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Dana Gaddy - One of the best experts on this subject based on the ideXlab platform.

  • regulation of osteoblastogenesis and osteoclastogenesis by the other reproductive hormones Activin and Inhibin
    Molecular and Cellular Endocrinology, 2009
    Co-Authors: Kristy M Nicks, Daniel S Perrien, Nisreen S Akel, Larry J Suva, Dana Gaddy
    Abstract:

    There is both cellular and physiological evidence demonstrating that both Activins and Inhibins regulate osteoblastogenesis and osteoclastogenesis, and regulate bone mass in vivo. Although Activins and Inhibins were initially isolated from the gonad, Activins are also produced and stored in bone, whereas Inhibins exert their regulation on bone cell differentiation and metabolism via endocrine effects. The accumulating data provide evidence that reproductive hormones, distinct from classical sex steroids, are important regulators of bone mass and bone strength. Given the well described dominant antagonism of Inhibin over Activin, as well as over BMPs and TGFβ, the gonadally derived Inhibins are important regulators of locally produced osteotrophic factors. Thus, the cycling Inhibins in females and diurnal changes in Inhibin B in males elicit temporal shifts in Inhibin levels (tone) that de-repress the pituitary. This fundamental action has the potential to de-repress locally stimulated changes in osteoblastogenesis and osteoclastogenesis, thereby altering bone metabolism.

  • Regulation of osteoblastogenesis and osteoclastogenesis by the other reproductive hormones, Activin and Inhibin.
    Molecular and cellular endocrinology, 2009
    Co-Authors: Kristy M Nicks, Daniel S Perrien, Nisreen S Akel, Larry J Suva, Dana Gaddy
    Abstract:

    There is both cellular and physiological evidence demonstrating that both Activins and Inhibins regulate osteoblastogenesis and osteoclastogenesis, and regulate bone mass in vivo. Although Activins and Inhibins were initially isolated from the gonad, Activins are also produced and stored in bone, whereas Inhibins exert their regulation on bone cell differentiation and metabolism via endocrine effects. The accumulating data provide evidence that reproductive hormones, distinct from classical sex steroids, are important regulators of bone mass and bone strength. Given the well described dominant antagonism of Inhibin over Activin, as well as over BMPs and TGFbeta, the gonadally derived Inhibins are important regulators of locally produced osteotrophic factors. Thus, the cycling Inhibins in females and diurnal changes in Inhibin B in males elicit temporal shifts in Inhibin levels (tone) that de-repress the pituitary. This fundamental action has the potential to de-repress locally stimulated changes in osteoblastogenesis and osteoclastogenesis, thereby altering bone metabolism.

Jennie P. Mather - One of the best experts on this subject based on the ideXlab platform.

  • Inhibins, Activins, their binding proteins and receptors: interactions underlying paracrine activity in the testis.
    Molecular and Cellular Endocrinology, 1994
    Co-Authors: Alison Moore, Lynne A. Krummen, Jennie P. Mather
    Abstract:

    Abstract The Inhibin-related peptides are present in the testis from early gestation through adulthood. They are produced from multiple testicular sites in a highly regulated manner, suggesting important paracrine roles. Similarly, receptors for these peptides are located in specific stages of the seminiferous tubule and on particular cell types, and an additional level of control is afforded by specific binding proteins, such as follistatin, which may regulate bioavailability. The actions of these factors include the modulation of interstitial cell function and the increase of spermatogonial proliferation in vitro. It thus appears that Activin and Inhibin are significant factors in the local control of testicular funtion.

  • localization of Inhibin and Activin binding sites in the testis during development by in situ ligand binding
    Biology of Reproduction, 1994
    Co-Authors: Lynne A. Krummen, Teresa K. Woodruff, Alison Moore, Robin Covello, Robin Taylor, Jennie P. Mather
    Abstract:

