PMID- 29869453
OWN - NLM
STAT- MEDLINE
DCOM- 20191028
LR  - 20191028
IS  - 2047-2927 (Electronic)
IS  - 2047-2919 (Linking)
VI  - 6
IP  - 5
DP  - 2018 Sep
TI  - Insights into the role of androgen receptor in human testicular peritubular 
      cells.
PG  - 756-765
LID - 10.1111/andr.12509 [doi]
AB  - Contractile smooth muscle-like peritubular cells build the wall of seminiferous 
      tubules in men. They are crucial for sperm transport and complement the functions 
      of Sertoli cells by secreting factors, including glial cell line-derived 
      neurotrophic factor. Previous studies revealed that they also secrete the 
      chemokine C-X-C motif chemokine ligand 12 (CXCL12), which has known roles in 
      spermatogenesis. Peritubular cells express the androgen receptor (AR), which is 
      retained in isolated human testicular peritubular cells. We aimed to explore 
      AR-regulated functions in human testicular peritubular cells. Bearing in mind 
      that infertile men often have high aromatase activity, which may lower 
      intratesticular androgen concentrations, an animal model for male infertility was 
      studied. These mice display an age-dependent loss in spermatogenesis due to high 
      aromatase activity. Human testicular peritubular cells were exposed to 
      dihydrotestosterone or the antiandrogen flutamide. We studied AR, smooth muscle 
      cell markers, glial cell line-derived neurotrophic factor and 15 secreted factors 
      previously identified, including CXCL12. We used qPCR, Western blotting, ELISA or 
      selected reaction monitoring (SRM). In the animal model for male infertility, we 
      employed qPCR and immunohistochemistry. Dihydrotestosterone increased AR and 
      flutamide prevented these actions. The smooth muscle cell markers calponin and 
      smooth muscle actin were likewise increased, while cell size or cellular 
      proliferation was not changed. Dihydrotestosterone did not increase glial cell 
      line-derived neurotrophic factor or CXCL12 secretion but increased levels of 
      serine proteinase inhibitor (SERPIN) E1. The animal model for male infertility 
      with high aromatase activity showed reduced numbers of AR-immunoreactive 
      testicular peritubular cells, suggesting that altered androgen and/or oestrogen 
      levels could influence AR-mediated responses in peritubular cells. Androgens act 
      on human testicular peritubular cells to enhance AR levels, their contractile 
      phenotype and to modulate the secretion of some secreted factors. This study 
      suggests that some aspects of human peritubular cell functions are regulated by 
      androgens.
CI  - (c) 2018 American Society of Andrology and European Academy of Andrology.
FAU - Mayer, C
AU  - Mayer C
AD  - Cell Biology, Anatomy III, BMC Munich, Ludwig-Maximilians-Universitat (LMU), 
      Munich, Germany.
FAU - Adam, M
AU  - Adam M
AD  - Cell Biology, Anatomy III, BMC Munich, Ludwig-Maximilians-Universitat (LMU), 
      Munich, Germany.
AD  - Turku Center for Disease Modeling and Institute of Biomedicine, University of 
      Turku, Turku, Finland.
FAU - Walenta, L
AU  - Walenta L
AD  - Cell Biology, Anatomy III, BMC Munich, Ludwig-Maximilians-Universitat (LMU), 
      Munich, Germany.
FAU - Schmid, N
AU  - Schmid N
AD  - Cell Biology, Anatomy III, BMC Munich, Ludwig-Maximilians-Universitat (LMU), 
      Munich, Germany.
FAU - Heikela, H
AU  - Heikela H
AD  - Turku Center for Disease Modeling and Institute of Biomedicine, University of 
      Turku, Turku, Finland.
FAU - Schubert, K
AU  - Schubert K
AD  - Cell Biology, Anatomy III, BMC Munich, Ludwig-Maximilians-Universitat (LMU), 
      Munich, Germany.
FAU - Flenkenthaler, F
AU  - Flenkenthaler F
AD  - Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU, Munich, 
      Germany.
FAU - Dietrich, K-G
AU  - Dietrich KG
AD  - Cell Biology, Anatomy III, BMC Munich, Ludwig-Maximilians-Universitat (LMU), 
      Munich, Germany.
FAU - Gruschka, S
AU  - Gruschka S
AD  - Cell Biology, Anatomy III, BMC Munich, Ludwig-Maximilians-Universitat (LMU), 
      Munich, Germany.
FAU - Arnold, G J
AU  - Arnold GJ
AD  - Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU, Munich, 
      Germany.
FAU - Frohlich, T
AU  - Frohlich T
AD  - Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU, Munich, 
      Germany.
FAU - Schwarzer, J U
AU  - Schwarzer JU
AD  - Andrology-Center, Munich, Germany.
FAU - Kohn, F M
AU  - Kohn FM
AD  - Andrologicum, Munich, Germany.
FAU - Strauss, L
AU  - Strauss L
AD  - Turku Center for Disease Modeling and Institute of Biomedicine, University of 
      Turku, Turku, Finland.
FAU - Welter, H
AU  - Welter H
AD  - Cell Biology, Anatomy III, BMC Munich, Ludwig-Maximilians-Universitat (LMU), 
      Munich, Germany.
FAU - Poutanen, M
AU  - Poutanen M
AD  - Turku Center for Disease Modeling and Institute of Biomedicine, University of 
      Turku, Turku, Finland.
FAU - Mayerhofer, A
AU  - Mayerhofer A
AUID- ORCID: 0000-0002-9388-4639
AD  - Cell Biology, Anatomy III, BMC Munich, Ludwig-Maximilians-Universitat (LMU), 
      Munich, Germany.
LA  - eng
GR  - MA 1080/21-1/Deutsche Forschungsgemeinschaft (DFG)/International
GR  - MA 1080/23-1/Deutsche Forschungsgemeinschaft (DFG)/International
GR  - MA 1080/27-1/Deutsche Forschungsgemeinschaft (DFG)/International
GR  - Post-doc programme of the German Academic Exchange Service/International
GR  - 57347353/DAAD/International
GR  - Academy of Finland/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180605
PL  - England
TA  - Andrology
JT  - Andrology
JID - 101585129
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (GDNF protein, human)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Receptors, Androgen)
RN  - EC 1.14.14.1 (Aromatase)
SB  - IM
MH  - Animals
MH  - Aromatase/metabolism
MH  - Cells, Cultured
MH  - Chemokine CXCL12/metabolism
MH  - Disease Models, Animal
MH  - Glial Cell Line-Derived Neurotrophic Factor/metabolism
MH  - Humans
MH  - Infertility, Male/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptors, Androgen/metabolism/*physiology
MH  - Seminiferous Tubules/metabolism/*physiology
OTO - NOTNLM
OT  - infertility
OT  - smooth muscle cells
OT  - testis
OT  - testosterone
EDAT- 2018/06/06 06:00
MHDA- 2019/10/29 06:00
CRDT- 2018/06/06 06:00
PHST- 2017/10/27 00:00 [received]
PHST- 2018/05/08 00:00 [revised]
PHST- 2018/05/09 00:00 [accepted]
PHST- 2018/06/06 06:00 [pubmed]
PHST- 2019/10/29 06:00 [medline]
PHST- 2018/06/06 06:00 [entrez]
AID - 10.1111/andr.12509 [doi]
PST - ppublish
SO  - Andrology. 2018 Sep;6(5):756-765. doi: 10.1111/andr.12509. Epub 2018 Jun 5.