title: Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development.
abstract: The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy, whereas in tumors establishing new blood supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis. In this review we focus on the well-established role of androgen regulation of angiogenesis in cancer and relate these mechanisms to placental angiogenesis. The physiological actions of androgens are mediated by the androgen receptor (AR), a ligand dependent transcription factor. Androgens and the AR are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further delineate the role of androgen signalling in placental function and maternal and offspring health in animal models.
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Health Sciences, University of Nottingham, LE12 5RD, UK.
authors.forename: Veronika M
authors.initials: VM
authors.lastname: Metzler
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Health Sciences, University of Nottingham, LE12 5RD, UK.
authors.forename: Simone
authors.initials: S
authors.lastname: de Brot
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Health Sciences, University of Nottingham, LE12 5RD, UK.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Robinson
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Health Sciences, University of Nottingham, LE12 5RD, UK.
authors.forename: Jennie N
authors.initials: JN
authors.lastname: Jeyapalan
authors.affiliation: School of Medicine and Sciences, University of Nottingham, Nottingham City Hospital, NG5 1PB, UK.
authors.forename: Emad
authors.initials: E
authors.lastname: Rakha
authors.affiliation: Department of Urology, Nottingham University Hospitals NHS Trust, NG5 1PB, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Walton
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Health Sciences, University of Nottingham, LE12 5RD, UK.
authors.forename: David S
authors.initials: DS
authors.lastname: Gardner
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Health Sciences, University of Nottingham, LE12 5RD, UK.
authors.forename: Emma F
authors.initials: EF
authors.lastname: Lund
authors.affiliation: School of Pharmacy, University of Nottingham, NG7 2TQ, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Whitchurch
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Health Sciences, University of Nottingham, LE12 5RD, UK.
authors.forename: Daisy
authors.initials: D
authors.lastname: Haigh
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Health Sciences, University of Nottingham, LE12 5RD, UK.
authors.forename: Jack M
authors.initials: JM
authors.lastname: Lochray
authors.affiliation: Department of Pathology, Weill Cornell Medicine, New York 10065, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robinson
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Health Sciences, University of Nottingham, LE12 5RD, UK.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Allegrucci
authors.affiliation: School of Biosciences, University of Nottingham, LE12 5RD, UK.
authors.forename: Rupert G
authors.initials: RG
authors.lastname: Fray
authors.affiliation: Department of Translational Medicine, Lund University, Malmö, Sweden; Department of Molecular Biology, Umeå University, Sweden.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Persson
authors.affiliation: Department of Immunology and Microbiology, University of Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Ødum
authors.affiliation: Department of Molecular Biology, Umeå University, Sweden; Kazan Federal University, Kazan, Republic of Tatarstan 420008, Russian Federation.
authors.forename: Regina R
authors.initials: RR
authors.lastname: Miftakhova
authors.affiliation: Kazan Federal University, Kazan, Republic of Tatarstan 420008, Russian Federation.
authors.forename: Albert A
authors.initials: AA
authors.lastname: Rizvanov
authors.affiliation: Department of Paediatrics, University of Cambridge, Hills Rd, Cambridge CB2 0QQ, UK.
authors.forename: Ieuan A
authors.initials: IA
authors.lastname: Hughes
authors.affiliation: Department of Paediatrics, University of Cambridge, Hills Rd, Cambridge CB2 0QQ, UK.
authors.forename: Rieko
authors.initials: R
authors.lastname: Tadokoro-Cuccaro
authors.affiliation: School of Pharmacy, University of Nottingham, NG7 2TQ, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Heery
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Health Sciences, University of Nottingham, LE12 5RD, UK. Electronic address: Catrin.rutland@nottingham.ac.uk.
authors.forename: Catrin S
authors.initials: CS
authors.lastname: Rutland
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Health Sciences, University of Nottingham, LE12 5RD, UK; Department of Pharmacology, Weill Cornell Medicine, New York 10065, USA. Electronic address: Nigel.mongan@nottingham.ac.uk.
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Mongan
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D005260:Female; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010929:Placentation / Q000502:physiology*; D011247:Pregnancy
chemical_list: D000728:Androgens
keywords: Angiogenesis; Epigenetics; Nuclear receptor; VEGF