Inhibin-related proteins in rat prostate

Risbridger, Gail P.; Thomas, Tania Z.; Gurusinghe, Chandan J.; McFarlane, James R.

doi:10.1677/joe.0.1490093

Cited by 30 publications

(12 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1B and 2). Previous studies have shown that the activin/follistatin system, which is present in the prostate tissue, plays a crucial role in the local regulation of human prostate cell growth (20,28). In addition, our results suggest that activin and follistatin also play an important role in the regulation of PSA production and secretion by the prostatic cells.…”

Section: Discussionsupporting

confidence: 72%

“…Activins are dimeric proteins composed of two inhibin-␤ proteins translated from at least five different gene transcripts, referred to as ␤A, ␤B, ␤C, ␤D, and ␤E. Activins are multifunctional growth and differentiation factors participating in the regulation of many biological systems and processes, including embryonic development, erythroid differentiation, and tumorigenesis (14,17,21,22), by interactions with specific cell surface receptors that show considerable subtype diversity (12) and have been identified in many tissues (10), including the prostate (4,20,28) and prostate cancer cells (23). Activin A (the inhibin-␤A dimer) and activin B (the inhibin-␤B dimer) have profound effects on cell growth and function.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Regulation of prostate-specific antigen by activin A in prostate cancer LNCaP cells

Fujii¹,

Kawakami²,

Okada³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Activins are multifunctional growth and differentiation factors and stimulate FSH-β gene expression and FSH secretion by the pituitary gonadotropes. Follistatins bind activin, resulting in the neutralization of activin bioactivity. The activin/follistatin system is present in the prostate tissue. Prostate-specific antigen (PSA) plays an important role in male reproductive physiology as well as being very important as a tumor marker for prostate cancer. Thus the regulation of PSA has important clinical implications. Previous studies showed that PSA is primarily regulated by androgens. In the present study, we evaluated the direct effects of activin A on the proliferation and PSA production of prostate cancer LNCaP cells, which express functional activin receptors and androgen receptor and PSA. LNCaP cells were treated with activin A and 5α-dihydrotestosterone (DHT) with or without their antagonists (follistatin or the nonsteroidal anti-androgen bicalutamide). Activin A decreased cell growth of LNCaP cells in a dose-dependent manner, whereas DHT increased it in a biphasic manner. In contrast to their opposing actions on cell growth, both activin A and DHT upregulated PSA gene expression and increased PSA secretion by LNCaP cells. The effects of activin A and DHT to increase PSA production were synergistic or additive. Follistatin or bicalutamide was without effect on cell growth or PSA production. The effects of activin A on LNCaP cells were blocked by follistatin, not by bicalutamide, whereas effects of DHT were prevented by bicalutamide, not by follistatin. Activin A upregulates PSA production, and the effect is through an androgen receptor-independent pathway. The activin/follistatin system can be a physiological modulator of PSA gene transcription and secretion in the prostate tissue, and activins may cooperate with androgen to upregulate PSA in vivo.

show abstract

Section: Discussionsupporting

confidence: 72%

mentioning

confidence: 99%

Regulation of prostate-specific antigen by activin A in prostate cancer LNCaP cells

Fujii¹,

Kawakami²,

Okada³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…In the Wolffian duct, initial expression of mesenchymal activin A is androgen independent, but expression at later developmental stages requires testosterone (16). Androgens are similarly known to positively influence activin A levels in the adult prostate, although it is unclear whether androgens also regulate activin A production during prostate development (35). The possibility of a similar relationship between androgens and activin A expression in the fetal testes certainly warrants further investigation.…”

Section: Discussion Fetal Leydig Cells Actively Promote Sertoli Cell mentioning

confidence: 99%

Activin A, a product of fetal Leydig cells, is a unique paracrine regulator of Sertoli cell proliferation and fetal testis cord expansion

Archambeault

Yao

2010

Proc. Natl. Acad. Sci. U.S.A.

