The Experts below are selected from a list of 189 Experts worldwide ranked by ideXlab platform

Jan Bogerd - One of the best experts on this subject based on the ideXlab platform.

  • Fsh Stimulates Spermatogonial Proliferation and Differentiation in Zebrafish via Igf3.
    Endocrinology, 2015
    Co-Authors: Rafael Henrique Nobrega, Paul P. De Waal, Rüdiger W. Schulz, D. Crespo, R. D. V. S. Morais, L. R. França, Jan Bogerd
    Abstract:

    Growth factors modulate germ line stem cell self-renewal and differentiation behavior. We investigate the effects of Igf3, a fish-specific member of the igf family. Fsh increased in a steroid-independent manner the number and mitotic index of single type A undifferentiated spermatogonia and of clones of type A differentiating spermatogonia in adult zebrafish testis. All 4 igf gene family members in zebrafish are expressed in the testis but in tissue culture only igf3 transcript levels increased in response to recombinant zebrafish Fsh. This occurred in a cAMP/protein kinase A-dependent manner, in line with the results of studies on the igf3 gene promoter. Igf3 protein was detected in Sertoli cells. Recombinant zebrafish Igf3 increased the mitotic index of type A undifferentiated and type A differentiating spermatogonia and up-regulated the expression of genes related to spermatogonial differentiation and entry into meiosis, but Igf3 did not modulate testicular Androgen Release. An Igf receptor inhibitor blocked these effects of Igf3. Importantly, the Igf receptor inhibitor also blocked Fsh-induced spermatogonial proliferation. We conclude that Fsh stimulated Sertoli cell production of Igf3, which promoted via Igf receptor signaling spermatogonial proliferation and differentiation and their entry into meiosis. Because previous work showed that Fsh also Released spermatogonia from an inhibitory signal by down-regulating anti-Mullerian hormone and by stimulating Androgen production, we can now present a model, in which Fsh orchestrates the activity of stimulatory (Igf3, Androgens) and inhibitory (anti-Mullerian hormone) signals to promote spermatogenesis.

  • Thyroid Hormone Stimulates the Proliferation of Sertoli Cells and Single Type A Spermatogonia in Adult Zebrafish (Danio rerio) Testis
    Endocrinology, 2013
    Co-Authors: R. D. V. S. Morais, Jan Bogerd, Rafael Henrique Nobrega, L. R. França, N. E. Gómez-gonzález, Ruben Schmidt, Rüdiger W. Schulz
    Abstract:

    Thyroid hormones participate in regulating growth and homeostatic processes in vertebrates, including development and adult functioning of the reproductive system. Here we report a new stimulatory role of thyroid hormone on the proliferation of Sertoli cells (SCs) and single, type A undifferentiated spermatogonia (A(und)) in adult zebrafish testes. A role for T3 in zebrafish testis is suggested by in situ hybridization studies, which localized thyroid receptor α (thrα) in SCs and the β (thrβ) mRNA in Sertoli and Leydig cells. Using a primary zebrafish testis tissue culture system, the effect of T3 on steroid Release, spermatogenesis, and the expression of selected genes was evaluated. Basal steroid Release and Leydig cell gene expression did not change in response to T3. However, in the presence of FSH, T3 potentiated gonadotropin-stimulated Androgen Release as well as Androgen receptor (ar) and 17α-hydroxylase/17,20 lyase (cyp17a1) gene expression. Moreover, T3 alone stimulated the proliferation of both SCs and A(und), potentially resulting in newly formed spermatogonial cysts. Additional tissue culture studies demonstrated that Igf3, a new, gonad-specific member of the IGF family, mediated the stimulatory effect of T3 on the proliferation of A(und) and SCs. Finally, T3 induced changes in connexin 43 mRNA levels in the testis, a known T3-responsive gene. Taken together, our studies suggest that T3 expands the population of SCs and A(und) involving Igf signaling and potentiates gonadotropin-stimulated testicular Androgen production as well as Androgen sensitivity.

  • Sertoli cell proliferation in the adult testis is induced by unilateral gonadectomy in African catfish
    General and comparative endocrinology, 2012
    Co-Authors: Rüdiger W. Schulz, Ángel García-lópez, Wytske Van Dijk, L. R. França, Elena Chaves-pozo, Jan Bogerd
    Abstract:

