scholarly journals Evidence for a Novel Intrapituitary Autocrine/Paracrine Feedback Loop Regulating Growth Hormone Synthesis and Secretion in Grass Carp Pituitary Cells by Functional Interactions between Gonadotrophs and Somatotrophs

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5548-5559 ◽  
Author(s):  
Hong Zhou ◽  
Xinyan Wang ◽  
Wendy K. W. Ko ◽  
Anderson O. L. Wong
Keyword(s):  
Mrna Expression ◽  
Grass Carp ◽  
Feedback Loop ◽  
Cell Model ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Local Interactions ◽  
Hormone Synthesis ◽  
A Cell ◽  
High Doses

Abstract Gonadotropin (GTH) and GH released from the pituitary are known to interact at multiple levels to modulate the functions of the gonadotrophic and somatotrophic axes. However, their interactions at the pituitary level have not been fully characterized. In this study, autocrine/paracrine regulation of GH synthesis and secretion by local interactions between gonadotrophs and somatotrophs was examined using grass carp pituitary cells as a cell model. Exogenous GTH and GH induced GH release and GH mRNA expression in carp pituitary cells. Removal of endogenous GTH and GH by immunoneutralization with GTH and GH antisera, respectively, suppressed GH release, GH production, and GH mRNA levels. GH antiserum also blocked the stimulatory effects of exogenous GTH on GH release and GH mRNA levels. In reciprocal experiments, GH release and GH mRNA expression induced by exogenous GH was significantly reduced by GTH antiserum. In addition, exogenous GH was found to be inhibitory to basal GTH release and treatment with GH antiserum elevated GTH secretion at low doses but suppressed GTH production at high doses. These results suggest that local interactions between gonadotrophs and somatotrophs may form an intrapituitary feedback loop to regulate GH release and synthesis. In this model, GTH released from gonadotrophs induces GH release and GH production in neighboring somatotrophs. GH secreted maintains somatotroph sensitivity to GTH stimulation, and at the same time, inhibits basal GTH release in gonadotrophs. This feedback loop may represent a novel mechanism regulating GH release and synthesis in lower vertebrates.

scholarly journals Modulation of Calmodulin Gene Expression as a Novel Mechanism for Growth Hormone Feedback Control by Insulin-like Growth Factor in Grass Carp Pituitary Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 3821-3835 ◽  
Author(s):  
Longfei Huo ◽  
Guodong Fu ◽  
Xinyan Wang ◽  
Wendy K. W. Ko ◽  
Anderson O. L. Wong
Keyword(s):  
Gene Expression ◽  
Feedback Control ◽  
Grass Carp ◽  
Cell Model ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Hormone Synthesis ◽  
Igf I ◽  
Gh Gene

Abstract Calmodulin (CaM), the Ca2+ sensor in living cells, is essential for biological functions mediated by Ca2+-dependent mechanisms. However, modulation of CaM gene expression at the pituitary level as a means to regulate pituitary hormone synthesis has not been characterized. In this study we examined the functional role of CaM in the feedback control of GH by IGF using grass carp pituitary cells as a cell model. To establish the structural identity of CaM expressed in the grass carp, a CaM cDNA, CaM-L, was isolated from the carp pituitary using 3′/5′ rapid amplification of cDNA ends. The open reading frame of this cDNA encodes a 149-amino acid protein sharing the same primary structure with CaMs reported in mammals, birds, and amphibians. This CaM cDNA is phylogenetically related to the CaM I gene family, and its transcripts are ubiquitously expressed in the grass carp. In carp pituitary cells, IGF-I and IGF-II induced CaM mRNA expression with a concurrent drop in GH transcript levels. These stimulatory effects on CaM mRNA levels were not mimicked by insulin and appeared to be a direct consequence of IGF activation of CaM gene transcription without altering CaM transcript stability. CaM antagonism and inactivation of calcineurin blocked the inhibitory effects of IGF-I and IGF-II on GH gene expression, and CaM overexpression also suppressed the 5′ promoter activity of the grass carp GH gene. These results, as a whole, provide evidence for the first time that IGF feedback on GH gene expression is mediated by activation of CaM gene expression at the pituitary level.

Grass carp somatolactin: II. Pharmacological study on postreceptor signaling mechanisms for PACAP-induced somatolactin-α and -β gene expression

2008 ◽  
Vol 295 (2) ◽  
pp. E477-E490 ◽  
Author(s):  
Quan Jiang ◽  
Mulan He ◽  
Xinyan Wang ◽  
Anderson O. L. Wong
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Grass Carp ◽  
Pharmacological Study ◽  
Primary Cultures ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Fish Model ◽  
Subsequent Activation

