J. Bogerd

Hebrew University of Jerusalem, Jerusalem, Jerusalem District, Israel

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Publications (125)171.71 Total impact

  • Source
    Article: Perspectives on fish gonadotropins and their receptors.
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    ABSTRACT: Teleosts lack a hypophyseal portal system and hence neurohormones are carried by nerve fibers from the preoptic region to the pituitary. The various cell types in the teleost pituitary are organized in discrete domains. Fish possess two gonadotropins (GtH) similar to FSH and LH in other vertebrates; they are heterodimeric hormones that consist of a common alpha subunit non-covalently associated with a hormone-specific beta subunit. In recent years the availability of molecular cloning techniques allowed the isolation of the genes coding for the GtH subunits in 56 fish species representing at least 14 teleost orders. Advanced molecular engineering provides the technology to produce recombinant GtHs from isolated cDNAs. Various expression systems have been used for the production of recombinant proteins. Recombinant fish GtHs were produced for carp, seabream, channel and African catfish, goldfish, eel, tilapia, zebrafish, Manchurian trout and Orange-spotted grouper. The hypothalamus in fishes exerts its regulation on the release of the GtHs via several neurohormones such as GnRH, dopamine, GABA, PACAP, IGF-I, norepinephrine, NPY, kisspeptin, leptin and ghrelin. In addition, gonadal steroids and peptides exert their effects on the gonadotropins either directly or via the hypothalamus. All these are discussed in detail in this review. In mammals, the biological activities of FSH and LH are directed to different gonadal target cells through the cell-specific expression of the FSH receptor (FSHR) and LH receptor (LHR), respectively, and the interaction between each gonadotropin-receptor couple is highly selective. In contrast, the bioactivity of fish gonadotropins seems to be less specific as a result of promiscuous hormone-receptor interactions, while FSHR expression in Leydig cells explains the strong steroidogenic activity of FSH in certain fish species.
    General and Comparative Endocrinology 09/2009; 165(3):412-37. · 3.27 Impact Factor
  • Article: Leydig Cells Express Follicle-Stimulating Hormone Receptors in African Catfish
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    ABSTRACT: This report aimed to establish, using African catfish, Clarias gariepinus, as model species, a basis for understanding a well-known, although not yet clarified, feature of male fish reproductive physiology: the strong steroidogenic activity of FSHs. Assays with gonadotropin receptor-expressing cell lines showed that FSH activated its cognate receptor (FSHR) with an at least 1000-fold lower EC50 than when challenging the LH receptor (LHR), whereas LH stimulated both receptors with similar EC(50)s. In androgen release bioassays, FSH elicited a significant response at lower concentrations than those required to cross-activate of the LHR, indicating that FSH stimulated steroid release via FSHR-dependent mechanisms. LHR/FSHR-mediated stimulation of androgen release was completely abolished by H-89, a specific protein kinase A inhibitor, pointing to the cAMP/protein kinase A pathway as the main route for both LH- and FSH-stimulated steroid release. Localization studies showed that intratubular Sertoli cells express FSHR mRNA, whereas, as reported for the first time in a vertebrate, catfish Leydig cells express both LHR and FSHR mRNA. Testicular FSHR and LHR mRNA expression increased gradually during pubertal development. FSHR, but not LHR, transcript levels continued to rise between completion of the first wave of spermatogenesis at about 7 months and full maturity at about 12 months of age, which was associated with a previously recorded approximately 3-fold increase in the steroid production capacity per unit testis weight. Taken together, our data strongly suggest that the steroidogenic potency of FSH can be explained by its direct trophic action on FSHR-expressing Leydig cells. (Endocrinology 150: 357-365, 2009)
    Endocrinology 01/2009; 150(1):357-365. · 4.46 Impact Factor
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    Article: Phosphoprotein enriched in astrocytes-15 is expressed in mouse testis and protects spermatocytes from apoptosis.