    Abstract Survival and development of male germ cells depends on their close contact with Sertoli cells. In the cystic spermatogenesis found in fish, one germ cell clone, initially a single undifferentiated spermatogonium type A, is enclosed by and accompanied through spermatogenesis by a group of Sertoli cells. Previous work showed that after forming such spermatogenic cysts, Sertoli cells proliferated mainly during the mitotic expansion of the spermatogonial clone in the cyst. Here, we used unilateral gonadectomy (ULG) as experimental model to study Sertoli cell proliferation at the start of cyst development in adult African catfish testis. Four days after surgery, we observed a particularly strong increase in the number of mitotic Sertoli cells along with a significant increase in the number of mitotic single type A spermatogonia. Proliferation of pairs of spermatogonia or of larger germ cell clones, however, did not change. At the same time, pituitary transcript levels of the three gonadotropin-subunits ( cga , glycoprotein hormones, alpha polypeptide; fshb , follicle stimulating hormone, beta polypeptide; lhb , luteinizing hormone, beta polypeptide) were not different between sham-operated and ULG males. However, expression of the gonadotropin-releasing hormone receptor gene gnrhr1 was significantly reduced after ULG, and Lh plasma levels were slightly elevated. In the testis remaining after ULG, Fsh receptor ( fshr ) mRNA levels increased significantly but luteinizing hormone/choriogonadotropin receptor ( lhcgr ) mRNA levels did not change. Circulating Androgen levels did not differ between groups, but testicular Androgen Release increased significantly 2- to 3-fold after ULG. Considering the strong steroidogenic potency of Fsh and the expression of the fshr gene by Leydig cells in catfish, we explain the absence of an effect of ULG on circulating Androgen levels by an Fshr-mediated, compensatory increase in the steroid production of the remaining testis, perhaps supported in addition by the increased Lh plasma levels. Since Fsh is a major stimulator of mammalian Sertoli cell proliferation, we propose that ULG-induced activation of the Fsh signalling system also promoted Sertoli cell proliferation and – possibly as a consequence of that – proliferation of single type A spermatogonia, providing the basis for an increased spermatogenic capacity.

  • studies in zebrafish reveal unusual cellular expression patterns of gonadotropin receptor messenger ribonucleic acids in the testis and unexpected functional differentiation of the gonadotropins
    Endocrinology, 2010
    Co-Authors: Angel Garcialopez, Geir Lasse Taranger, Paul P. De Waal, Hugo R De Jonge, Rafael Henrique Nobrega, Wytske Van Dijk, Wieger Hemrika, Jan Bogerd
    Abstract:

    This study aimed to improve, using the zebrafish model, our understanding of the distinct roles of pituitary gonadotropins FSH and LH in regulating testis functions in teleost fish. We report, for the first time in a vertebrate species, that zebrafish Leydig cells as well as Sertoli cells express the mRNAs for both gonadotropin receptors (fshr and lhcgr). Although Leydig cell fshr expression has been reported in other piscine species and may be a common feature of teleost fish, Sertoli cell lhcgr expression has not been reported previously and might be related to the undifferentiated gonochoristic mode of gonadal sex differentiation in zebrafish. Both recombinant zebrafish (rzf) gonadotropins (i.e. rzfLH and rzfFSH) stimulated Androgen Release in vitro and in vivo, with rzfFSH being significantly more potent than rzfLH. Forskolin-induced adenylate cyclase activation mimicked, whereas the protein kinase A inhibitor H-89 significantly reduced, the gonadotropin-stimulated Androgen Release. Therefore, we conclude that both FSH receptor and LH/choriogonadotropin receptor signaling are predominantly mediated through the cAMP/protein kinase A pathway to promote steroid production. Despite this similarity, other downstream mechanisms seem to differ. For example, rzfFSH up-regulated the testicular mRNA levels of a number of steroidogenesis-related genes both in vitro and in vivo, whereas rzfLH or human chorionic gonadotropin did not. Although not fully understood at present, these differences could explain the capacity of FSH to support both steroidogenesis and spermatogenesis on a long-term basis, whereas LH-stimulated steroidogenesis might be a more acute process, possibly restricted to periods during which peak steroid levels are required.

  • Oestrogen-induced Androgen insufficiency results in a reduction of proliferation and differentiation of spermatogonia in the zebrafish testis.
    The Journal of endocrinology, 2009
    Co-Authors: Paul P. De Waal, Marcelo C Leal, Nathalie Hinfray, François Brion, Ángel García-lópez, Rüdiger W. Schulz, Hugo R De Jonge, Sergio Liarte, Jan Bogerd
    Abstract:

    Androgens can induce complete spermatogenesis in immature or prepubertal teleost fish. However, many aspects of the role of Androgens in adult teleost spermatogenesis have remained elusive. Since oestrogens inhibit Androgen synthesis, we used an oestrogen-induced Androgen depletion model to identify Androgen-dependent stages during adult zebrafish spermatogenesis. Exposure to 10 nM 17beta-oestradiol (E(2)) in vivo at least halved the mass of differentiating germ cells (from type B spermatogonia to spermatids), while type A spermatogonia accumulated. Studies on the cellular dynamics revealed that a reduction of spermatogonial proliferation together with an inhibition of their differentiation to type B spermatogonia were the basis for the oestrogen-mediated disturbance of spermatogenesis. The capacity of the zebrafish testis to produce 11-ketotestosterone as well as the expression of steroidogenesis-related genes was markedly decreased after in vivo oestrogen exposure. Moreover, the Androgen-Release response to recombinant zebrafish Lh was lost after oestrogen exposure. We conclude that oestrogen exposure caused a state of Androgen insufficiency in adult male zebrafish. Since the downregulation of the steroidogenic system as well as the disturbance of spermatogenesis in testicular explants exposed to E(2) ex vivo was much less severe than after in vivo exposure, the main inhibitory effect appears to be exerted via feedback inhibition of gonadotropin Release. This experimental set-up helped to identify spermatogonial proliferation and their differentiation as Androgen targets in adult zebrafish spermatogenesis.