Somatolactin (SL), the latest member of the growth hormone/prolactin family, is a novel pituitary hormone with diverse functions. However, the signal transduction mechanisms responsible for SL expression are still largely unknown. Using grass carp as an animal model, we examined the direct effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on SL gene expression at the pituitary level. In primary cultures of grass carp pituitary cells, SLα and SLβ mRNA levels could be elevated by PACAP via activation of PAC-I receptors. With the use of a pharmacological approach, the AC/cAMP/PKA and PLC/inositol 1,4,5-trisphosphate (IP3)/PKC pathways and subsequent activation of the Ca2+/calmodulin (CaM)/CaMK-II cascades were shown to be involved in PACAP-induced SLα mRNA expression. Apparently, the downstream Ca2+/CaM-dependent cascades were triggered by extracellular Ca2+ ([Ca2+]e) entry via L-type voltage-sensitive Ca2+ channels (VSCC) and Ca2+ release from IP3-sensitive intracellular Ca2+ stores. In addition, the VSCC component could be activated by cAMP/PKA- and PLC/PKC-dependent mechanisms. Similar postreceptor signaling cascades were also observed for PACAP-induced SLβ mRNA expression, except that [Ca2+]e entry through VSCC, PKC coupling to PLC, and subsequent activation of CaMK-II were not involved. These findings, taken together, provide evidence for the first time that PACAP can induce SLα and SLβ gene expression in fish model via PAC-I receptors through differential coupling to overlapping and yet distinct signaling pathways.

scholarly journals Paracrine regulation of growth hormone gene expression by gonadotrophin release in grass carp pituitary cells: functional implications, molecular mechanisms and signal transduction

2005 ◽  
Vol 34 (2) ◽  
pp. 415-432 ◽  
Author(s):  
Hong Zhou ◽  
Yonghua Jiang ◽  
Wendy K W Ko ◽  
Wensheng Li ◽  
Anderson O L Wong
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Adenylate Cyclase ◽  
Mrna Expression ◽  
Grass Carp ◽  
Janus Kinase ◽  
Growth Hormone Gene ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Gh Gene

Growth hormone (GH) is known to stimulate luteinizing hormone (LH) release via paracrine interactions between somatotrophs and gonadotrophs. However, it is unclear if LH can exert a reciprocal effect to modulate somatotroph functions. Here we examined the paracrine effects of LH on GH gene expression using grass carp pituitary cells as a cell model. LH receptors were identified in grass carp somatotrophs and their activation by human chorionic gonadotropin (hCG) increased ‘steady-state’ GH mRNA levels. Removal of endogenous LH by immunoneutralization using LH antiserum inhibited GH release and GH mRNA expression. GH secretagogues, including gonadotrophin releasing hormone (GnRH), pituitary adenylate cyclase-activating polypeptide (PACAP) and apomorphine, were effective in elevating GH mRNA levels but these stimulatory actions were blocked by LH antiserum. In pituitary cells pretreated with actinomycin D, the half-life of GH mRNA was not affected by hCG but was enhanced by LH immunoneutralization. Treatment with LH antiserum also suppressed basal levels of mature GH mRNA and primary transcripts. hCG increased cAMP synthesis in carp pituitary cells and hCG-induced GH mRNA expression was mimicked by forskolin but suppressed by inhibiting adenylate cyclase and protein kinase A. Similarly, the stimulatory actions of hCG and forskolin on GH mRNA expression were blocked by inhibiting Janus kinase 2 (JAK2) and MAP kinase (MAPK), including P42/44MAPK and P38 MAPK. These results suggest that LH is essential for the maintenance of GH release, GH gene expression, and somatotroph responsiveness to GH-releasing factors. The paracrine actions of LH on GH mRNA expression are mediated by a concurrent increase in GH gene transcription and GH mRNA turnover, probably through JAK2/MAPK coupled to the cAMP-dependent pathway.

Somatostatin-28 inhibitory action on somatolactin-α and -β gene expression in goldfish

2014 ◽  
Vol 307 (6) ◽  
pp. R755-R768 ◽  
Author(s):  
Quan Jiang ◽  
Anderson O. L. Wong
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Primary Cultures ◽  
Inhibitory Effect ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Structural Identity ◽  
Rapid Amplification ◽  
Differential Coupling

Somatostain (SS) is known to inhibit growth hormone (GH) and prolactin (PRL) secretion. Somatolactin (SL) is a member of the GH/PRL family, but its regulation by goldfish brain somatostatin-28 (gbSS-28) has not been examined. To this end, the structural identity of goldfish SLα was established by 5′/3′-rapid amplification of cDNA ends. As revealed by in situ hybridization and immunohistochemical staining, the expression of SL isoforms was detected in pituitary cells located in the neurointermediate lobe (NIL). The transcripts of goldfish SS receptor 5a (Sst5a) but not Sst1b, Sst2, or Sst3a were detected in the goldfish NIL cells by RT-PCR. In goldfish pituitary cells, gbSS-28 not only had an inhibitory effect on basal SLα and SLβ mRNA levels but also could abolish insulin-like growth factor-stimulated SL gene expression. In primary cultures of goldfish NIL cells, gbSS-28 reduced forskolin-stimulated total cAMP production. With the use of a pharmacological approach, the adenylate cyclase (AC)/cAMP and phospholipase C (PLC)/inositol trisphosphate (IP3)/protein kinase C (PKC) cascades were shown to be involved in gbSS-28-inhibited SLα mRNA expression. Similar postreceptor signaling cascades were also observed for gbSS-28-reduced SLβ mRNA expression, except that PKC coupling to PLC was not involved. These results provide evidence that gbSS-28 can inhibit SLα and SLβ gene expression at the goldfish pituitary level via Sst5 through differential coupling of AC/cAMP and PLC/IP3/PKC cascades.