    : Inhibin and Activin are related proteins thought to be potential paracrine regulators of testicular development and maintenance of spermatogenesis. Messenger RNA and proteins immunologically related to both factors have been identified in the adult testis. However, the role(s) of these factors in paracrine regulation of testicular function is poorly understood. To identify potential targets for Inhibin and Activin in immature and adult testis, we used in situ binding of [125I]-labeled ligands to localize and describe the distribution of binding sites for Inhibin and Activin in testes of 15-, 18-, 21-, 30-, 45-, and 60-day-old rats. Nonspecific binding was defined as that occurring in the presence of a 1000-fold excess of unlabeled recombinant human (rh) Inhibin or Activin. [125I]-Inhibin was found to bind to interstitial cells throughout development. Inhibin binding was shown to co-localize with cells that showed positive staining for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). Competition studies demonstrated that this binding was indeed specific for Inhibin. In contrast, [125I]-Activin showed two distinct patterns of binding. First, [125I]-Activin was shown to bind in a non-stage-dependent manner to cells located in the basal compartment of the seminiferous tubules in testis obtained from animals of all ages studied. Binding of [125I]-Activin in the periphery of the tubule could be inhibited entirely by coincubation with excess unlabeled Activin and partially with excess unlabeled Inhibin. The ability of Inhibin to compete with Activin for binding appeared to be more pronounced in younger animals. In 45- and 60-day-old animals, a second stage-dependent component of [125I]-Activin binding was also apparent. This binding was localized to spermatids found in stage VII-VIII tubules and was inhibited by the presence of excess Activin, but not Inhibin. These results indicate that Inhibin can bind specifically to testicular interstitial cells throughout development and may be an important regulator of Leydig cell testosterone production or interstitial cell function. In contrast, Activin appears to bind in a specific and stage-dependent manner to receptors or high-affinity binding proteins on spermatids as well as to sites on the periphery of all seminiferous tubules. These results support the hypothesis that both Activin and Inhibin may act at several levels to regulate proliferation or differentiation of germ and Sertoli cell function as well as to modulate interstitial cell activity.

  • identification and characterization of binding proteins for Inhibin and Activin in human serum and follicular fluids
    Endocrinology, 1993
    Co-Authors: Lynne A. Krummen, Teresa K. Woodruff, Geralyn E Deguzman, Deborah L Baly, Elizabeth Mann, S Garg, Wai Lee Wong, Paul Cossum, Jennie P. Mather
    Abstract:

    Inhibins and Activins are produced by a variety of tissues and may have important endocrine and paracrine roles in development, reproduction, and hematopoiesis. However, little is known regarding the physical properties or concentrations of Inhibin and Activin in biological fluids. Binding proteins for Inhibin or Activin in serum or at production or target sites may have important implications for restricting the bioactivity of these hormones and may alter the immunoreactivity of these molecules in biological fluids. The objective of this study was to identify Inhibin- and Activin-binding proteins in human serum (HS) and follicular fluid (hFF) and determine the ability of these proteins to alter biological or immunological activity. In HS, [125I]Activin and Inhibin bound to a protein identified as alpha 2-macroglobulin (alpha 2M) using three criteria: 1) [125I]Inhibin and Activin bind purified alpha 2M, but not several other serum proteins tested; 2) complexes formed by [125I]Inhibin and Activin in HS and...

  • Activin Stimulates Spermatogonial Proliferation in Germ-Sertoli Cell Cocultures from Immature Rat Testis
    Endocrinology, 1990
    Co-Authors: Jennie P. Mather, Teresa K. Woodruff, Kenneth M. Attie, Glenn C. Rice, David M. Phillips
    Abstract:

    Activin and Inhibin are peptide hormones produced in the gonads which may act as autocrine and/or paracrine regulators of testicular function. Sertoli cells produce Inhibin, and it has recently been shown that Leydig cells can produce Activin in vitro. To further explore the local actions of Activin and Inhibin in the testis, Sertoli and germ cells were isolated from immature rats and cocultured in vitro. In these cultures we demonstrate that Activin A and Activin B, but not Inhibin A, stimulated spermatogonial proliferation in vitro. Activin increased [3H]thymidine incorporation 2- to 4-fold in cocultures after 48-72 h of treatment. Using autoradiography, the label was localized in the clusters of spermatogonia adhering to the Sertoli cell monolayer. Additionally, Activin stimulated a reaggregation of the cultures into tubule-like structures. Fluorescence-activated cytometry was used to analyze the cell population based on size, DNA content, and lipid content. Sertoli cells were identified using Nile Red...

Daniel S Perrien - One of the best experts on this subject based on the ideXlab platform.