Rüdiger W. Schulz - One of the best experts on this subject based on the ideXlab platform.

  • Fsh Stimulates Spermatogonial Proliferation and Differentiation in Zebrafish via Igf3.
    Endocrinology, 2015
    Co-Authors: Rafael Henrique Nobrega, Paul P. De Waal, Rüdiger W. Schulz, D. Crespo, R. D. V. S. Morais, L. R. França, Jan Bogerd
    Abstract:

    Growth factors modulate germ line stem cell self-renewal and differentiation behavior. We investigate the effects of Igf3, a fish-specific member of the igf family. Fsh increased in a steroid-independent manner the number and mitotic index of single type A undifferentiated spermatogonia and of clones of type A differentiating spermatogonia in adult zebrafish testis. All 4 igf gene family members in zebrafish are expressed in the testis but in tissue culture only igf3 transcript levels increased in response to recombinant zebrafish Fsh. This occurred in a cAMP/protein kinase A-dependent manner, in line with the results of studies on the igf3 gene promoter. Igf3 protein was detected in Sertoli cells. Recombinant zebrafish Igf3 increased the mitotic index of type A undifferentiated and type A differentiating spermatogonia and up-regulated the expression of genes related to spermatogonial differentiation and entry into meiosis, but Igf3 did not modulate testicular Androgen Release. An Igf receptor inhibitor blocked these effects of Igf3. Importantly, the Igf receptor inhibitor also blocked Fsh-induced spermatogonial proliferation. We conclude that Fsh stimulated Sertoli cell production of Igf3, which promoted via Igf receptor signaling spermatogonial proliferation and differentiation and their entry into meiosis. Because previous work showed that Fsh also Released spermatogonia from an inhibitory signal by down-regulating anti-Mullerian hormone and by stimulating Androgen production, we can now present a model, in which Fsh orchestrates the activity of stimulatory (Igf3, Androgens) and inhibitory (anti-Mullerian hormone) signals to promote spermatogenesis.

  • Azole fungicides in zebrafish: new effects for old molecules
    2015
    Co-Authors: Nathalie Hinfray, Rüdiger W. Schulz, Yann Guiguen, François Brion
    Abstract:

    Azole is a class of diverse compounds discovered several decades ago and essentially used as antifungals in agriculture and medicine. Their primary mode of action is to inhibit the fungal enzyme 14α-demethylase, which produces ergosterol, an important component of the cell membranes of fungi. Despite this specific mode of action, azoles are also characterized by their capacity to disrupt the endocrine system of vertebrate through multiple mechanisms notably by altering steroidogenesis, a key physiological process responsible for the biosynthesis of steroidal hormones. For instance, azole compounds affect both expression and enzymatic activities of several steroidogenic enzymes in vertebrate models, including fish, leading to reproductive disorders. Because of their uses, their presence in the aquatic environment (surface waters of rivers, lakes and estuaries; sewage sludge) has been recently reported in different industrialized countries raising the need to assess hazard and risk posed to aquatic organisms. In this context, several experiments have been performed to explore the effects of the pharmaceutical azole, clotrimazole, on the endocrine system in the zebrafish. In males, we found that clotrimazole was able to affect the testicular physiology by affecting steroidogenesis, Androgen Release and spermatogenesis (Hinfray et al., 2011, Baudiffier et al. 2012, 2013). However, the most striking effect was observed in females. Indeed, we found that exposure of adult female zebrafish to clotrimazole led to a dramatic masculinisation as revealed by the complete sex-reversal of the phenotypic sex. Remarkably, this sex-reversal occurred rapidly leading to well-differentiated testicular tissue after 42 days of exposure. By using cyp19a1a-GFP transgenic zebrafish, we further demonstrated that clotrimazole led to a time-dependent inhibition of GFP expression in ovary which preceded the histological differentiation of testis demonstrating the crucial role played by aromatase in the process of masculinisation. Altogether, our study demonstrates that clotrimazole significantly affect the gonad endocrinology and physiology of fish revealing new and striking effects on its ability to reverse the phenotypic sex of adult female. Based on our data, it is clear that further studies are needed to address the issue raised by the presence of azoles in the aquatic environment as regards to their potential impact on wild population of fish.