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    ABSTRACT: Phosphoprotein enriched in astrocytes (PEA-15) is a 15 kDa acidic serine-phosphorylated protein expressed in different cell types, especially in the CN. We initially detected the expression of PEA-15 in primary cultures of Sertoli cells. To assess the presence and localization of PEA-15 in the mouse testis, we studied the expression pattern of the PEA-15 protein by immunohistochemistry and mRNA by in situ hybridization. Both the protein and the mRNA of PEA-15 were localized in the cytoplasm of Sertoli cells, all types of spermatogonia, and spermatocytes up till zygotene phase of the meiotic prophase. Subsequently, with ongoing development of the spermatocytes, the expression decreased and was very low in the cytoplasm of diplotene spermatocytes. To analyze the possible role of PEA-15 in the developing testis, null mutants for PEA-15 were examined. As the PEA-15 C terminus contains residues for ERK binding, we studied possible differences between the localization of the ERK2 protein in wild type (WT) and PEA-15(-/-)mice. In the WT testis, ERK2 was localized in the cytoplasm of Sertoli cells, B spermatogonia, preleptotene, leptotene, and zygotene spermatocytes, whereas in the KO testis, ERK2 was primarily localized in the nuclei of these cells and only little staining remained in the cytoplasm. Moreover, in PEA-15-deficient mice, significantly increased numbers of apoptotic spermatocytes were found, indicating an anti-apoptotic role of PEA-15 during the meiotic prophase. The increased numbers of apoptotic spermatocytes were not found at a specific step in the meiotic prophase.
    Reproduction (Cambridge, England) 05/2007; 133(4):743-51. · 3.09 Impact Factor
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    Article: Expression of stress inducible protein 1 (Stip1) in the mouse testis.
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    ABSTRACT: Phthalate esters are considered endocrine disruptors that interfere with the endocrine balance and development of the mammalian testis. Mono-2-ethylhexyl phthalate (MEHP), the active metabolite of the ubiquitously used plasticizer di-2-ethylhexyl phthalate (DEHP), acts upon Sertoli cells as initial target. By subtractive cDNA libraries we identified genes deregulated as response to MEHP in primary cultures of mouse Sertoli cells. The expression of mouse stress inducible protein 1 (Stip1) was detected as upregulated as a result of MEHP exposure. Stip1 is a cochaperone protein that is homologous to the human heat shock cognate protein 70 (hsc70)/heat shock protein 90 (hsp90)-organizing protein (Hop). To assess the presence and localization of Stip1 in mouse testis and its potential role in stress defense, we studied the expression pattern of the Stip1 protein by immunohistochemistry and of the mRNA by in situ hybridization. Both the protein and the mRNA of Stip1 were mainly found in the cytoplasm of all types of spermatogonia and spermatocytes up till zygotene, the expression decreased during late pachytene and was very weak in diplotene spermatocytes and round spermatids. Interestingly, this expression pattern resembled the pattern of stress sensitivity of spermatogenic cells in that the most sensitive cell types show the weakest expression of Stip1. This suggests an important role for Stip1 in the ability of germ cells to survive in stress conditions including high temperatures.
    Molecular Reproduction and Development 12/2006; 73(11):1361-6. · 2.53 Impact Factor
  • Article: Expression of stress inducible protein 1 (Stip1) in the mouse testis
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    ABSTRACT: Phthalate esters are considered endocrine disruptors that interfere with the endocrine balance and development of the mammalian testis. Mono-2-ethylhexyl phthalate (MEHP), the active metabolite of the ubiquitously used plasticizer di-2-ethylhexyl phthalate (DEHP), acts upon Sertoli cells as initial target. By subtractive cDNA libraries we identified genes deregulated as response to MEHP in primary cultures of mouse Sertoli cells. The expression of mouse stress inducible protein 1 (Stip1) was detected as upregulated as a result of MEHP exposure. Stip1 is a cochaperone protein that is homologous to the human heat shock cognate protein 70 (hsc70)/heat shock protein 90 (hsp90)—organizing protein (Hop). To assess the presence and localization of Stip1 in mouse testis and its potential role in stress defense, we studied the expression pattern of the Stip1 protein by immunohistochemistry and of the mRNA by in situ hybridization. Both the protein and the mRNA of Stip1 were mainly found in the cytoplasm of all types of spermatogonia and spermatocytes up till zygotene, the expression decreased during late pachytene and was very weak in diplotene spermatocytes and round spermatids. Interestingly, this expression pattern resembled the pattern of stress sensitivity of spermatogenic cells in that the most sensitive cell types show the weakest expression of Stip1. This suggests an important role for Stip1 in the ability of germ cells to survive in stress conditions including high temperatures. Mol. Reprod. Dev. 73: 1361–1366, 2006. © 2006 Wiley-Liss, Inc.