122

112

View full text Add to dashboard Cite

Formation of tubular structures relies upon complex interactions between adjacent epithelium and mesenchyme. In the embryonic testes, dramatic compartmentalization leads to the formation of testis cords (epithelium) and the surrounding interstitium (mesenchyme). Sertoli cells, the epithelial cell type within testis cords, produce signaling molecules to orchestrate testis cord formation. The interstitial fetal Leydig cells, however, are thought only to masculinize the embryo and are not known to be involved in testis cord morphogenesis. Contrary to this notion, we have identified activin A, a member of the TGF-β protein superfamily, as a product of the murine fetal Leydig cells that acts directly upon Sertoli cells to promote their proliferation during late embryogenesis. Genetic disruption of activin βA, the gene encoding activin A, specifically in fetal Leydig cells resulted in a failure of fetal testis cord elongation and expansion due to decreased Sertoli cell proliferation. Conditional inactivation of Smad4 , the central component of TGF-β signaling, in Sertoli cells led to testis cord dysgenesis and proliferative defects similar to those of Leydig cell-specific activin βA knockout testes. These results indicate that activin A is the major TGF-β protein that acts directly on Sertoli cells. Testicular dysgenesis in activin βA and Smad4 conditional knockout embryos persists into adulthood, leading to low sperm production and abnormal testicular histology. Our findings challenge the paradigm that fetal testis development is solely under the control of Sertoli cells, by uncovering an active and essential role of fetal Leydig cells during testis cord morphogenesis.

show abstract

“…TGF-␤ receptors, however, are frequently lost in prostate cancer cells, which consequently acquire resistance to the apoptotic effect of TGF-␤ (40). BMP-2 receptors and activin and inhibin are also present in prostate tissue (41,42). Prostate tumors express significantly lower levels of activin receptor 1B mRNA when compared with nonmalignant tissue (43).…”

Section: Discussionmentioning

confidence: 99%

Mullerian-inhibiting substance regulates NF–κB signaling in the prostatein vitroandin vivo

Segev

Hoshiya

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Mullerian-inhibiting substance (MIS) is a member of the transforming growth factor ␤ superfamily, a class of molecules that regulates growth, differentiation, and apoptosis in many cells. MIS type II receptor in the Mullerian duct is temporally and spatially regulated during development and becomes restricted to the most caudal ends that fuse to form the prostatic utricle. In this article, we have demonstrated MIS type II receptor expression in the normal prostate, human prostate cancer cell lines, and tissue derived from patients with prostate adenocarcinomas. MIS induced NF-B DNA binding activity and selectively up-regulated the immediate early gene IEX-1S in both androgen-dependent and independent human prostate cancer cells in vitro. Dominant negative IB␣ expression ablated both MIS-induced increase of IEX-1S mRNA and inhibition of growth, indicating that activation of NF-B signaling was required for these processes. Androgen also induced NF-B DNA binding activity in prostate cancer cells but without induction of IEX-1S mRNA, suggesting that MIS-mediated increase in IEX-1S was independent of androgen-mediated signaling. Administration of MIS to male mice induced IEX-1S mRNA in the prostate in vivo, suggesting that MIS may function as an endogenous hormonal regulator of NF-B signaling and growth in the prostate gland. IEX-1M ullerian-inhibiting substance (MIS) belongs to the transforming growth factor ␤ (TGF-␤) superfamily, which also includes activins, inhibins, and the bone morphogenetic proteins. The Mullerian duct, the anlagen of the uterus, Fallopian tubes, and upper vagina in the female, regresses in the presence of MIS in male embryos (1). The MIS type II receptor, a transmembrane serine threonine kinase, is expressed at high levels in the Mullerian duct and in the embryonic and adult gonads (2). Lower levels of receptor expression were detected in the mammary gland and embryonic rat lungs (3-5), which show functional responses to MIS.The binding of MIS to its receptor initiates a signaling cascade that depends on the recruitment of type I receptors ALK2 and ALK6 (6-8). We recently demonstrated that MIS inhibited the growth of breast cancer cells in vitro through induction of NF-B (4), a family of transcription factors that includes p50, p65, p52, and c-rel. These transactivators form either homodimers or heterodimers that are retained in the cytoplasm by a class of inhibitor proteins, IB-␣, IB-␤, IB-␥, and IB-. Nuclear translocation of NF-B after phosphorylation and degradation of IB results in changes in gene expression (9, 10). MIS selectively up-regulated the immediate early gene IEX-1S through an NF-B-dependent mechanism in breast cancer cells, and IEX-1S, when overexpressed in these cells, inhibited growth (4), indicating a negative growth regulatory role for this newly identified NF-B-inducible gene.MIS type II receptor expression in the Mullerian duct is temporally and spatially regulated in the male embryo (11). Receptor expression is initially highest at the cranial end and gradually shifts t...

show abstract

Inhibin-related proteins in rat prostate

Cited by 30 publications

References 14 publications

Regulation of prostate-specific antigen by activin A in prostate cancer LNCaP cells

Regulation of prostate-specific antigen by activin A in prostate cancer LNCaP cells

Activin A, a product of fetal Leydig cells, is a unique paracrine regulator of Sertoli cell proliferation and fetal testis cord expansion

Mullerian-inhibiting substance regulates NF–κB signaling in the prostatein vitroandin vivo

Contact Info

Product

Resources

About