  • regulation of osteoblastogenesis and osteoclastogenesis by the other reproductive hormones Activin and Inhibin
    Molecular and Cellular Endocrinology, 2009
    Co-Authors: Kristy M Nicks, Daniel S Perrien, Nisreen S Akel, Larry J Suva, Dana Gaddy
    Abstract:

    There is both cellular and physiological evidence demonstrating that both Activins and Inhibins regulate osteoblastogenesis and osteoclastogenesis, and regulate bone mass in vivo. Although Activins and Inhibins were initially isolated from the gonad, Activins are also produced and stored in bone, whereas Inhibins exert their regulation on bone cell differentiation and metabolism via endocrine effects. The accumulating data provide evidence that reproductive hormones, distinct from classical sex steroids, are important regulators of bone mass and bone strength. Given the well described dominant antagonism of Inhibin over Activin, as well as over BMPs and TGFβ, the gonadally derived Inhibins are important regulators of locally produced osteotrophic factors. Thus, the cycling Inhibins in females and diurnal changes in Inhibin B in males elicit temporal shifts in Inhibin levels (tone) that de-repress the pituitary. This fundamental action has the potential to de-repress locally stimulated changes in osteoblastogenesis and osteoclastogenesis, thereby altering bone metabolism.

  • Regulation of osteoblastogenesis and osteoclastogenesis by the other reproductive hormones, Activin and Inhibin.
    Molecular and cellular endocrinology, 2009
    Co-Authors: Kristy M Nicks, Daniel S Perrien, Nisreen S Akel, Larry J Suva, Dana Gaddy
    Abstract:

    There is both cellular and physiological evidence demonstrating that both Activins and Inhibins regulate osteoblastogenesis and osteoclastogenesis, and regulate bone mass in vivo. Although Activins and Inhibins were initially isolated from the gonad, Activins are also produced and stored in bone, whereas Inhibins exert their regulation on bone cell differentiation and metabolism via endocrine effects. The accumulating data provide evidence that reproductive hormones, distinct from classical sex steroids, are important regulators of bone mass and bone strength. Given the well described dominant antagonism of Inhibin over Activin, as well as over BMPs and TGFbeta, the gonadally derived Inhibins are important regulators of locally produced osteotrophic factors. Thus, the cycling Inhibins in females and diurnal changes in Inhibin B in males elicit temporal shifts in Inhibin levels (tone) that de-repress the pituitary. This fundamental action has the potential to de-repress locally stimulated changes in osteoblastogenesis and osteoclastogenesis, thereby altering bone metabolism.

F. H. De Jong - One of the best experts on this subject based on the ideXlab platform.

  • Expression of Activin and Inhibin subunits, receptors and binding proteins in human pheochromocytomas: a study based on mRNA analysis and immunohistochemistry.
    Clinical Endocrinology, 2007
    Co-Authors: Johannes Hofland, F.h. Van Nederveen, M.a. Timmerman, Esther Korpershoek, W. W. De Herder, Jacques W.m. Lenders, Albert A. J. Verhofstad, R.r. De Krijger, F. H. De Jong
    Abstract:

    OBJECTIVE: Pheochromocytomas are uncommon tumours arising from chromaffin cells of the adrenal medulla and related paraganglia. So far, one of the few reported markers to discriminate malignant from benign tumours is the betaB-subunit of Inhibin and Activin, members of the transforming growth factor (TGF)-beta superfamily of growth and differentiation factors. DESIGN: We investigated the expression of the mRNAs coding for Activin and Inhibin subunits, their receptors and binding proteins by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and studied the presence of the Inhibin betaB-subunit in human pheochromocytomas by immunohistochemistry. PATIENTS: Samples from resected pheochromocytomas of patients operated between 1973 and 2003 were used for experiments. RESULTS: The immunohistochemical investigations revealed that staining of the Inhibin betaB-subunit was positive in 12 of 36 (33%) benign and 5 of 34 (15%) malignant pheochromocytomas (P > 0.05). Therefore, it was not possible to discriminate between benign and malignant tumours solely on the basis of Inhibin betaB-subunit immunohistochemistry. Quantitative real-time RT-PCR in nine benign and four malignant tumours showed expression of Inhibin alpha-, betaA- and betaB-subunits, the Activin receptors Alk-4, ActRIIA, and ActRIIB, and the Inhibin- and Activin-binding proteins betaglycan and follistatin in all samples. No correlations were detected between individually coupled expression of mRNAs of these Activin- and Inhibin-related genes in the 13 pheochromocytomas. Only Inhibin betaA-subunit expression was different in malignant compared to benign pheochromocytomas (P = 0.020). CONCLUSIONS: No clear role for Activin and Inhibin was found in discriminating between benign and malignant pheochromocytomas.