    Molecular Reproduction and Development 10/2006; 73(11):1361 - 1366. · 2.53 Impact Factor
  • Article: Developmental regulation of homeobox gene expression in dorsal root ganglion neurons is not recapitulated during regeneration of the crushed sciatic nerve.
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    ABSTRACT: The adult peripheral nervous system is able to regenerate after injury. Regeneration is associated with the expression of new genes and proteins. Proteins abundant in developing axons increase in expression after injury, whereas proteins involved in neurotransmission are downregulated. It has been hypothesized that molecular mechanisms underlying regeneration-associated alterations in gene expression may be a recapitulation of developmental processes. These gene expression changes are likely to be regulated by changes in the gene expression of transcription factors. As homeobox genes play important roles in embryonic development of the nervous system, it makes them candidates for a regulatory role in the process of regeneration. Here we show that the relative mRNA expression levels of Isl1 decreased shortly after crush, but those of DRG11, Lmx1b, and Pax3 did not change after crush. These data indicate that the developmental expression patterns of the homeobox genes studied here are not recapitulated during regeneration of the dorsal root ganglia neurons. We conclude that developmental gene expression programs controlled by these homeobox genes are not directly involved in sciatic nerve regeneration.
    Neuroscience 02/2004; 125(3):645-50. · 3.38 Impact Factor
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    Article: Both recombinant African catfish LH and FSH are able to activate the African catfish FSH receptor.
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    ABSTRACT: LH and FSH are heterodimeric glycoprotein hormones, composed of a common alpha-subunit non-covalently associated with a hormone-specific beta-subunit. Repeated efforts to isolate catfish FSH (cfFSH) have not been successful and only catfish LH (cfLH) has been purified from catfish pituitaries. Recently, however, we succeeded in cloning the cDNA encoding the putative cfFSHbeta; the cDNAs for the alpha- and beta-subunit of cfLH have been cloned before. Here we report the expression of biologically active cfLH and cfFSH in the soil amoeba, Dictyostelium discoideum. The biological activity of the recombinant hormones was analyzed using cell lines transiently expressing either the cfLH receptor or the cfFSH receptor. Moreover, a primary testis tIssue culture system served to study the steroidogenic potency of the recombinant hormones. Our results demonstrated that Dictyostelium produced biologically active, recombinant catfish gonadotropins, with recombinant cfLH being almost indistinguishable from its native counterpart, purified from pituitaries. Although recombinant cfFSH has significant effects in the bioassays used in this study, the specific function of native cfFSH in the control of reproduction and its expression patterns are not yet understood.
    Journal of Molecular Endocrinology 09/2003; 31(1):133-40. · 3.48 Impact Factor
  • Article: Cloning and spatiotemporal expression of the follicle-stimulating hormone beta subunit complementary DNA in the African catfish (Clarias gariepinus).
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    ABSTRACT: The gene and cDNA encoding a putative follicle-stimulating hormone beta subunit (cfFSHbeta) from African catfish (Clarias gariepinus) were cloned. Similar to other FSHbeta genes, the cfFSHbeta gene consisted of three exons interrupted by two introns. The cfFSHbeta cDNA coded for a mature protein of 115 amino acids. The 12 cysteines that are required for the typical tertiary folding of glycoprotein hormone beta subunits were positionally conserved in cfFSHbeta. The cfFSHbeta mRNA expression was exclusively detected in the pituitary and was detectable before pubertal development was initiated. The cfFSHbeta transcript levels increased in particular during early stages of puberty and reached constantly high levels after the first appearance of spermatids in the testis. The cfFSHbeta mRNA-positive cells were localized in the proximal pars distalis. Castration of mature males caused elevated cfFSHbeta mRNA levels that were decreased by steroid replacement. Previous work indicated that the African catfish is an interesting model to study the regulation of gonadal functions because cfLH is able to activate both the catfish luteinizing hormone receptor (cfLH-R) and follicle-stimulating hormone receptor (cfFSH-R). Because cfFSH purification has failed so far, ongoing studies are directed toward the production of recombinant cfFSH. After all, the developmental and hormonal regulation of cfFSHbeta transcript levels opens the possibility for physiologically relevant actions of the putative cfFSH, next to the presumptive bifunctionally acting cfLH.
    Biology of Reproduction 05/2003; 68(4):1324-32. · 4.01 Impact Factor
  • Article: Cloning and expression of a functional estrogen receptor-alpha from African catfish (Clarias gariepinus) pituitary.
