Analysis of the mRNA expression of the <i>TGF‐Beta</i> family in testicular cells and localization of the splice variant TGF‐β2B in testis

Konrad, Lutz; Lüers, Georg H.; Völck-Badouin, Elke; Keilani, Marcel Munir; Laible, Leslie; Aumüller, Gerhard; Hofmann, Rainer

doi:10.1002/mrd.20399

Cited by 17 publications

(16 citation statements)

References 57 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, although T␤RII expression in the normal adrenal cortex has not been reported, the NCI-H295 adrenocortical cell line expresses T␤RII mRNA (49), and normal adrenocortical cells respond to TGF-␤ stimulation in vitro (50,51). With respect to T␤RII expression, TM3 and TM4 cells mimic not only their normal counterparts but also Sertoli cell lines and testicular tumors (31,32,52,53). Therefore, lack of the T␤RII-mediated mechanism for suppression of inhibin binding is probably uncommon.…”

Section: Discussionmentioning

confidence: 91%

Transforming Growth Factor-β Blocks Inhibin Binding to Different Target Cell Types in a Context-Dependent Manner through Dual Mechanisms Involving Betaglycan

et al. 2007

View full text Add to dashboard Cite

Inhibin antagonizes activin and bone morphogenetic protein actions by sequestering their type II receptors in high-affinity complexes with betaglycan, a coreceptor that inhibin shares with TGF-beta. To clarify the nature and extent of interactions between inhibin and TGF-beta, we therefore examined 1) the mutual competition between these ligands for binding, 2) the regulation of endogenous betaglycan expression by inhibin and TGF-beta isoforms, and 3) the consequences of such betaglycan regulation for subsequent inhibin binding in mouse Leydig (TM3), Sertoli (TM4), adrenocortical cancer (AC), and gonadotroph (LbetaT2) cell lines, chosen to model cellular targets for local and endocrine actions of inhibin. Recognized inhibin, activin, and TGF-beta binding proteins and TGF-beta/activin signaling components were expressed by all four cell types, but AC and LbetaT2 cells notably lacked the type II receptor for TGF-beta, TbetaRII. Overnight treatment of TM3 and TM4 cells with TGF-beta1 suppressed the levels of betaglycan mRNA by 73 and 46% of control and subsequent [(125)I]inhibin A binding by 64 and 41% of control (IC(50) of 54 and 92 pm), respectively. TGF-beta2 acted similarly. TGF-beta pretreatments commensurately decreased the [(125)I]inhibin A affinity labeling of betaglycan on TM3 and TM4 cells. TGF-beta isoforms as direct competitors blocked up to 60% of specific inhibin A binding sites on TM3 and TM4 cells but with 9- to 17-fold lower potency than when acting indirectly via regulation of betaglycan. Only the competitive action of TGF-beta was observed with TbetaRII-deficient AC and LbetaT2 cells. Neither inhibin A nor inhibin B regulated betaglycan mRNA or competed for binding of [(125)I]TGF-beta1 or -beta2. Thus, inhibin binding to its target cell types is controlled by TGF-beta through dual mechanisms of antagonism, the operation of which vary with cell context and display different sensitivities to TGF-beta. In contrast, TGF-beta binding is relatively insensitive to the presence of either inhibin A or inhibin B.

show abstract

Section: Discussionmentioning

confidence: 91%

Transforming Growth Factor-β Blocks Inhibin Binding to Different Target Cell Types in a Context-Dependent Manner through Dual Mechanisms Involving Betaglycan

et al. 2007

View full text Add to dashboard Cite

show abstract

“…This involves growth inhibition and extracellular matrix production [4]. In the testis, the TGFbs are localized to most cell types, as well as the TGFb receptor isoforms [45]. The expression of TGFb isoforms in the testis alters during development and can be influenced by other hormones and growth factors, as well as physiological conditions [46,47].…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor beta (TGFβ1, TGFβ2 and TGFβ3) null-mutant phenotypes in embryonic gonadal development

Memon

Anway

Covert

et al. 2008

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

The role transforming growth factor beta (TGFb) isoforms TGFb1, TGFb2 and TGFb3 have in the regulation of embryonic gonadal development was investigated with the use of null-mutant (i.e. knockout) mice for each of the TGFb isoforms. Late embryonic gonadal development was investigated because homozygote TGFb null-mutant mice generally die around birth, with some embryonic loss as well. In the testis, the TGFb1 null-mutant mice had a decrease in the number of germ cells at birth, postnatal day 0 (P0). In the testis, the TGFb2 null-mutant mice had a decrease in the number of seminiferous cords at embryonic day 15 (E15). In the ovary, the TGFb2 null-mutant mice had an increase in the number of germ cells at P0. TGFb isoforms appear to have a role in gonadal development, but interactions between the isoforms is speculated to compensate in the different TGFb isoform null-mutant mice.

show abstract

“…The receptor combinations for this growth factor are currently not known; however, TGF-β receptors are expressed both in sertoli cells and SSCs of the testis [98]. GDF3 functions in human and mouse ESCs to maintain pluripotency by inhibiting programs that are associated with stem cell differentiation [99,100].…”

Section: P Genes In Pathogenesis Of Tgctmentioning

confidence: 99%

The Stem Cell Identity of Testicular Cancer

Clark

2007

Stem Cell Rev

View full text Add to dashboard Cite

Testicular germ cell tumors account for 1% of all cancers, and are the most common malignancies to affect males between the ages of 15 and 34. Understanding the pathogenesis of testis cancer has been challenging because the molecular and cellular events that result in the formation of germ cell tumors are hypothesized to occur during human fetal development. In this review, the molecular pathways involved in human testis cancer will be presented based on our research in human embryonic stem cells (hESCs), and also research using animal models. Testis germ cell tumors are unique in that the normal germ cell from which the tumor is derived has distinct stem cell characteristics that are shared with pluripotent hESCs. In particular, normal fetal germ cells express the core pluripotent transcription factors NANOG, SOX2 and OCT4. In contrast to hESCs, the germ line is not pluripotent. As a result, germ cell tumorigenesis may arise from loss of germ line-specific inhibitors which in normal germ cells prevent overt pluripotency and self-renewal and when absent in abnormal germ cells, result in the conversion to germ line cancer stem cells. At the conclusion of this review, a model for the molecular events involved in germ cell tumor formation and the relationship between germ cell tumorigenesis and stem cell biology will be presented.

show abstract

Analysis of the mRNA expression of the TGF‐Beta family in testicular cells and localization of the splice variant TGF‐β2B in testis

Cited by 17 publications

References 57 publications

Transforming Growth Factor-β Blocks Inhibin Binding to Different Target Cell Types in a Context-Dependent Manner through Dual Mechanisms Involving Betaglycan

Transforming Growth Factor-β Blocks Inhibin Binding to Different Target Cell Types in a Context-Dependent Manner through Dual Mechanisms Involving Betaglycan

Transforming growth factor beta (TGFβ1, TGFβ2 and TGFβ3) null-mutant phenotypes in embryonic gonadal development

The Stem Cell Identity of Testicular Cancer

Contact Info

Product

Resources

About