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Horm Metab Res 2018; 50(02): 168-174
DOI: 10.1055/s-0043-120064
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

PreImplantation Factor (PIF*) Regulates Stress-Induced Adrenal Steroidogenesis and Anti-Inflammatory Cytokines: Potential Application for Bioartificial Adrenal Transplant

Autoren

  • Mariya Balyura   #

    1   Dept. of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

  • Evgeny Gelfgat   #

    1   Dept. of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

  • Enrico Ullmann

    1   Dept. of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    2   Department for Child and Adolescence Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany

  • Barbara Ludwig

    1   Dept. of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    3   Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden Faculty of Medicine, Technische Universität Dresden, DZD-German Centre for Diabetes Research, Dresden, Germany
    4   Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany

  • Eytan R. Barnea

    5   BioIncept LLC, New York, NY, USA
    6   SIEP, Society for the Investigation of Early Pregnancy, New York, NY, USA

  • Stefan R. Bornstein

    1   Dept. of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    3   Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden Faculty of Medicine, Technische Universität Dresden, DZD-German Centre for Diabetes Research, Dresden, Germany
    4   Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany
    7   Diabetes and Nutritional Sciences Division, King’s College London, London, UK
Weitere Informationen

Publikationsverlauf

received 21. Juni 2017

accepted 13. September 2017

Publikationsdatum:
24. Oktober 2017 (online)

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Abstract

The main treatment algorithm for adrenal insufficiency is hormonal replacement, however, inadequate hormone substitution often leads to severe side effects. Adrenal cell transplantation could be a more effective alternative but would require life-long immune suppressive therapy. PreImplantation Factor (PIF) is an endogenous peptide secreted by viable human embryos that leads to maternal tolerance without immunosuppression. PIF could be effective for xenogeneic cell transplantation such as of bovine adrenocortical cells (BAC), which are used for bioartificial adrenal gland development that may more effectively restore complex adrenal functions. We report here that PIF exerts a dual regulatory effect on BAC by targeting mostly hyper-activated cells to specifically reduce adrenocorticotropic hormone (ACTH)-stimulated cortisol secretion. Reverse transcription real time PCR analysis revealed that PIF modulates the expression of two genes in the cortisol synthesis pathway, Steroidogenic Factor 1 (SF1), an activator of steroidogenesis, and the downstream steroidogenic enzyme Cytochrome P450 17A1 (CYP17A1). PIF increased basal expression of SF1 and CYP17A1 regardless of the activation level of the adrenocortical cells. In contrast, following ACTH stimulation, PIF reduced SF1 expression and induced expression of the immune suppressing anti-inflammatory cytokine IL10 only in the hyper-activated cells, suggesting both a protective and immune tolerant function. In conclusion, PIF regulates stress-induced adrenal steroidogenesis and immune tolerance in BAC, supporting a potential clinical application to reduce rejection by the host’s immune response following xenotransplantation.

Key words

adrenocortical cells - immune tolerance - immune regulation

# Mariya Balyura and Evgeny Gelfgat contributed equally to this work


* Proprietary