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    ABSTRACT: An African catfish (Clarias gariepinus) estrogen receptor-alpha (cfERalpha) cDNA fragment was amplified by RT-PCR, in combination with a modified 3'-RACE procedure, on total RNA extracted from pituitary. This cDNA fragment was used to screen an African catfish pituitary cDNA library. A clone was obtained that contained an open-reading frame coding for a 620 amino acid cfERalpha protein with a deduced molecular mass of 68.1 kDa. In addition, a partial African catfish estrogen receptor-beta (cfERbeta) cDNA fragment was amplified by RT-PCR on total RNA extracted from testis. Neighbor-joining analysis was used to infer a phylogenetic classification for cfERalpha and cfERbeta. The tree obtained indicated that there are two major clusters of vertebrate ERs: ERalpha and ERbeta. Within each cluster, teleost and tetrapod ER sister clades could be distinguished. The cfERalpha clustered with other teleost ERalphas, whereas cfERbeta clustered with other teleost ERbetas. The ligand-induced transcriptional activity of cfERalpha was demonstrated in a transient gene expression assay using cells in which an acute estrogenic response was created by co-transfecting cultures with recombinant cfERalpha cDNA expression vector constructs in the presence of an estrogen-dependent reporter plasmid. Real-time, quantitative PCR revealed that cfERalpha transcripts were most abundantly expressed in pituitary, while in all other tIssues tested the relative cfERalpha mRNA levels were less than approximately 5% of the level obtained in pituitary. Moreover, we found that, during pubertal development, the relative cfERalpha mRNA levels gradually increased in African catfish pituitary.
    Journal of Molecular Endocrinology 05/2003; 30(2):173-85. · 3.48 Impact Factor
  • Article: Cloning and functional characterization of a testicular TSH receptor cDNA from the African catfish (Clarias gariepinus).
    H F Vischer, J Bogerd
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    ABSTRACT: A cDNA encoding a putative thyroid-stimulating hormone receptor (cfTSH-R) was cloned from the testis of the African catfish (Clarias gariepinus). The cfTSH-R showed the highest amino acid sequence identity with the TSH-Rs of other fish species. In addition, an insertion of approximately 50 amino acids, specific for the TSH-R subfamily, was also present in the carboxy terminus of the amino-terminal extracellular domain of the cfTSH-R. Next to the testis and thyroid follicles, abundant cfTSH-R expression was detected in cerebellum, brain, ovary, seminal vesicles and pituitary, while weaker expression was found in muscle, stomach, intestine, head-kidney, liver, kidney and heart. HEK-T 293 cells, transiently expressing the cfTSH-R, significantly increased intracellular cAMP levels in response to human TSH. Catfish LH, human choriogonadotropin and human FSH were also able to induce this cfTSH-R-mediated response, although with considerably lower efficiency than human TSH. These results indicated that a functional cfTSH-R had been cloned from the testis of African catfish.
    Journal of Molecular Endocrinology 05/2003; 30(2):227-38. · 3.48 Impact Factor
  • Article: Cloning and functional characterization of a gonadal luteinizing hormone receptor complementary DNA from the African catfish (Clarias gariepinus).
    H F Vischer, J Bogerd
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    ABSTRACT: A cDNA encoding a putative African catfish (Clarias gariepinus) gonadal LH receptor (cfLH-R) has been cloned. Multiple sequence alignment of the deduced amino acid sequence revealed that the cfLH-R had the highest identity with vertebrate LH receptors (>50%). Overall sequence identity between the cfLH-R and the African catfish FSH receptor (cfFSH-R) is 47%. Sequence analysis of part of the cfLH-R gene revealed the presence of an intron typically found in other vertebrate LH-R genes. Abundant cfLH-R mRNA expression was detected in ovary and testis as well as in head-kidney (the adrenal homologue in fish). Other tissues, such as muscle, brain, cerebellum, stomach, heart, and seminal vesicles, also contained detectable cfLH-R mRNA. Transient expression of the cfLH-R in HEK-T 293 cells resulted in significantly increased basal cAMP levels in the absence of gonadotropic hormone. The cAMP levels could be further elevated in response to catfish LH, salmon LH, human LH, human choriogonadotropin, and human FSH. Salmon FSH and human TSH, however, were inactive. We conclude that we have cloned a cDNA encoding the LH-R of the African catfish. This receptor displays constitutive activity but is still responsive to additional ligand-induced activation.