  • Thyroid Hormone Stimulates the Proliferation of Sertoli Cells and Single Type A Spermatogonia in Adult Zebrafish (Danio rerio) Testis
    Endocrinology, 2013
    Co-Authors: R. D. V. S. Morais, Jan Bogerd, Rafael Henrique Nobrega, L. R. França, N. E. Gómez-gonzález, Ruben Schmidt, Rüdiger W. Schulz
    Abstract:

    Thyroid hormones participate in regulating growth and homeostatic processes in vertebrates, including development and adult functioning of the reproductive system. Here we report a new stimulatory role of thyroid hormone on the proliferation of Sertoli cells (SCs) and single, type A undifferentiated spermatogonia (A(und)) in adult zebrafish testes. A role for T3 in zebrafish testis is suggested by in situ hybridization studies, which localized thyroid receptor α (thrα) in SCs and the β (thrβ) mRNA in Sertoli and Leydig cells. Using a primary zebrafish testis tissue culture system, the effect of T3 on steroid Release, spermatogenesis, and the expression of selected genes was evaluated. Basal steroid Release and Leydig cell gene expression did not change in response to T3. However, in the presence of FSH, T3 potentiated gonadotropin-stimulated Androgen Release as well as Androgen receptor (ar) and 17α-hydroxylase/17,20 lyase (cyp17a1) gene expression. Moreover, T3 alone stimulated the proliferation of both SCs and A(und), potentially resulting in newly formed spermatogonial cysts. Additional tissue culture studies demonstrated that Igf3, a new, gonad-specific member of the IGF family, mediated the stimulatory effect of T3 on the proliferation of A(und) and SCs. Finally, T3 induced changes in connexin 43 mRNA levels in the testis, a known T3-responsive gene. Taken together, our studies suggest that T3 expands the population of SCs and A(und) involving Igf signaling and potentiates gonadotropin-stimulated testicular Androgen production as well as Androgen sensitivity.

  • Effect of in vivo chronic exposure to clotrimazole on zebrafish testis function
    Environmental science and pollution research international, 2013
    Co-Authors: Damien Baudiffier, Nathalie Hinfray, Nicolas Creusot, Edith Chadili, Jean-marc Porcher, Rüdiger W. Schulz, Catherine Ravaud, François Brion
    Abstract:

    Clotrimazole is an azole fungicide used as a human pharmaceutical that is known to inhibit cytochrome P450 (CYP) enzymatic activities, including several steroidogenic CYP. In a previous report, we showed that a 7-day exposure to clotrimazole induced the expression of genes related to steroidogenesis in the testes as a compensatory response, involving the activation of the Fsh/Fshr pathway. In this context, the aim of the present study was to assess the effect of an in vivo 21-day chronic exposure to clotrimazole (30–197 μg/L) on zebrafish testis function, i.e., spermatogenesis and Androgen Release. The experimental design combined (1) gene transcript levels measurements along the brain–pituitary–gonad axis, (2) 11-ketotestosterone (11-KT) quantification in the blood, and (3) histology of the testes, including morphometric analysis. The chronic exposure led to an induction of steroidogenesis-related genes and fshr in the testes as well as fshβ in the pituitary. Moreover, increases of the gonadosomatic index and of the volume proportion of interstitial Leydig cells were observed in clotrimazole-exposed fish. In accordance with these histological observations, the circulating concentration of 11-KT had increased. Morphometric analysis of the testes did not show an effect of clotrimazole on meiotic (spermatocytes) or postmeiotic (spermatids and spermatozoa) stages, but we observed an increase in the number of type A spermatogonia, in agreement with an increase in mRNA levels of piwil1, a specific molecular marker of type A spermatogonia. Our study demonstrated that clotrimazole is able to affect testicular physiology and raised further concern about the impact of clotrimazole on reproduction.

  • Sertoli cell proliferation in the adult testis is induced by unilateral gonadectomy in African catfish
    General and comparative endocrinology, 2012
    Co-Authors: Rüdiger W. Schulz, Ángel García-lópez, Wytske Van Dijk, L. R. França, Elena Chaves-pozo, Jan Bogerd
    Abstract:

    Abstract Survival and development of male germ cells depends on their close contact with Sertoli cells. In the cystic spermatogenesis found in fish, one germ cell clone, initially a single undifferentiated spermatogonium type A, is enclosed by and accompanied through spermatogenesis by a group of Sertoli cells. Previous work showed that after forming such spermatogenic cysts, Sertoli cells proliferated mainly during the mitotic expansion of the spermatogonial clone in the cyst. Here, we used unilateral gonadectomy (ULG) as experimental model to study Sertoli cell proliferation at the start of cyst development in adult African catfish testis. Four days after surgery, we observed a particularly strong increase in the number of mitotic Sertoli cells along with a significant increase in the number of mitotic single type A spermatogonia. Proliferation of pairs of spermatogonia or of larger germ cell clones, however, did not change. At the same time, pituitary transcript levels of the three gonadotropin-subunits ( cga , glycoprotein hormones, alpha polypeptide; fshb , follicle stimulating hormone, beta polypeptide; lhb , luteinizing hormone, beta polypeptide) were not different between sham-operated and ULG males. However, expression of the gonadotropin-releasing hormone receptor gene gnrhr1 was significantly reduced after ULG, and Lh plasma levels were slightly elevated. In the testis remaining after ULG, Fsh receptor ( fshr ) mRNA levels increased significantly but luteinizing hormone/choriogonadotropin receptor ( lhcgr ) mRNA levels did not change. Circulating Androgen levels did not differ between groups, but testicular Androgen Release increased significantly 2- to 3-fold after ULG. Considering the strong steroidogenic potency of Fsh and the expression of the fshr gene by Leydig cells in catfish, we explain the absence of an effect of ULG on circulating Androgen levels by an Fshr-mediated, compensatory increase in the steroid production of the remaining testis, perhaps supported in addition by the increased Lh plasma levels. Since Fsh is a major stimulator of mammalian Sertoli cell proliferation, we propose that ULG-induced activation of the Fsh signalling system also promoted Sertoli cell proliferation and – possibly as a consequence of that – proliferation of single type A spermatogonia, providing the basis for an increased spermatogenic capacity.

