HIF1α is a direct regulator of steroidogenesis in the adrenal gland

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 HIF1α in the synthesis of virtually all steroids in vivo. Specifically, mice deficient in HIF1α 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, HIF1α overexpression resulted in the opposite phenotype of insufficient steroid production due to impaired transcription of necessary enzymes. Based on these results, we propose HIF1α 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.

Gestagens in assisted reproductive technology programs

Background. Luteal phase (LP) drug support is an important step in assisted reproductive technology (ART) programs efficacy. Aim. To present up-to-date data on an efficacy of LP hormonal support during ART cycles as well as to conduct a comparative analysis of various gestagen drug effectiveness. Materials and methods. To write this review domestic and foreign publications were searched in Russian and international search systems (PubMed, eLibrary, etc.) for the last 8 years. The review includs articles from peer-reviewed literature. Results. LP drug support becomes an essential step in infertility treatment in various ART programs. Although human chorionic gonadotropin drug injections in the posttransfer period leads to an activation of endogenous steroid hormones synthesis, exogenous hormones use is currently preferred because of not having a risk of ovarian hyperstimulation syndrome. Conclusions. The variety of progesterone drugs is accompanied by a lack of algorithms for their use in various clinical situations. Further studies are required to evaluate progesterone drugs efficacy for various subgroups of patients.