    Biology of Reproduction 01/2003; 68(1):262-71. · 4.01 Impact Factor
  • Article: Sex steroids and their involvement in the cortisol-induced inhibition of pubertal development in male common carp, Cyprinus carpio L.
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    ABSTRACT: The onset and regulation of puberty is determined by functional development of the brain-pituitary-gonad (BPG) axis. Sex steroids produced in the gonads play an important role in the onset of puberty. Stress interferes with reproduction and the functioning of the BPG axis, and cortisol has frequently been indicated as a major factor mediating the suppressive effect of stress on reproduction. Prolonged elevated cortisol levels, implicated in stress adaptation, inhibited pubertal development in male common carp (Cyprinus carpio). Cortisol treatment caused a retardation of pubertal testis development and reduced the LH pituitary content and the salmon GnRHa-stimulated LH secretion in vitro. A reduced synthesis of androgens also was observed. These findings suggest that the cortisol-induced inhibition of testicular development and the maturation of pituitary gonadotrophs are mediated by an effect on testicular androgen secretion. In this study, we combined cortisol treatment with a replacement of the testicular steroid hormones (testosterone and 11-oxygenated androgens) to investigate the role of these steroids in the cortisol-induced suppression of pubertal development. The effect of cortisol on spermatogenesis was independent of 11-ketotestosterone, whereas the effect on the pituitary was an indirect one, involving the testicular secretion of testosterone.
    Biology of Reproduction 09/2002; 67(2):465-72. · 4.01 Impact Factor
  • Article: Differences in structure-function relations between nonmammalian GnRH receptors: what we have learnt from the African catfish GnRH receptor.
    Progress in brain research 02/2002; · 3.04 Impact Factor
  • Article: Testosterone inhibits 11-ketotestosterone-induced spermatogenesis in African catfish (Clarias gariepinus).
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    ABSTRACT: Male fish produce 11-ketotestosterone as a potent androgen in addition to testosterone. Previous experiments with juvenile African catfish (Clarias gariepinus) showed that 11-ketotestosterone, but not testosterone, stimulated spermatogenesis, whereas testosterone, but not 11-ketotestosterone, accelerated pituitary gonadotroph development. Here, we investigated the effects of combined treatment with these two types of androgens on pituitary gonadotroph and testis development. Immature fish were implanted for 2 wk with silastic pellets containing 11-ketotestosterone, testosterone, 5alpha-dihydrotestosterone, or estradiol-17beta; cotreatment groups received 11-ketotestosterone in combination with one of the other steroids. Testicular weight and pituitary LH content were higher (two- and fivefold, respectively) in the end control than in the start control group, reflecting the beginning of normal pubertal development. Treatment with testosterone or estradiol-17beta further increased the pituitary LH content four- to sixfold above the end control levels. This stimulatory effect on the pituitary LH content was not modulated by cotreatment with 11-ketotestosterone. However, the stimulatory effect of 11-ketotestosterone on testis growth and spermatogenesis was abolished by cotreatment with testosterone, but not by cotreatment with estradiol-17beta or 5alpha-dihydrotestosterone. Also, normal pubertal testis development was inhibited by prolonged (4 wk) treatment with testosterone. The inhibitory effect of testosterone may involve feedback effects on pituitary FSH and/or on FSH receptors in the testis. It appears that the balanced production of two types of androgens, and the control of their biological activities, are critical to the regulation of pubertal development in male African catfish.
    Biology of Reproduction 01/2002; 65(6):1807-12. · 4.01 Impact Factor
  • Article: Inhibitory activity of alternative splice variants of the bullfrog GnRH receptor-3 on wild-type receptor signaling.
