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  • 1
    In: Endocrinology, The Endocrine Society, Vol. 155, No. 5 ( 2014-05-01), p. 1874-1886
    Type of Medium: Online Resource
    ISSN: 0013-7227 , 1945-7170
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2014
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  • 2
    Online Resource
    Online Resource
    The Endocrine Society ; 2005
    In:  Endocrinology Vol. 146, No. 3 ( 2005-03), p. 1048-1052
    In: Endocrinology, The Endocrine Society, Vol. 146, No. 3 ( 2005-03), p. 1048-1052
    Type of Medium: Online Resource
    ISSN: 0013-7227 , 1945-7170
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2005
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  • 3
    Online Resource
    Online Resource
    The Endocrine Society ; 2011
    In:  Endocrinology Vol. 152, No. 1 ( 2011-01-01), p. 281-290
    In: Endocrinology, The Endocrine Society, Vol. 152, No. 1 ( 2011-01-01), p. 281-290
    Abstract: Social position in a dominance hierarchy is often tightly coupled with fertility. Consequently, an animal that can recognize and rapidly take advantage of an opportunity to rise in rank will have a reproductive advantage. Reproduction in all vertebrates is controlled by the brain-pituitary-gonad axis, and in males of the African cichlid fish Astatotilapia burtoni, GnRH1 neurons at the apex of this axis are under social control. However, little is known about how quickly social information is transformed into functional reproductive change, or about how socially controlled changes in GnRH1 neurons influence downstream actions of the brain-pituitary-gonad axis. We created an opportunity for reproductively suppressed males to ascend in status and then measured how quickly the perception of this opportunity caused changes in mRNA and protein levels of the pituitary gonadotropins. mRNA levels of the β-subunits of LH and FSH rose rapidly in the pituitary 30 min after suppressed males perceived an opportunity to ascend. In contrast, mRNA levels of GnRH receptor-1 remained unchanged during social transition but were higher in stable dominant compared with subordinate males. In the circulation, levels of both LH and FSH were also quickly elevated. There was a positive correlation between mRNA in the pituitary and circulating protein levels for LH and FSH, and both gonadotropins were positively correlated with plasma 11-ketotestosterone. Our results show that the pituitary is stimulated extremely rapidly after perception of social opportunity, probably to allow suppressed males to quickly achieve reproductive success in a dynamic social environment.
    Type of Medium: Online Resource
    ISSN: 0013-7227 , 1945-7170
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2011
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  • 4
    Online Resource
    Online Resource
    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A553-A554
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A553-A554
    Abstract: Somatostatin (SST) is a 14-amino acid peptide produced in the hypothalamus of vertebrates, including fish. It regulates many physiological processes such as growth development and metabolic processes in the animal’s body. Negative control of growth hormone in vivo and in vitro was characterized in several fish species such as salmon, goldfish, rainbow trout and tilapia. Although very important, the SST/SST-R system in Nile tilapia (Oreochromis niloticus) was not deeply characterized. The somatostatin system in tilapia possess two ligands (Somatostatin1b and Somatostatin 2), and five receptors (SST-R 1-5). Unlike mammals, in fish, FSH and LH are secreted from different cell populations in the pituitary. By performing cell specific transcriptome analysis of double-labelled transgenic tilapia expressing GFP and RFP in LH or FSH cells, respectively, we identified genes specifically enriched in each cell type. Analysis of the RNA-seq discovered 4 types of SST-Rs: sstr2, sstr3, sstr5 and sstr5x3. The specific localization of each SST-R was identified by In Situ hybridization with specific probes for each of the SST-Rs. SST-R2 and SST-R5x3 were expressed on LH and FSH cells, while SST-R5 was exclusively expressed on LH cells. Interestingly, SST-R3, which was expressed on GH secreting cells, was also expressed on both gonadotropin-secreting cells. Transactivation assays, using COS7 cell line transfected with tilapia SST-Rs together with the reporter plasmid CRE-luc, demonstrated an effect through the cAMP/PKA pathway. Signal transduction analysis demonstrated that SST agonist (Octreotide; IC50 = 0.8-60nM) decreased the cAMP/PKA pathway, while an opposite effect was found when SST antagonist (Cyclosomatostatin; EC50 = 0.1 - 188 nM) was used. To understand the physiological effects of somatostatin on gonadotropins and GH release, we examined the effect of ip injection (100 μg/kg BW) of somatostatin agonist and antagonist on plasma FSH, LH and GH levels. SST agonist decreased plasma GH and FSH levels, as fast as two hours post injection and their levels remained low until the end of the experiment. On the other hand, SST antagonist increased LH and FSH levels two hours post injection, but while FSH levels remained high during the entire experiment, LH levels went back to basal levels afterwards. Our results show - for the first time in fish - a direct effect of SST on gonadotropin release, that could serve as a bridge between the GH-axis and the GTH-axis. The research was funded by the Israel Science Foundation (ISF) no. 1540/17.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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  • 5