Rafael Henrique Nobrega - One of the best experts on this subject based on the ideXlab platform.

  • Thyroid hormone actions on male reproductive system of teleost fish.
    General and comparative endocrinology, 2018
    Co-Authors: Aldo Tovo-neto, Maira Da Silva Rodrigues, Hamid R. Habibi, Rafael Henrique Nobrega
    Abstract:

    Abstract Thyroid hormones (THs) play important roles in the regulation of many biological processes of vertebrates, such as growth, metabolism, morphogenesis and reproduction. An increasing number of studies have been focused on the involvement of THs in the male reproductive system of vertebrates, in particular of fish. Therefore, this mini-review aims to summarize the main findings on THs role in male reproductive system of fish, focusing on sex differentiation, testicular development and spermatogenesis. The existing data in the literature have demonstrated that THs exert their roles at the different levels of the hypothalamic-pituitary-gonadal (HPG) axis. In general a positive correlation has been shown between THs and fish reproductive status; where THs are associated with testicular development, growth and maturation. Recently, the molecular mechanisms underlying the role of THs in spermatogenesis have been unraveled in zebrafish testis. THs promote germ cell proliferation and differentiation by increasing a stimulatory growth factor of spermatogenesis produced by Sertoli cells. In addition, THs enhanced the gonadotropin-induced Androgen Release in zebrafish testis. Next to their functions in the adult testis, THs are involved in the gonadal sex differentiation through modulating sex-related gene expression, and testicular development via regulation of Sertoli cell proliferation. In conclusion, this mini-review showed that THs modulate the male reproductive system during the different life stages of fish. The physiological and molecular mechanisms showed a link between the thyroid and reproduction, suggesting a possibly co-evolution and interdependence of these two systems.

  • Fsh Stimulates Spermatogonial Proliferation and Differentiation in Zebrafish via Igf3.
    Endocrinology, 2015
    Co-Authors: Rafael Henrique Nobrega, Paul P. De Waal, Rüdiger W. Schulz, D. Crespo, R. D. V. S. Morais, L. R. França, Jan Bogerd
    Abstract:

    Growth factors modulate germ line stem cell self-renewal and differentiation behavior. We investigate the effects of Igf3, a fish-specific member of the igf family. Fsh increased in a steroid-independent manner the number and mitotic index of single type A undifferentiated spermatogonia and of clones of type A differentiating spermatogonia in adult zebrafish testis. All 4 igf gene family members in zebrafish are expressed in the testis but in tissue culture only igf3 transcript levels increased in response to recombinant zebrafish Fsh. This occurred in a cAMP/protein kinase A-dependent manner, in line with the results of studies on the igf3 gene promoter. Igf3 protein was detected in Sertoli cells. Recombinant zebrafish Igf3 increased the mitotic index of type A undifferentiated and type A differentiating spermatogonia and up-regulated the expression of genes related to spermatogonial differentiation and entry into meiosis, but Igf3 did not modulate testicular Androgen Release. An Igf receptor inhibitor blocked these effects of Igf3. Importantly, the Igf receptor inhibitor also blocked Fsh-induced spermatogonial proliferation. We conclude that Fsh stimulated Sertoli cell production of Igf3, which promoted via Igf receptor signaling spermatogonial proliferation and differentiation and their entry into meiosis. Because previous work showed that Fsh also Released spermatogonia from an inhibitory signal by down-regulating anti-Mullerian hormone and by stimulating Androgen production, we can now present a model, in which Fsh orchestrates the activity of stimulatory (Igf3, Androgens) and inhibitory (anti-Mullerian hormone) signals to promote spermatogenesis.