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    ABSTRACT: Recently we characterized three distinct GnRH receptors in the bullfrog (bfGnRHR-1, bfGnRHR-2, and bfGnRHR-3). In the present study, we further investigated the expression and function of splice variants, generated from the primary bfGnRHR-3 transcript by exon skipping (splice variant 1), intron retention (splice variants 2 and 3), and/or transcriptional slippage (splice variant 4), apart from the constitutively spliced form (wild-type). Cellular expression and function of the splice variants were examined using a transient expression system. Immunoblot analysis revealed that the wild-type receptor and all splice variant proteins were expressed in transfected HeLa cells with no significant differences in expression levels. These splice variants showed a very low binding affinity to ligand and did not induce signal transduction in response to GnRH treatment. Interestingly, cotransfection of the wild-type with splice variants 2--4, but not with splice variant 1, significantly inhibited wild-type receptor-mediated signaling. Subcellular localization analysis of green fluorescent protein-tagged wild-type and splice variant proteins revealed that the wild-type receptor protein was mainly localized in the cell membrane, whereas the splice variant 1 protein was exclusively detected in the cytoplasm. The splice variant 2--4 proteins, however, were found in both the cell membrane and cytoplasm. The inhibition of wild-type receptor signaling by splice variants 2--4 and the subcellular localization of splice variants 2-4 suggest a possible physical interaction of splice variants 2--4 with the wild-type receptor protein. In addition, the ratio of mRNA levels of the wild-type to splice variants 2--4 significantly varied from hibernation (wild-type < splice variants 2--4) to the prebreeding season (wild-type > splice variants 2--4). Collectively, these results suggest that alternative splicing of the bfGnRHR-3 primary transcript plays a role in fine-tuning GnRH receptor function in amphibians.
    Endocrinology 10/2001; 142(9):4015-25. · 4.46 Impact Factor
  • Article: Development of three distinct GnRH neuron populations expressing two different GnRH forms in the brain of the African catfish (Clarias gariepinus).
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    ABSTRACT: The early development of both the catfish gonadotropin-releasing hormone (cfGnRH)- and the chicken GnRH-II (cGnRH-II) system was investigated in African catfish by immunocytochemistry by using antibodies against the GnRH-associated peptide (GAP) of the respective preprohormones. Weakly cfGnRH-immunoreactive (ir) neurons and fibers were present at 2 weeks after hatching (ph) but only in the ventral telencephalon and pituitary. Two weeks later, cfGnRH fibers and neurons were also observed in more rostral and in more caudal brain areas, mainly in the preoptic area and hypothalamus. Based on differences in temporal, spatial, and morphologic appearance, two distinct cfGnRH populations were identified in the ventral forebrain: a population innervating the pituitary (ventral forebrain system) and a so-called terminal nerve (TN) population. DiI tracing studies revealed that the TN population has no neuronal connections with the pituitary. The cGnRH-II system is present from 2 weeks ph onward in the midbrain tegmentum and only their size and staining intensity increased during development. Based on the comparison of GnRH systems amongst vertebrates, we hypothesize that during fish evolution, three different GnRH systems evolved, each expressing their own molecular form: the cGnRH-II system in the midbrain, a hypophysiotropic GnRH system in the hypothalamus with a species-specific GnRH form, and a salmon GnRH-expressing TN population. This hypothesis is supported by phylogenetic analysis of known GnRH precursor amino acid sequences. We hypothesize, because the African catfish is a less advanced teleost species, that it contains the cfGnRH form both in the ventral forebrain system and in the TN population.
    The Journal of Comparative Neurology 09/2001; 437(3):308-20. · 3.81 Impact Factor
  • Article: Proper receptor signalling in a mutant catfish gonadotropin-releasing hormone receptor lacking the highly conserved Asp(90) residue.
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    ABSTRACT: The negatively charged side chain of an Asp residue in transmembrane domain 2 is likely to play an important role in receptor signalling since it is highly conserved in the whole family of G protein-coupled receptors, except in mammalian gonadotropin-releasing hormone (GnRH) receptors. In this paper we show that the conserved Asp(90) of the catfish GnRH receptor can be substituted by a neutral Asn(90) without abolishing receptor signalling if another negatively charged Glu(93) is introduced in a proximal region of the receptor interior, thereby mimicking the Glu(90)-Lys(121) salt bridge of mammalian GnRH receptors.
    FEBS Letters 08/2001; 501(2-3):131-4. · 3.54 Impact Factor
  • Article: Discrepancy between molecular structure and ligand selectivity of a testicular follicle-stimulating hormone receptor of the African catfish (Clarias gariepinus).
