Androgen regulation of male reproductive health
Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku
Arttu Junnila, MSc
The goal of the project
Androgens are required for the male reproductive tissues. In addition, androgens regulate gene ex-pression in several non-reproductive tissues. Defects in androgen signaling are linked to diseases, such as prostate cancer. Androgens act through androgen receptor, AR, a hormone-inducible nuclear receptor. Upon ligand binding, AR is shuttled to the nucleus where it binds to the androgen response elements to regulate gene transcription. Specificity of spatiotemporal androgen regulation in different tissues is achieved by differential usage of coregulators. However, in many target tissues the regulation of cell type specific responses to androgen action remain poorly understood. Given the importance of androgen action, it is necessary to understand how androgen actions are normally regulated. We are especially interested in how tissue-specific androgen responses are mediated via pioneer factors, collaborating transcription factors and small RNAs, namely microRNAs in the male reproductive tissues.
Zhang F-P, Malinen M, Mehmood A, Lehtiniemi T, Jääskeläinen T, Korhonen H, Laiho A, Elo L, Ohlsson C, Kotaja N, Poutanen M, Sipilä P*, Palvimo J.* Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction. Nature Communications 2019 Feb 15;10(1):777, * equal contribution
Wu J, Movérare-Skrtic S, Zhang FP, Koskela A, Tuukkanen J, Palvimo JJ, Sipilä P, Poutanen M, Ohlsson C. Androgen receptor SUMOylation regulates bone mass in male mice. Mol Cell Endocrinol. 2018 Sep 24. pii: S0303-7207(18)30278-8
Huhtaniemi R, Oksala R, Knuuttila M, Mehmood A, Aho E, Laajala TD, Aittokallio T, Laiho A, Elo L, Ohlsson C, Kallio P, Mäkelä S, Mustonen MVJ, Sipilä P, Poutanen M. Adrenals contribute to growth of castration-resistant VCaP prostate cancer xenografts. Am J Pathol. 2018 Dec;188(12):2890-2901.
Knuuttila M, Mehmood A, Mäki-Jouppila J, Ryberg H, Taimen P, Knaapila J, Ettala O, Boström PJ, Ohlsson C, Venäläinen MS, Laiho A, Elo LL, Sipilä P, Mäkelä SI, Poutanen M. Intratumoral androgen levels are linked to TMPRSS2-ERG fusion in prostate cancer. Endocrine-Related Cancer 2018 25:807-819.
Hakkarainen J, Zhang F-P, Cisneros Montalvo S, Nurmio M, Toppari J, Ohlsson C, Kotaja N, Sipilä P, Poutanen M. Hydroxysteroid (17β) dehydrogenase 1 expressed by Sertoli cells contributes to steroid synthesis and is required for male fertility. FASEB J Jan 24:fj201700921R. doi: 10.1096/fj.201700921R
Knuuttila M, Mehmood A, Huhtaniemi R, Häkkinen MR, Oksala R, Laajala TD, Ryberg H, Handelsman DJ, Aittokallio T, Auriola S, Ohlsson C, Laiho A, Elo LL, Sipilä P, Mäkelä SI, Poutanen M. Antiandrogens reduce intratumoral androgen concentrations and induce androgen receptor expression in castration-resistant prostate cancer xenografts. Am J Pathol. 2018 Jan;188(1):216-228.
Björkgren I, Alvarez L, Blank N, Balbach M, Turunen H, Laajala TD, Toivanen J, Krutskikh A, Wahlberg N, Huhtaniemi I, Poutanen M, Wachten D, Sipilä P. Targeted inactivation of the mouse epididymal beta-defensin 41 alters sperm flagellar beat pattern and zona pellucida binding. Mol Cell Endocrinol. 2016 May 15;427:143-54.
Björkgren I, Gylling H, Turunen H, Huhtaniemi I, Strauss L, Poutanen M and Sipilä P. Imbalanced lipid homeostasis in the conditional Dicer1 knock-out mouse epididymis causes instability of the sperm membrane. FASEB J, 2014 29:433-42
Björkgren I, Saastamoinen L, Krutskikh A, Huhtaniemi I, Poutanen M and Sipilä P. Dicer1 ablation in the mouse epididymis causes dedifferentiation of the epithelium and imbalance in sex steroid signaling. PLoS One, 2012 7(6):e38457
Petra Sipilä, PhD
Adjunct Professor of Reproductive and Developmental Biology