
| Journal | Cell Mol Life Sci | Volume | 78 |
| Issue | 7 | Pages | 3577-3590 |
| PubMed ID | 33464382 | Mgi Jnum | J:306672 |
| Mgi Id | MGI:6705409 | Doi | 10.1007/s00018-020-03750-1 |
| Citation | Watts D, et al. (2021) HIF1alpha is a direct regulator of steroidogenesis in the adrenal gland. Cell Mol Life Sci 78(7):3577-3590 |
| abstractText | Endogenous steroid hormones, especially glucocorticoids and mineralocorticoids, derive from the adrenal cortex, and drastic or sustained changes in their circulatory levels affect multiple organ systems. Although hypoxia signaling in steroidogenesis has been suggested, knowledge on the true impact of the HIFs (Hypoxia-Inducible Factors) in the adrenocortical cells of vertebrates is scant. By creating a unique set of transgenic mouse lines, we reveal a prominent role for HIF1alpha in the synthesis of virtually all steroids in vivo. Specifically, mice deficient in HIF1alpha in adrenocortical cells displayed enhanced levels of enzymes responsible for steroidogenesis and a cognate increase in circulatory steroid levels. These changes resulted in cytokine alterations and changes in the profile of circulatory mature hematopoietic cells. Conversely, HIF1alpha overexpression resulted in the opposite phenotype of insufficient steroid production due to impaired transcription of necessary enzymes. Based on these results, we propose HIF1alpha to be a vital regulator of steroidogenesis as its modulation in adrenocortical cells dramatically impacts hormone synthesis with systemic consequences. In addition, these mice can have potential clinical significances as they may serve as essential tools to understand the pathophysiology of hormone modulations in a number of diseases associated with metabolic syndrome, auto-immunity or even cancer. |