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    ABSTRACT: A putative FSH receptor (FSH-R) cDNA was cloned from African catfish testis. Alignment of the deduced amino acid sequence with other (putative) glycoprotein hormone receptors and analysis of the African catfish gene indicated that the cloned receptor belonged to the FSH receptor subfamily. Catfish FSH-R (cfFSH-R) mRNA expression was observed in testis and ovary; abundant mRNA expression was also detected in seminal vesicles. The isolated cDNA encoded a functional receptor since its transient expression in human embryonic kidney (HEK-T) 293 cells resulted in ligand-dependent cAMP production. Remarkably, African catfish LH (cfLH; the catfish FSH-like gonadotropin has not been purified yet) had the highest potency in this system. From the other ligands tested, only human recombinant FSH (hrFSH) was active, showing a fourfold lower potency than cfLH, while hCG and human TSH (hTSH) were inactive. Human CG (as well as cfLH, hrFSH, eCG, but not hTSH) stimulated testicular androgen secretion in vitro but seemed to be unable to bind to the cfFSH-R. However, it was known that hCG is biologically active in African catfish (e.g., induction of ovulation). This indicated that an LH receptor is also expressed in African catfish testis. We conclude that we have cloned a cDNA encoding a functional FSH-R from African catfish testis. The cfFSH-R appears to be less discriminatory for its species-specific LH than its avian and mammalian counterparts.
    Biology of Reproduction 07/2001; 64(6):1633-43. · 4.01 Impact Factor
  • Article: Gonadotropins, their receptors, and the regulation of testicular functions in fish.
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    ABSTRACT: The pituitary gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) regulate steroidogenesis and spermatogenesis by activating receptors expressed by Leydig cells (LH receptor) and Sertoli cells (FSH receptor), respectively. This concept is also valid in fish, although the piscine receptors may be less discriminatory than their mammalian counterparts. The main biological activity of LH is to regulate Leydig-cell steroid production. Steroidogenesis is moreover modulated in an autoregulatory manner by androgens. The male sex steroids (testosterone in higher vertebrates, 11-ketotestosterone in fish) are required for spermatogenesis, but their mode of action has remained obscure. While piscine FSH also appears to have steroidogenic activity, specific roles have not been described yet in the testis. The feedback of androgens on gonadotrophs presents a complex pattern. Aromatizable androgens/estrogens stimulate LH synthesis in juvenile fish; this effect fades out during maturation. This positive feedback on LH synthesis is balanced by a negative feedback on LH release, which may involve GnRH neurones. While the role of GnRH as LH secretagogue is evident, we have found no indication in adult male African catfish for a direct, GnRH-mediated stimulation of LH synthesis. The limited available information at present precludes a generalized view on the testicular feedback on FSH.
    Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology 07/2001; 129(2-3):407-17. · 1.92 Impact Factor
  • Article: Long-term cortisol treatment inhibits pubertal development in male common carp, Cyprinus carpio L.
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    ABSTRACT: The onset and regulation of puberty is determined by functional development of the brain-pituitary-gonad (BPG) axis. Stress has been shown to interfere with reproduction and the functioning of the BPG axis. The response to chronic and severe stress may require much energy and force the organism to make adaptive choices. Energy that is normally available for processes like growth, immune response, or reproduction will be channeled into restoration of the disturbed homeostasis. Cortisol plays a key role in the homeostatic adaptation during or after stress. In the present study, immature common carp were fed with cortisol-containing food pellets covering the pubertal period. We showed that cortisol caused an inhibition of pubertal development, by affecting directly or indirectly all components of the BPG axis. The salmon GnRH content of the brain was decreased. Luteinizing hormone- and FSH-encoding mRNA levels in the pituitary and LH plasma levels were diminished by long-term cortisol treatment, as was the testicular androgen secretion. Testicular development, reflected by gonadosomatic index and the first wave of spermatogenesis, was retarded.
    Biology of Reproduction 05/2001; 64(4):1063-71. · 4.01 Impact Factor

Institutions

  • 2009
    • Hebrew University of Jerusalem
      • Department of Animal Sciences
      Jerusalem, Jerusalem District, Israel
  • 1992–2009
    • Universiteit Utrecht
      • • Division of Endocrinology and Metabolism
      • • Division of Cell Biology
      • • Division of Experimental Psychology
      • • Division of Developmental Biology
      • • Institute of Biomembranes
      Utrecht, Provincie Utrecht, Netherlands
    • Kitasato University
      • Graduate School of Fisheries Sciences
      Tokyo, Tokyo-to, Japan
  • 2001
    • Chonnam National University
      • Department of Biology
      Yeoju, Gyeonggi, South Korea
  • 1999
    • French National Centre for Scientific Research
      Lyon, Rhone-Alpes, France
  • 1995
    • Austin College
      Austin, TX, USA
  • 1991–1993
    • VU University Amsterdam
      • Graduate School Neurosciences Amsterdam
      Amsterdam, North Holland, Netherlands