Mechanisms of Steroid Hormone Action

​Description of Research

In a traditional view, the endocrine action of steroid hormones is based on the concept where the hormone is synthesized in the gland and reaches the target organ via blood circulation. Our group has been actively involved in studies providing evidence for the concept of “intracrinology”, where the ligand concentration available for nuclear receptor is regulated also by the target tissue metabolism. Especially, we study the role of HSD17B enzymes in the steroid and lipid metabolism by applying genetically modified mouse models, tumor xenografts and by using clinical specimens. Current topics include: 1) To define the role of HSD17B enzymes in regulating the amount and type of ligand for nuclear receptor action, 2) To define the role of local sex steroid synthesis in the etiopathogenesis of breast and prostate cancer, and 3) To define the role of intra tissue sex steroid synthesis and steroid hormone action in endometrium and the role of the enzymes in etiopathogenesis of endometriosis. Of the research techniques we have devoted to efficient production of various genetically modified mouse models, to generate novel statistical methods for studies in vivo, and to set-up novel methods for steroid analyses using mass spectrometric methods.

Members of the research group

Senior Scientists/Post Docs:

Pirjo Pakarinen, PhD, Adjunct Professor
Niina Saarinen-Aaltonen, PhD, Adjunct Professor
Leena Strauss, PhD, Adjunct Professor
Petra Sipilä, PhD, Adjunct Professor
Fuping Zhang, MD, PhD, Adjunct Professor
Taija Saloniemi-Heinonen, PhD
Jenni Mäki-Jouppila, PhD
Prem Adhikari, PhD

PhD Students:

Michael Gabriel, MD
Janne Hakkarainen, MSc
Marianne Hallamaa, MD
Hanna Heikelä, MSc
Heli Jokela, MSc
Päivi Järvensivu, MSc
Heidi Kemiläinen, MD
Matias Knuuttila, MSc
Daniel Laajala, MSc
Pia Suvitie, MD
Anni Vehmas, MSc

Selected Publications

Hakkarainen J, Jokela H, Pakarinen P, Heikelä H, Kätkänaho L, Vandenput L, Ohlsson C, Zhang FP,  Poutanen M. Hydroxysteroid (17β)-dehydrogenase 1-deficient female mice present with normal puberty onset but are severely subfertile due to a defect in luteinization and progesterone production. FASEB J. 2015 Sep;29(9):3806-16.

Huhtinen K, Saloniemi-Heinonen T, Keski-Rahkonen P, Desai R, Laajala D, Ståhle M, Häkkinen MR, Awosanya M, Suvitie P, Kujari H, Aittokallio T, Handelsman DJ, Auriola S, Perheentupa A, Poutanen M. Intra-tissue steroid profiling indicates differential progesterone and testosterone metabolism in the endometrium and endometriosis lesions. J Clin Endocrinol Metab. 2014 Nov;99(11):E2188-97.

Knuuttila M, Yatkin E, Kallio J, Savolainen S, Laajala TD, Aittokallio T, Oksala R, Häkkinen M, Keski-Rahkonen P, Auriola S, Poutanen M, Mäkelä S. Castration induces up-regulation of intratumoral and-rogen biosynthesis and androgen receptor expression in an orthotopic VCaP human prostate cancer xenograft model. Am J Pathol. 2014 Aug;184(8):2163-73.

Strauss L, Rantakari P, Sjögren K, Salminen A, Lauren E, Kallio J, Damdimopoulou P, Boström M, Bos-tröm PJ, Pakarinen P, Zhang F, Kujala P, Ohlsson C, Mäkelä S, Poutanen M. Seminal vesicles and urinary bladder as sites of aromatization of androgens in men, evidenced by a CYP19A1-driven luciferase reporter mouse and human tissue specimens. FASEB J. 2013 Apr;27(4):1342-50

Laajala TD, Corander J, Saarinen NM, Mäkelä K, Savolainen S, Suominen MI, Alhoniemi E, Mäkelä S, Poutanen M, Aittokallio T. Improved statistical modeling of tumor growth and treatment effect in preclinical animal studies with highly heterogeneous responses in vivo. Clin Cancer Res. 2012 Aug 15;18(16):4385-96.