Activation of the HIF pathway in polycystic ovary syndrome (PCOS): hemoglobin, ferritin and HIF-targeted medical interventions
Thesis event information
Date and time of the thesis defence
Place of the thesis defence
University of Oulu, Aapistie 7A, Lecture hall K101
Topic of the dissertation
Activation of the HIF pathway in polycystic ovary syndrome (PCOS): hemoglobin, ferritin and HIF-targeted medical interventions
Doctoral candidate
Master of Science Nikke Virtanen
Faculty and unit
University of Oulu Graduate School, Faculty of Medicine, Research Unit of Clinical Medicine
Subject of study
Medicine
Opponent
Professor Colin Duncan, University of Edinburgh
Custos
Professor Terhi Piltonen, University of Oulu
Activation of the HIF pathway in polycystic ovary syndrome (PCOS)
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women, affecting one in eight women worldwide. The defining traits of the syndrome are excessive androgen levels, oligo- or amenorrhea, and polycystic ovarian morphology. Additionally, the disorder is commonly accompanied by severe comorbidities, such as obesity and insulin resistance. The disorder is also hereditary. Since there is currently no cure for PCOS, the primary mode of treatment is lifestyle modification and management of symptoms using various types of medication.
Hypoxia-inducible factor (HIF) is the central regulator of the cellular hypoxia response. In animal experiments, activation of the HIF signaling pathway has been shown to result in weight loss and restored glucose and insulin metabolism. Therapeutic agents based on the pharmacological induction of HIF activation have also been developed and are being used in the treatment of renal anemia.
The studies presented in this thesis investigated the potential role of HIF pathway activation in the metabolism of women with PCOS and in ameliorating the metabolic defects of PCOS. Using data from the Northern Finland Birth Cohort 1966, strong associations were discovered between higher hemoglobin (Hb) levels and a worse metabolic profile. Considering Hb as a proxy for tissue hypoxia, this provided further evidence for the significance of HIF in metabolism. When similar associations were investigated between ferritin levels and metabolism in women with PCOS, using data from the Women’s Health Study WENDY cohort, none of similar strength were found despite the higher ferritin levels in women with PCOS than those without PCOS. In the final study of this thesis, the effects of pharmacological HIF pathway activation on metabolism were investigated using a pre-clinical mouse model of PCOS. Significant weight independent alleviation of impaired glucose and insulin metabolism was detected in the group undergoing pharmacological HIF-activation.
The studies presented in this thesis provide insight into the significance of oxygen metabolism in PCOS and demonstrate the effectiveness of HIF activation in countering metabolic defects born of androgen excess.
Hypoxia-inducible factor (HIF) is the central regulator of the cellular hypoxia response. In animal experiments, activation of the HIF signaling pathway has been shown to result in weight loss and restored glucose and insulin metabolism. Therapeutic agents based on the pharmacological induction of HIF activation have also been developed and are being used in the treatment of renal anemia.
The studies presented in this thesis investigated the potential role of HIF pathway activation in the metabolism of women with PCOS and in ameliorating the metabolic defects of PCOS. Using data from the Northern Finland Birth Cohort 1966, strong associations were discovered between higher hemoglobin (Hb) levels and a worse metabolic profile. Considering Hb as a proxy for tissue hypoxia, this provided further evidence for the significance of HIF in metabolism. When similar associations were investigated between ferritin levels and metabolism in women with PCOS, using data from the Women’s Health Study WENDY cohort, none of similar strength were found despite the higher ferritin levels in women with PCOS than those without PCOS. In the final study of this thesis, the effects of pharmacological HIF pathway activation on metabolism were investigated using a pre-clinical mouse model of PCOS. Significant weight independent alleviation of impaired glucose and insulin metabolism was detected in the group undergoing pharmacological HIF-activation.
The studies presented in this thesis provide insight into the significance of oxygen metabolism in PCOS and demonstrate the effectiveness of HIF activation in countering metabolic defects born of androgen excess.
Last updated: 7.4.2025