Insights into the role of androgen receptor in human testicular peritubular cells

Mayer, Christine; Adam, Marion; Walenta, Lena; Schmid, Nina; Heikelä, Hanna; Schubert, Kerstin; Flenkenthaler, Florian; Dietrich, Kim-Gwendolyn; Gruschka, S.; Arnold, Georg J.; Fröhlich, Thomas; Schwarzer, Julia; Köhn, Frank-Michael; Strauss, Leena; Welter, Harald; Poutanen, Matti; Mayerhofer, Artur

doi:10.1111/andr.12509

Cited by 19 publications

(19 citation statements)

References 56 publications

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“…AR was not significantly altered in advanced passages. AR-activation enhances the smooth muscle-phenotype and thereby may regulate contractility of HTPCs 16 . In full accordance with the proteomic data, the smooth muscle factors ACTA2 and CNN1 also remained stable, thus HTPCs keep their smooth muscle-like phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…HTPCs produce important growth factor molecules, e.g. glial cell line derived factor (GDNF) and C-X-C motif chemokine ligand 12 (CXCL12) and thereby most likely contribute to the spermatogonial stem cell (SSC) niche of the testis and to life-long spermatogenesis 14–16 . Initially, Sertoli cells were known as sole producers of GDNF and an overall important part of the SSC niche.…”

Section: Introductionmentioning

confidence: 99%

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Insights into replicative senescence of human testicular peritubular cells

Schmid

Flenkenthaler²,

Stöckl³

et al. 2019

Sci Rep

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There is evidence for an age-related decline in male reproductive functions, yet how the human testis may age is not understood. Human testicular peritubular cells (HTPCs) transport sperm, contribute to the spermatogonial stem cell (SSC) niche and immune surveillance, and can be isolated and studied in vitro. Consequences of replicative senescence of HTPCs were evaluated to gain partial insights into human testicular aging. To this end, early and advanced HTPC passages, in which replicative senescence was indicated by increased cell size, altered nuclear morphology, enhanced β-galactosidase activity, telomere attrition and reduced mitochondrial DNA (mtDNA), were compared. These alterations are typical for senescent cells, in general. To examine HTPC-specific changes, focused ion beam scanning electron microscopy (FIB/SEM) tomography was employed, which revealed a reduced mitochondrial network and an increased lysosome population. The results coincide with the data of a parallel proteomic analysis and indicate deranged proteostasis. The mRNA levels of typical contractility markers and growth factors, important for the SSC niche, were not significantly altered. A secretome analysis identified, however, elevated levels of macrophage migration inhibitory factor (MIF) and dipeptidyl peptidase 4 (DPP4), which may play a role in spermatogenesis. Testicular DPP4 may further represent a possible drug target.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insights into replicative senescence of human testicular peritubular cells

Schmid

Flenkenthaler²,

Stöckl³

et al. 2019

Sci Rep

Self Cite

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“…Peritubular cells possess androgen receptors, yet expression levels of TRPV2 in these cells was not affected by DHT, a potent androgen, added to the culture medium for up to 7days. Such a treatment led to an increased expression of a growth factor ( PEDF ) in HTPCs [ 29 ], as well as smooth muscle markers and androgen receptors [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Ca2+ Signaling and IL-8 Secretion in Human Testicular Peritubular Cells Involve the Cation Channel TRPV2

Eubler¹,

Herrmann²,

Tiefenbacher³

et al. 2018

IJMS

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Peritubular cells are part of the wall of seminiferous tubules in the human testis and their contractile abilities are important for sperm transport. In addition, they have immunological roles. A proteomic analysis of isolated human testicular peritubular cells (HTPCs) revealed expression of the transient receptor potential channel subfamily V member 2 (TRPV2). This cation channel is linked to mechano-sensation and to immunological processes and inflammation in other organs. We verified expression of TRPV2 in peritubular cells in human sections by immunohistochemistry. It was also found in other testicular cells, including Sertoli cells and interstitial cells. In cultured HTPCs, application of cannabidiol (CBD), a known TRPV2 agonist, acutely induced a transient increase in intracellular Ca2+ levels. These Ca2+ transients could be blocked both by ruthenium red, an unspecific Ca2+ channel blocker, and tranilast (TRA), an antagonist of TRPV2, and were also abolished when extracellular Ca2+ was removed. Taken together this indicates functional TRPV2 channels in peritubular cells. When applied for 24 to 48 h, CBD induced expression of proinflammatory factors. In particular, mRNA and secreted protein levels of the proinflammatory chemokine interleukin-8 (IL-8/CXCL8) were elevated. Via its known roles as a major mediator of the inflammatory response and as an angiogenic factor, this chemokine may play a role in testicular physiology and pathology.

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“…In healthy prostatic epithelium tissue, AR, as a transcription factor, plays an essential role in regulating terminal differentiation, suppression of apoptosis, and hormone secretion [30]. The activation of AR by binding to androgens is associated with sexual reproduction and pubertal changes while maintaining libido and spermatogenesis levels in adult males [31,32,33,34,35,36]. AR in healthy prostate epithelium tissue regularly controls cell proliferation and programmed cell death; however, the loss of this control mechanism is observed in prostate cancer cells, and the molecular mechanisms remain unclear [31].…”

Section: The Androgen Receptor and Prostate Cancermentioning

confidence: 99%

Future Aspects of CDK5 in Prostate Cancer: From Pathogenesis to Therapeutic Implications

Oner

Lin

Chen

et al. 2019

IJMS

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Cyclin-dependent kinase 5 (CDK5) is a unique member of the cyclin-dependent kinase family. CDK5 is activated by binding with its regulatory proteins, mainly p35, and its activation is essential in the development of the central nervous system (CNS) and neurodegeneration. Recently, it has been reported that CDK5 plays important roles in regulating various biological and pathological processes, including cancer progression. Concerning prostate cancer, the androgen receptor (AR) is majorly involved in tumorigenesis, while CDK5 can phosphorylate AR and promotes the proliferation of prostate cancer cells. Clinical evidence has also shown that the level of CDK5 is associated with the progression of prostate cancer. Interestingly, inhibition of CDK5 prevents prostate cancer cell growth, while drug-triggered CDK5 hyperactivation leads to apoptosis. The blocking of CDK5 activity by its small interfering RNAs (siRNA) or Roscovitine, a pan-CDK inhibitor, reduces the cellular AR protein level and triggers the death of prostate cancer cells. Thus, CDK5 plays a crucial role in the growth of prostate cancer cells, and AR regulation is one of the important pathways. In this review paper, we summarize the significant studies on CDK5-mediated regulation of prostate cancer cells. We propose that the CDK5–p35 complex might be an outstanding candidate as a diagnostic marker and potential target for prostate cancer treatment in the near future.

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Insights into the role of androgen receptor in human testicular peritubular cells

Cited by 19 publications

References 56 publications

Insights into replicative senescence of human testicular peritubular cells

Insights into replicative senescence of human testicular peritubular cells

Ca2+ Signaling and IL-8 Secretion in Human Testicular Peritubular Cells Involve the Cation Channel TRPV2

Future Aspects of CDK5 in Prostate Cancer: From Pathogenesis to Therapeutic Implications

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