  • Spermatogonial stem cells and their endocrine and paracrine regulation in zebrafish
    2014
    Co-Authors: Rafael Henrique Nobrega
    Abstract:

    In stem cell biology, the term niche refers to anatomical and functional dimensions where stem cell populations are established and can be maintained. In these specific places, stem cells are protected from differentiating signals that otherwise might lead to their depletion, and also protected from overproliferation. To achieve this, the cells forming the niche (in the testis: Sertoli cells and interstitial cell types)integrate signals from different sources and produce regulatory output modulating stem cell behavior as necessary for sustaining tissue homeostasis. In this thesis, we studied spermatogonial stem cell (SSC) candidates, their niche, and endocrine and paracrine signals modulating SSC activity in zebrafish. In zebrafish testis, the anatomical location of SSCs was identified by the “label retaining cell” approach. Two populations of SSC candidates (“active” and “reserve”) were found surrounded by Sertoli cells near the interstitial compartment. It is assumed that the vertebrate SSC niche integrates signals from Sertoli cells, and from interstitial elements (Leydig cell, myoid, blood vessels) to regulate the SSC activity, also in the zebrafish testes. The stemness and sexual plasticity of these SSC candidates was confirmed by transplantation assays, showing colonization and donor-derived spermatogenesis as well as oogenesis in recipient testis and ovaries. To broaden our knowledge about the functional aspects of the niche (signals), SSCs were activated by treating adult males with a cytostatic agent, and gene expression studies revealed an opposing effect on two growth factors expressed in Sertoli cells, the TGFβ family member Amh (anti-Mullerian hormone), and Igf3 (insulin-like growth factor 3). Recombinant Amh and Igf3 were produced and tested on zebrafish testis explants: Amh blocked spermatogonial differentiation, decreased the proliferation of type A spermatogonia, and moreover compromised Leydig cell Androgen Release activated by follicle-stimulating hormone (Fsh). Igf3, on the other hand, stimulated spermatogonial proliferation and differentiation towards meiosis. Finally, this these showed that Fsh reduces Sertoli cell expression of Amh, and at the same time, stimulates Igf3, which promotes germ cell differentiation. Therefore, the main progress realized in this thesis is that the Fsh effects on spermatogenesisare shown to be mediated by growth factors, and not only by steroids, as it was believed previously. Moreover, there is very little knowledge in vertebrates in general about the local “translation” of the Fsh and Androgen signals into paracrine signals/cell-cell signals that modulate germ cell behaviour. Igf3, derived from a new paralogue of the igf1gene, seems to function via an evolutionary conserved insulin/Igf signaling mechanism, while the Amh effects on SSC behavior, described for the first time in fish, should be tested in mammals (or other tetrapods), as it might be a conserved but yet undetected effect.

  • Thyroid Hormone Stimulates the Proliferation of Sertoli Cells and Single Type A Spermatogonia in Adult Zebrafish (Danio rerio) Testis
    Endocrinology, 2013
    Co-Authors: R. D. V. S. Morais, Jan Bogerd, Rafael Henrique Nobrega, L. R. França, N. E. Gómez-gonzález, Ruben Schmidt, Rüdiger W. Schulz
    Abstract:

    Thyroid hormones participate in regulating growth and homeostatic processes in vertebrates, including development and adult functioning of the reproductive system. Here we report a new stimulatory role of thyroid hormone on the proliferation of Sertoli cells (SCs) and single, type A undifferentiated spermatogonia (A(und)) in adult zebrafish testes. A role for T3 in zebrafish testis is suggested by in situ hybridization studies, which localized thyroid receptor α (thrα) in SCs and the β (thrβ) mRNA in Sertoli and Leydig cells. Using a primary zebrafish testis tissue culture system, the effect of T3 on steroid Release, spermatogenesis, and the expression of selected genes was evaluated. Basal steroid Release and Leydig cell gene expression did not change in response to T3. However, in the presence of FSH, T3 potentiated gonadotropin-stimulated Androgen Release as well as Androgen receptor (ar) and 17α-hydroxylase/17,20 lyase (cyp17a1) gene expression. Moreover, T3 alone stimulated the proliferation of both SCs and A(und), potentially resulting in newly formed spermatogonial cysts. Additional tissue culture studies demonstrated that Igf3, a new, gonad-specific member of the IGF family, mediated the stimulatory effect of T3 on the proliferation of A(und) and SCs. Finally, T3 induced changes in connexin 43 mRNA levels in the testis, a known T3-responsive gene. Taken together, our studies suggest that T3 expands the population of SCs and A(und) involving Igf signaling and potentiates gonadotropin-stimulated testicular Androgen production as well as Androgen sensitivity.

  • studies in zebrafish reveal unusual cellular expression patterns of gonadotropin receptor messenger ribonucleic acids in the testis and unexpected functional differentiation of the gonadotropins
    Endocrinology, 2010
    Co-Authors: Angel Garcialopez, Geir Lasse Taranger, Paul P. De Waal, Hugo R De Jonge, Rafael Henrique Nobrega, Wytske Van Dijk, Wieger Hemrika, Jan Bogerd
    Abstract:

    This study aimed to improve, using the zebrafish model, our understanding of the distinct roles of pituitary gonadotropins FSH and LH in regulating testis functions in teleost fish. We report, for the first time in a vertebrate species, that zebrafish Leydig cells as well as Sertoli cells express the mRNAs for both gonadotropin receptors (fshr and lhcgr). Although Leydig cell fshr expression has been reported in other piscine species and may be a common feature of teleost fish, Sertoli cell lhcgr expression has not been reported previously and might be related to the undifferentiated gonochoristic mode of gonadal sex differentiation in zebrafish. Both recombinant zebrafish (rzf) gonadotropins (i.e. rzfLH and rzfFSH) stimulated Androgen Release in vitro and in vivo, with rzfFSH being significantly more potent than rzfLH. Forskolin-induced adenylate cyclase activation mimicked, whereas the protein kinase A inhibitor H-89 significantly reduced, the gonadotropin-stimulated Androgen Release. Therefore, we conclude that both FSH receptor and LH/choriogonadotropin receptor signaling are predominantly mediated through the cAMP/protein kinase A pathway to promote steroid production. Despite this similarity, other downstream mechanisms seem to differ. For example, rzfFSH up-regulated the testicular mRNA levels of a number of steroidogenesis-related genes both in vitro and in vivo, whereas rzfLH or human chorionic gonadotropin did not. Although not fully understood at present, these differences could explain the capacity of FSH to support both steroidogenesis and spermatogenesis on a long-term basis, whereas LH-stimulated steroidogenesis might be a more acute process, possibly restricted to periods during which peak steroid levels are required.

S S C Yen - One of the best experts on this subject based on the ideXlab platform.

  • sublingual administration of testosterone hydroxypropyl β cyclodextrin inclusion complex simulates episodic Androgen Release in hypogonadal men
    The Journal of Clinical Endocrinology and Metabolism, 1991
    Co-Authors: Cynthia A Stuenkel, R E Dudley, S S C Yen
    Abstract:

    In search of a more physiological testosterone (T) replacement therapy for hypogonadal states, we evaluated an inclusion complex of T with 2-hydroxypropyl-β-cyclodextrin (HPBCD). HPBCD enhances T solubility and absorption, but HPBCD is not absorbed. Five hypogonadal men (mean age, 32.4 ± 2.3 yr) with serum T levels below the normal range were treated in two separate experimental phases with either a 2.5- or 5.0-mg tablet of sublingual (SL) T-HPBCD three times daily for 7 days. Acute pharmacodynamic changes were monitored at baseline and 10, 20, and 40 min and 1, 1.5, 2, 3, 4, and 8 h after administration of the first dose. At the 5-mg dose, a maximal concentration (Cmax) of T (85.4 ± 11.0 nmol/L) was achieved in 20 min (63 ± 24-fold increase), followed by a rapid decline to below the normal range (<12 nmol/L) at 2 h, with an estimated half-life of decline of 1.87 ± 0.19 h. The dihydrotestosterone (DHT) Cmax (4.1 ± 0.5 nmol/L) occurred at 32 ± 5 min (8.9 ± 1.3-fold increase) and declined to below the norma...

  • Sublingual administration of testosterone-hydroxypropyl-β-cyclodextrin inclusion complex simulates episodic Androgen Release in hypogonadal men
    The Journal of clinical endocrinology and metabolism, 1991
    Co-Authors: Cynthia A Stuenkel, R E Dudley, S S C Yen
    Abstract:

    In search of a more physiological testosterone (T) replacement therapy for hypogonadal states, we evaluated an inclusion complex of T with 2-hydroxypropyl-β-cyclodextrin (HPBCD). HPBCD enhances T solubility and absorption, but HPBCD is not absorbed. Five hypogonadal men (mean age, 32.4 ± 2.3 yr) with serum T levels below the normal range were treated in two separate experimental phases with either a 2.5- or 5.0-mg tablet of sublingual (SL) T-HPBCD three times daily for 7 days. Acute pharmacodynamic changes were monitored at baseline and 10, 20, and 40 min and 1, 1.5, 2, 3, 4, and 8 h after administration of the first dose. At the 5-mg dose, a maximal concentration (Cmax) of T (85.4 ± 11.0 nmol/L) was achieved in 20 min (63 ± 24-fold increase), followed by a rapid decline to below the normal range (

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  • involvement of adenosine monophosphate activated kinase in interleukin 6 regulation of steroidogenic acute regulatory protein and cholesterol side chain cleavage enzyme in the bovine zona fasciculata and zona reticularis
    Steroids, 2018
    Co-Authors: Matharage S I De Silva, Adam Wesley Dayton, Lance R Rhoten, John W Mallett, Jared C Reese, Mathieu D Squires, James P. Porter, Andrew P Dalley, Allan M Judd
    Abstract:

    Abstract In bovine adrenal zona fasciculata (ZF) and NCI-H295R cells, interleukin-6 (IL-6) increases cortisol Release, increases expression of steroidogenic acute regulatory protein (StAR), cholesterol side chain cleavage enzyme (P450scc), and steroidogenic factor 1 (SF-1) (increases steroidogenic proteins), and decreases the expression of adrenal hypoplasia congenita-like protein (DAX-1) (inhibits steroidogenic proteins). In contrast, IL-6 decreases bovine adrenal zona reticularis (ZR) Androgen Release, StAR, P450scc, and SF-1 expression, and increases DAX-1 expression. Adenosine monophosphate (AMP) activated kinase (AMPK) regulates steroidogenesis, but its role in IL-6 regulation of adrenal steroidogenesis is unknown. In the present study, an AMPK activator (AICAR) increased ( P P P P P