    Online Resource
    Online Resource
    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A529-A530
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A529-A530
    Abstract: The pivotal role of the gonadotropins (GtHs) luteinizing hormone (LH) and follicle stimulating hormone (FSH) in vertebrate reproduction is well documented. LH and FSH bind to the leucine-rich repeats of the extracellular domains of their cognate receptors (R) in the gonads to actuate steroidogenesis and gametogenesis. Though these GtHs specifically bind only to their cognate receptors in mammals, this interaction becomes inconsistent in the case of fish. Whilst in some fish species the gonadotropins show receptor specificity much like their mammalian homologs, FSH and LH have demonstrated mutual and/or singular cross-activation of the FSH and/or LH receptors in several fish species. These complications regarding receptor specificity are further magnified by cross activation by orthologous GtHs from different species. So far no consistent pattern has been established to chart or predict this cross-talk in specific species or higher taxonomic orders. In the current study, we strived to understand the promiscuous nature of FSH and LH through in silico perspectives. While our studies in Russian sturgeon (Acipenser gueldenstaedtii) have shown FSH and LH to exhibit mutual promiscuity but of varying magnitude, in common carp (Cyprinus carpio) only LH showed singular cross-activation of FSHR. In Nile tilapia (Oreochromis niloticus) these gonadotropins exhibited strict specificity towards their cognate receptors similar to humans. Taking these species as representatives of varying degrees of cognate binding shown by the gonadotropins, we have generated docked models of these hormones and the extracellular domain of these receptors using in silico tools. We have further tried to compare these models, their docked poses, and key residues involved in the binding of these hormone-receptor complexes. We have further tried to compare parameters such as phosphorylation sites, N-linked glycosylation motifs, surface charge, etc. of these models to better understand the docking of these complexes. Our results suggest that in cases of cross activation by FSH and/or LH within or across the species, though binding sites are present at the leucine rich repeats on concaved face of the receptor extracellular domain, the docked position and residues involved in binding may vary significantly. Furthermore, though the seatbelt loop and GTHβ loop-2 (gonadotropin hormone subunit- beta) of the gonadotropin hormones act as the key players in binding, the docking of the hormone may vary in conformation. Due the large size and flexibility of these hormones and the receptor binding interface, it seems apparent that there are multiple binding sites that activate the resulting signaling pathway. Our study aspires to provide better insights towards the promiscuous nature of these hormones and attempt to overcome the handicap of lack of individual physical models using in silico tools.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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  • 6
    Online Resource
    Online Resource
    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A557-A557
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A557-A557
    Abstract: From mammals to fish, gametogenesis and sexual maturation are driven by LH and FSH, the two gonadotropic hormones temporally secreted from the pituitary. Teleost fish are an excellent model for addressing the unique regulation and function of each gonadotropin hormone since, unlike mammals; they synthesize and secrete LH and FSH from distinct cells. By performing cell specific transcriptome analysis of double-labelled transgenic Nile tilapia (Oreochromis niloticus) expressing GFP and RFP in LH or FSH cells, respectively, we identified genes specifically enriched in each cell type. Though GnRH is considered the main neuropeptide regulating LH and FSH, we found that each LH and FSH cell express unique GPCR signature that reveals the direct regulation of additional metabolic and homeostatic hormones (like cholecystokinin, somatostatin and glutamate). Moreover, some of those GPCRs were conserved also in gonadotrophs of mammals (like PACAP receptor, Adropin receptor and GABBA receptor). Next, we had exploited the unique behavior of Nile tilapia where a behavioral hierarchy is created between males, to compare the gene expression in the pituitary and brain of dominant (reproducing) males to a subordinate (non-reproducing) males. By combining the two transcriptome sets we had identified novel players in the hypothalamic regulation of the HPG axis, and revealed how brain aromatase (cyp19a1b), that is enriched specifically in LH cells, is the key factor in regulating the activity of LH and FSH cells in dominant reproducing fish. Thereby, unraveling novel mechanisms in the differential regulation of LH and FSH. The research was funded by the Israel Science Foundation (ISF) no. 1540/17.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
