Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

Toivanen, Roxanne; Shen, Michael M.

doi:10.1242/dev.148270

Cited by 146 publications

(141 citation statements)

References 226 publications

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“…Studies have shown that mediators secreted by macrophage may interact with Leydig cells as well as other cells present in testes, thereby causing the hypoandrogenism related to the arthritis (Clemens & Bruot, ; Bruot & Clemens, ; Bendele et al ., ). In this manner, this slight reduction in the prostate wet mass may be a consequence of an AIA‐induced hypoandrogenism because this gland is an androgen‐dependent organ (Toivanen & Shen, ).…”

Section: Discussionmentioning

confidence: 99%

“…Like the testes, the male sex glands can also be affected by RA, as they are androgen‐dependent organs. Actually, testosterone is essential for both the proliferation of the epithelium and the secretory activity of these glands (Toivanen & Shen, ; McKay & Sharma, ). Furthermore, it cannot be ruled out that inflammatory mediators from the injured joints can act directly on the male sex glands, regardless of hypoandrogenism secondary to arthritis.…”

Section: Introductionmentioning

confidence: 99%

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Adjuvant‐induced arthritis affects testes and ventral prostate of Wistar rats

et al. 2019

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Background Rheumatoid arthritis (RA) may reduce the testosterone production, thereby leading to testicular dysfunction and subfertility. Objectives This study aimed to evaluate whether adjuvant‐induced arthritis (AIA) induces histopathological and morphometric‐stereological alterations on testes with repercussions on the prostate, and alternatively, verifying AIA‐induced direct effects on the prostate, regardless of the testicular involvement. Material and methods Adult male Wistar rats were sham‐orchiectomized or orchiectomized. Twenty days after the surgery, these animals were injected with vehicle (SHAM and ORQ groups, respectively) or adjuvant (Mycobacterium tuberculosis) to induce arthritis (AIA and ORQ/AIA groups, respectively). Forty days later, testes and ventral prostate were processed for histopathological and morphometric‐stereological analyses, as well as to PCNA immunohistochemistry. Collagen deposit was evaluated in prostate. Circulating testosterone levels were determined 15 days post‐AIA induction in SHAM and AIA rats and 40th day in all groups. Results In the testes, AIA promoted histopathological changes characterized by an increase in the percentage of abnormal tubules and reduction in the height of the seminiferous epithelium, daily production of spermatozoa, and cellular proliferation. In the prostate, AIA decreased the luminal volume of the secretory ducts. In condition of androgenic deprivation due to the orchiectomy, AIA induced proliferation of the prostatic epithelium. Discussion The effects of arthritis on testes and prostate were observed 40 days post‐AIA induction, possibly results of the hypoandrogenism were already established on 15th day post‐induction, which is related to the decline of the steroidogenesis in the Leydig cells. On the other hand, the joint inflammatory process may also have direct repercussions upon the prostate, regardless of this hypoandrogenism. Conclusion AIA effects on reproductive tissues may be related to both hypoandrogenism and other direct inflammatory mechanisms. Possibly, these AIA effects on the testes and prostate occur at a stage in which the inflammatory process is most active, about 15–20 days after induction, remaining evident until the 40th day.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adjuvant‐induced arthritis affects testes and ventral prostate of Wistar rats

et al. 2019

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“…Mezodermal kökenli olan mezonefrik (Wolffian kanalı) ve paramezonefrik (Müller kanalı) kanalları, genitoüriner sistemin gelişmesinde görev alır. 10 Wolffian kanalının yapıları testosteron kontrolü ile oluşurken, ürogenital sinüs gelişimi DHT bağımlıdır. Tam prostat morfogenezi için, testosteronun 5α redüktaz ile hücre içi DHT'ye dönüştürülmesi gereklidir.…”

Section: Prostat Bezi̇unclassified

The Effects of Endocrine Disrupting Chemicals on Prostate Gland

Köse¹,

Erkekoğlu²,

Koçer-Gümüşel³

2020

J Lit Pharm Sci

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“…Its interaction with organ-specific hormone signals may be important for orchestrating the functions of adult stem cells in that tissue. In the prostate, both the canonical Wnt signaling and androgen signaling pathways have been shown to be essential in driving organogenesis (Toivanen and Shen, 2017). Specifically, stromal Wnt secretion promotes prostate bud branching morphogenesis and expression of the prostatespecific transcription factor Nkx3.1 in the epithelium (Francis et al, 2013;Julio et al, 2013;Simons et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Modulation of the canonical Wnt activity by androgen signaling in prostate epithelial basal stem cells

Liu

Wang

Horton

et al. 2020

Preprint

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Both the canonical Wnt signaling and androgen signaling are important factors regulating prostate organogenesis. How these two pathways crosstalk to regulate prostate stem cell functions remain unclear. Here, we show that while canonical Wnt activity is required for prostate basal stem cell multipotency in vivo, ectopic Wnt activity does not promote basal-to-luminal cell differentiation. We provide evidence that androgen signaling may keep Wnt activity in check. In prostate organoid culture from basal cells, dihydrotestosterone (DHT) antagonizes R-spondin-stimulated organoid growth in a concentration-dependent manner. Molecular analyses of organoids under different treatment conditions showed that androgen signaling downregulated the expressions of a Wnt reporter as well as many Wnt target genes.Pathway analysis and gene set enrichment analysis of organoid RNA-seq data also revealed the canonical Wnt signaling as a key pathway distinguishing organoids treated with or without DHT. Notably, DHT treatment enhanced AR and β-catenin binding in the nuclei of prostate organoids, providing possible mechanistic clues. Our results reveal a critical role of AR signaling in modulating canonical Wnt activity in prostate basal cells to regulate their multipotency.

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Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

Cited by 146 publications

References 226 publications

Adjuvant‐induced arthritis affects testes and ventral prostate of Wistar rats

Adjuvant‐induced arthritis affects testes and ventral prostate of Wistar rats

The Effects of Endocrine Disrupting Chemicals on Prostate Gland

Modulation of the canonical Wnt activity by androgen signaling in prostate epithelial basal stem cells

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