  • expression of Activin and Inhibin subunits receptors and binding proteins in human adrenocortical neoplasms
    Clinical Endocrinology, 2006
    Co-Authors: Johannes Hofland, M.a. Timmerman, W. W. De Herder, R.r. De Krijger, R H N Van Schaik, F. H. De Jong
    Abstract:

    Summary Objective  The growth and differentiation factors Activin and Inhibin can affect tumour formation and steroid production in the adrenal cortex. These factors bind to type I (Alk-4), type II (ActRIIA, ActRIIB) and type III (betaglycan) receptors or to the Activin-binding protein follistatin. Expression of these Activin-related mRNAs was measured in different types of adrenocortical tissues and tumours to study the relationship with tumorigenesis. Design  Quantitative expression of Activin-related mRNAs was investigated in patient adrenocortical samples. Patients  Twenty-eight human adrenocortical samples from normal and hyperplastic adrenals and from adrenocortical adenomas and carcinomas were collected after surgery for study purposes. Measurements  Using quantitative reverse transcription polymerase chain reaction (RT-PCR), we investigated the expression of Inhibin α-, βA- and βB-subunits, follistatin, betaglycan, ActRIIA, ActRIIB and Alk-4 in the adrenocortical tissues. The expression of cytochrome P450c17 (CYP17) mRNA was also measured to investigate its association with Inhibin and Activin subunit expression. Results  All genes studied were expressed in all tissues, with the exception of the Inhibin α-subunit in one hyperplastic adrenal and three adrenocortical carcinomas. Expression of Inhibin βA-subunit, follistatin, betaglycan, ActRIIA, ActRIIB and CYP17 differed between nontumorous adrenals and carcinomas. Conclusions  These differences, together with correlation analysis, indicate parallel regulation of the expression of CYP17, the Inhibin α-subunit, ActRIIA, ActRIIB, betaglycan and follistatin. We conclude that the expression of Activin and Inhibin subunits, receptors and binding proteins is affected by tumour formation in the adrenal gland and may play a role in tumorigenesis.

  • Human testicular germ cell tumours express Inhibin subunits, Activin receptors and follistatin mRNAs
    British Journal of Cancer, 1997
    Co-Authors: Rh Van Schaik, Cd Wierikx, Lh Looijenga, Jw Oosterhuis, F. H. De Jong
    Abstract:

    Germ cell development is influenced by Activin and Inhibin, which are produced by Sertoli cells. Activin also affects differentiation of mouse embryonal carcinoma cells, which, to a certain extent, resemble the embryonal carcinoma component of germ cell tumours. Therefore, the expression of Inhibin/Activin subunits, of Activin receptors and of the Activin-binding protein follistatin was studied in testicular germ cell tumours, using RNAase protection assays. Testicular germ cell tumours of adolescents and adults (TGCTs) and spermatocytic seminomas expressed Activin type I and type II receptors (ActRI and ActRII respectively). Seminomas expressed significantly lower levels of ActRIIA (P

Wylie Vale - One of the best experts on this subject based on the ideXlab platform.

  • 4 Activins and Inhibins
    Cold Spring Harbor Monograph Archive, 2020
    Co-Authors: Ezra Wiater, Wylie Vale
    Abstract:

    Activins and the structurally and functionally related Inhibins belong to the transforming growth factor-β (TGF-β) family of growth factors. Activins and Inhibins have central roles in regulating follicle-stimulating hormone (FSH) release and in coordinating reproductive physiology. Inhibins function as classical endocrine hormones, whereas both Activins and Inhibins have localized autocrine and paracrine roles. Activins have additional functions outside of the reproductive systems as regulators of cell growth and differentiation, particularly in response to injury and inflammation. This chapter discusses the mechanisms involved in Activin and Inhibin activities and the roles of these factors in reproductive and other tissues. STRUCTURES and SYNTHESIS OF ActivinS and InhibinS A hormone termed “Inhibin” was proposed to exist in 1932 (McCullagh 1932). Inhibin was defined as a nonsteroidal, water-soluble factor in gonadal extracts that prevents stereotypical changes in the morphology of the pituitary that appeared after castration. After the identification of the pituitary cell types and their corresponding hormones, this definition was refined: Inhibin exerts a direct effect on pituitary gonadotrope cells, leading to a specific suppression of FSH release, without altering the release of luteinizing hormone (LH) (de Kretser et al. 1988; Vale et al. 1988). Biochemical purification of Inhibin was undertaken using this activity on pituitary cells as an assay. Secretions of various gonadal fluids were found to be rich sources of Inhibin and were thus used as source material for purification. Inhibins—and in the process, Activins—were eventually purified to apparent homogeneity from these sources based on their effects on FSH...