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  • 7
    In: Endocrinology, The Endocrine Society, Vol. 156, No. 8 ( 2015-08), p. 3026-3037
    Type of Medium: Online Resource
    ISSN: 0013-7227 , 1945-7170
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2015
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  • 8
    Online Resource
    Online Resource
    The Endocrine Society ; 2022
    In:  Endocrinology Vol. 163, No. 2 ( 2022-02-01)
    In: Endocrinology, The Endocrine Society, Vol. 163, No. 2 ( 2022-02-01)
    Abstract: Vasoactive intestinal peptide (Vip) regulates luteinizing hormone (LH) release through the direct regulation of gonadotropin-releasing hormone (GnRH) neurons at the level of the brain in female rodents. However, little is known regarding the roles of Vip in teleost reproduction. Although GnRH is critical for fertility through the regulation of LH secretion in vertebrates, the exact role of the hypophysiotropic GnRH (GnRH3) in zebrafish is unclear since GnRH3 null fish are reproductively fertile. This phenomenon raises the possibility of a redundant regulatory pathway(s) for LH secretion in zebrafish. Here, we demonstrate that VipA (homologues of mammalian Vip) both inhibits and induces LH secretion in zebrafish. Despite the observation that VipA axons may reach the pituitary proximal pars distalis including LH cells, pituitary incubation with VipA in vitro, and intraperitoneal injection of VipA, did not induce LH secretion and lhβ mRNA expression in sexually mature females, respectively. On the other hand, intracerebroventricular administration of VipA augmented plasma LH levels in both wild-type and gnrh3-/- females at 1 hour posttreatment, with no observed changes in pituitary GnRH2 and GnRH3 contents and gnrh3 mRNA levels in the brains. While VipA’s manner of inhibition of LH secretion has yet to be explored, the stimulation seems to occur via a different pathway than GnRH3, dopamine, and 17β-estradiol in regulating LH secretion. The results indicate that VipA induces LH release possibly by acting with or through a non-GnRH factor(s), providing proof for the existence of functional redundancy of LH release in sexually mature female zebrafish.
    Type of Medium: Online Resource
    ISSN: 0013-7227 , 1945-7170
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
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  • 9
    Online Resource
    Online Resource
    The Endocrine Society ; 2015
    In:  Endocrinology Vol. 156, No. 11 ( 2015-11-01), p. 4163-4173
    In: Endocrinology, The Endocrine Society, Vol. 156, No. 11 ( 2015-11-01), p. 4163-4173
    Abstract: The function and components of the hypothalamic-pituitary axis are conserved among vertebrates; however, in fish, a neuroglandular mode of delivery (direct contact between axons and endocrine cells) was considered dominant, whereas in tetrapods hypothalamic signals are relayed to their targets via the hypophysial portal blood system (neurovascular delivery mode). By using a transgenic zebrafish model we studied the functional and anatomical aspects of gonadotrope regulation thus revisiting the existing model. FSH cells were found to be situated close to the vasculature whereas the compact organization of LH cells prevented direct contact of all cells with the circulation. GnRH3 fibers formed multiple boutons upon reaching the pituitary, but most of these structures were located in the neurohypophysis rather than adjacent to gonadotropes. A close association was observed between FSH cells and GnRH3 boutons, but only a fifth of the LH cells were in direct contact with GnRH3 axons, suggesting that FSH cells are more directly regulated than LH cells. GnRH3 fibers closely followed the vasculature in the neurohypophysis and formed numerous boutons along these tracts. These vessels were found to be permeable to relatively large molecules, suggesting the uptake of GnRH3 peptides. Our findings have important implications regarding the differential regulation of LH and FSH and contradict the accepted notion that fish pituitary cells are mostly regulated directly by hypothalamic fibers. Instead, we provide evidence that zebrafish apply a dual mode of gonadotrope regulation by GnRH3 that combines both neuroglandular and neurovascular components.
    Type of Medium: Online Resource
    ISSN: 0013-7227 , 1945-7170
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2015
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  • 10
    Online Resource
    Online Resource
    The Endocrine Society ; 2008
    In:  Endocrinology Vol. 149, No. 4 ( 2008-04-01), p. 1687-1696
    In: Endocrinology, The Endocrine Society, Vol. 149, No. 4 ( 2008-04-01), p. 1687-1696
    Type of Medium: Online Resource
    ISSN: 0013-7227 , 1945-7170
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2008
    detail.hit.zdb_id: 2011695-0
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