  • Interleukin-6 inhibits adrenal Androgen Release from bovine adrenal zona reticularis cells by inhibiting the expression of steroidogenic proteins
    Domestic animal endocrinology, 2015
    Co-Authors: S. Mcilmoil, Gerald B. Call, Michelle Barney, Janae Strickland, Allan M Judd
    Abstract:

    Abstract Interleukin-6 (IL-6) is secreted by adrenocortical cells and modifies cortisol secretion. In this study, the effects of IL-6 on adrenal Androgen Release were investigated. The zona reticularis (ZR) was generally isolated from bovine adrenal glands by dissection. In select experiments, the intact adrenal cortex (ie, all 3 adrenocortical zones) was dissected from the adrenal glands. For Androgen Release experiments, ZR and intact adrenocortical cubes were dispersed into isolated cells, the cells cultured and exposed to IL-6 and/or adrenocorticotropic hormone (ACTH), and Androgen Release determined by radioimmunoassay. Basal and ACTH-stimulated Androgen Release from the ZR was inhibited by IL-6 in a concentration-dependent (10–1000 pg/mL) and time-dependent (4–24 h) manner ( P P P P

  • Leukemia inhibitory factor protein and receptors are expressed in the bovine adrenal cortex and increase cortisol and decrease adrenal Androgen Release.
    Domestic animal endocrinology, 2008
    Co-Authors: Alison M. Woods, James P. Porter, Christopher J. Mcilmoil, Ernestina N. Rankin, Alissa A. Packer, Jessica C. Stevens, Jeffrey A. Macievic, Aaron B. Brown, Allan M Judd
    Abstract:

    The Release of adrenal steroids during acute stress is primarily regulated by adrenocorticotropic hormone (ACTH). In contrast, during chronic inflammatory stress additional factors are involved in regulating adrenal function. Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that increases ACTH Release from the pituitary. In addition, LIF and LIF receptors (LIFR) are expressed in the human adrenal cortex and the human adrenocortical tumor cell line H295R. Furthermore, LIF increases basal and ACTH-stimulated cortisol Release from H295R cells. However, the expression of LIF and LIFR in non-human adrenal glands and the effects of LIF on the Release of cortisol from adrenal cells of non-human species have not been determined. Furthermore, the effects of LIF on adrenal Androgen Release from all species are unknown. In this study, immunohistochemistry, Western blots, RT-PCR, and nucleotide sequencing was utilized to demonstrate that LIF and its receptor are expressed throughout the bovine adrenal cortex. Although LIF did not modify basal cortisol Release from dispersed cells isolated from the bovine adrenal zona fasciculate, this cytokine increased ACTH-stimulated Release of cortisol from these cells in a manner dependent on the LIF concentration and exposure interval. In contrast, LIF in a concentration-dependent and time-dependent manner decreased basal and ACTH-stimulated adrenal Androgen Release from dispersed cells isolated from the bovine adrenal zona reticularis. Because LIF Release increases during inflammatory stress and this cytokine stimulates adrenal cortisol Release and inhibits adrenal Androgen Release, this cytokine may play an important role in regulating the Release of adrenal steroids during inflammatory stress.

  • Interleukin-4 increases cortisol Release and decreases adrenal Androgen Release from bovine adrenal cells.
    Domestic animal endocrinology, 2007
    Co-Authors: Alison M. Woods, Allan M Judd
    Abstract:

    ACTH is the primary regulator of adrenal function during acute stress. However, during chronic inflammatory stress additional factors play a major role in the regulation of adrenal secretion. Many cytokines circulate in the blood and are synthesized and Released from adrenal tissue. Furthermore, these peptides modify adrenal function. Recently, interleukin-4 (IL-4) was demonstrated to be Released from a human adrenal tumor cell line. Therefore, we hypothesized that normal bovine adrenocortical cells could express IL-4 and that this cytokine may modify adrenal function. We determined that IL-4 and IL-4 receptors (IL-4R) are expressed in the bovine adrenal cortex whereas the expression of IL-4 and IL-4R in the adrenal medulla was not apparent. Exposure of dispersed bovine adrenocortical cells isolated from the zona fasciculate to IL-4 did not modify basal Release of cortisol. However, the ACTH-stimulated Release of cortisol from the bovine adrenal cells was augmented by IL-4. IL-4 exposure had no affect on adrenal Androgen Release from bovine zona reticularis cells, but IL-4 inhibited the ACTH-stimulated Release of adrenal Androgens from these cells. The effects of IL-4 on ACTH-stimulated cortisol and adrenal Androgen Release were dependent upon the IL-4 incubation interval and the IL-4 concentration. Because communication between the immune and endocrine systems is important in inflammatory conditions, IL-4 may play a role in coordinating the adrenal response to inflammatory stress.