  • Erratum to “Antagonism of Activin by Inhibin and Inhibin receptors: a functional role for betaglycan-glycan”
    Molecular and Cellular Endocrinology, 2002
    Co-Authors: Peter C Gray, Louise M Bilezikjian, Wylie Vale
    Abstract:

    Activin and Inhibin research has provided important insight into reproductive physiology as well as many areas involving regulation of cell growth, differentiation and function. Progress in understanding the roles of these hormones in various cell and tissue types has been complimented by novel discoveries at the molecular level that have shed light on ligand/receptor interactions, signaling mechanisms and regulation. While the receptors and signaling pathway for Activin are now well characterized, the molecular basis for Inhibin action has remained relatively unclear. Here we summarize recent advances in understanding Inhibin’s mode of action focusing on our recent identification of betaglycan as an Inhibin co-receptor capable of mediating Inhibin action. © 2001 Elsevier Science Ireland Ltd. All rights reserved.

  • antagonism of Activin by Inhibin and Inhibin receptors a functional role for betaglycan glycan
    Molecular and Cellular Endocrinology, 2001
    Co-Authors: Peter C Gray, Louise M Bilezikjian, Wylie Vale
    Abstract:

    Abstract Activin and Inhibin research has provided important insight into reproductive physiology as well as many areas involving regulation of cell growth, differentiation and function. Progress in understanding the roles of these hormones in various cell and tissue types has been complimented by novel discoveries at the molecular level that have shed light on ligand/receptor interactions, signaling mechanisms and regulation. While the receptors and signaling pathway for Activin are now well characterized, the molecular basis for Inhibin action has remained relatively unclear. Here we summarize recent advances in understanding Inhibin's mode of action focusing on our recent identification of betaglycan-glycan as an Inhibin co-receptor capable of mediating Inhibin action.

  • identification of a binding site on the type ii Activin receptor for Activin and Inhibin
    Journal of Biological Chemistry, 2000
    Co-Authors: Peter C Gray, Cynthia J. Donaldson, Jason Greenwald, Senyon Choe, Amy L Blount, Koichi S Kunitake, Wylie Vale
    Abstract:

    Abstract Type II Activin receptors (ActRII and ActRIIB) are single-transmembrane domain serine/threonine kinase receptors that bind Activin to initiate the signaling and cellular responses triggered by this hormone. Inhibin also binds type II Activin receptors and antagonizes many Activin effects. Here we describe alanine scanning mutagenesis of the ActRII extracellular domain. We identify a cluster of three hydrophobic residues (Phe42, Trp60, and Phe83) that, when individually mutated to alanine in the context of the full-length receptor, cause the disruption of Activin and Inhibin binding to ActRII. Each of the alanine-substituted ActRII mutants retaining Activin binding maintains the ability to form cross-linked complexes with Activin and supports Activin cross-linking to the type I Activin receptor ALK4. Unlike wild-type ActRII, the three mutants unable to bind Activin do not cause an increase in Activin signaling when transiently expressed in a corticotroph cell line. Together, our results implicate these residues in forming a critical binding surface on ActRII required for functional interactions with both Activin and Inhibin. This first identification of a transforming growth factor-β family member binding site may provide a general basis for characterizing binding sites for other members of the superfamily.

  • Activin and Inhibin Binding to the Soluble Extracellular Domain of Activin Receptor II
    Endocrinology, 1999
    Co-Authors: Cynthia J. Donaldson, Joan Vaughan, A. Corrigan, Wolfgang H Fischer, Wylie Vale
    Abstract:

    Activins and Inhibins belong to the transforming growth factor-β-like superfamily of growth and differentiation factors that exert pleiotropic effects in many target tissues. Heteromeric association of Activin with two structurally related receptor serine/threonine kinases, Activin receptor types I and II, initiates downstream signaling events. The extracellular domain of type II mouse Activin receptor (ActRII ECD) was expressed in the baculovirus system, purified in three steps by lectin affinity, anion exchange, and reverse phase chromatography, and further characterized by mass spectrometry. The reduction in the apparent size of the purified ActRII ECD on SDS-PAGE after treatment with glycosidases provided evidence for N- and O-linked oligosaccharides. Specific receptor/ligand complexes of [125I]Activin A to ActRII ECD or [125I]ActRII ECD to Activin A were analyzed by cross-linking and immunoprecipitation. Two major radiolabeled bands were observed on SDS-PAGE with mobilities consistent with the expect...