scholarly journals TAC1 Gene Products Regulate Pituitary Hormone Secretion and Gene Expression in Prepubertal Grass Carp Pituitary Cells

Endocrinology ◽  
2017 ◽  
Vol 158 (6) ◽  
pp. 1776-1797 ◽  
Author(s):  
Guangfu Hu ◽  
Mulan He ◽  
Wendy K. W. Ko ◽  
Anderson O. L. Wong
Keyword(s):  
Protein Kinase ◽  
Mrna Expression ◽  
Grass Carp ◽  
Messenger Rna ◽  
Hormone Secretion ◽  
Adenosine Monophosphate ◽  
Pituitary Hormone ◽  
Neurokinin A ◽  
Pituitary Cells ◽  
Gene Products

Abstract Tachykinin-1 (TAC1) is known to have diverse functions in mammals, but similar information is scarce in fish species. Using grass carp as a model, the pituitary actions, receptor specificity and postreceptor signaling of TAC1 gene products, namely substance P (SP) and neurokinin A (NKA), were examined. TAC1 encoding SP and NKA as well as tachykinin receptors NK1R and NK2R were cloned in the carp pituitary. The newly cloned receptors were shown to be functional with properties similar to mammalian counterparts. In carp pituitary cells, SP and NKA could trigger luteinizing hormone (LH), prolactin (PRL), and somatolactin α (SLα) secretion, with parallel rises in PRL and SLα transcripts. Short-term SP treatment (3 hours) induced LH release, whereas prolonged induction (24 hours) could attenuate LHβ messenger RNA (mRNA) expression. At pituitary cell level, LH, PRL, and SLα regulation by TAC1 gene products were mediated by NK1R, NK2R, and NK3R, respectively. Apparently, SP- and NKA-induced LH and SLα secretion and transcript expression were mediated by adenylyl cyclase/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), phospholiphase C (PLC)/inositol 1,4,5-triphosphate/protein kinase C (PKC), and Ca2+/calmodulin (CaM)/CaM-dependent protein kinase-II pathways. The signal transduction for PRL responses was similar, except for the absence of a PKC component. Regarding SP inhibition of LHβ mRNA expression, the cAMP/PKA- and PLC/PKC-dependent (but not Ca2+/CaM-dependent) cascades were involved. These results, as a whole, suggest that TAC1 gene products play a role in LH, PRL, and SLα regulation via overlapping postreceptor signaling coupled to different subtypes of tachykinin receptor expressed in the carp pituitary.

scholarly journals Goldfish Calmodulin: Molecular Cloning, Tissue Distribution, and Regulation of Transcript Expression in Goldfish Pituitary Cells

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5056-5067 ◽  
Author(s):  
Longfei Huo ◽  
Eric K. Y. Lee ◽  
P. C. Leung ◽  
Anderson O. L. Wong
Keyword(s):  
Amino Acid ◽  
Adenylate Cyclase ◽  
Mrna Expression ◽  
Hormone Secretion ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Reading Frame ◽  
Pituitary Adenylate Cyclase ◽  
Neuroendocrine Mechanisms

Abstract Calmodulin (CaM) is a Ca2+-binding protein essential for biological functions mediated through Ca2+-dependent mechanisms. In the goldfish, CaM is involved in the signaling events mediating pituitary hormone secretion induced by hypothalamic factors. However, the structural identity of goldfish CaM has not been established, and the neuroendocrine mechanisms regulating CaM gene expression at the pituitary level are still unknown. Here we cloned the goldfish CaM and tested the hypothesis that pituitary expression of CaM transcripts can be the target of modulation by hypothalamic factors. Three goldfish CaM cDNAs, namely CaM-a, CaM-bS, and CaM-bL, were isolated by library screening. These cDNAs carry a 450-bp open reading frame encoding the same 149-amino acid CaM protein, the amino acid sequence of which is identical with that of mammals, birds, and amphibians and is highly homologous (≥90%) to that in invertebrates. In goldfish pituitary cells, activation of cAMP- or PKC-dependent pathways increased CaM mRNA levels, whereas the opposite was true for induction of Ca2+ entry. Basal levels of CaM mRNA was accentuated by GnRH and pituitary adenylate cyclase-activating polypeptide but suppressed by dopaminergic stimulation. Pharmacological studies using D1 and D2 analogs revealed that dopaminergic inhibition of CaM mRNA expression was mediated through pituitary D2 receptors. At the pituitary level, D2 activation was also effective in blocking GnRH- and pituitary adenylate cyclase-activating polypeptide-stimulated CaM mRNA expression. As a whole, the present study has confirmed that the molecular structure of CaM is highly conserved, and its mRNA expression at the pituitary level can be regulated by interactions among hypothalamic factors.

scholarly journals Reproductive Regulation of PrRPs in Teleost: The Link Between Feeding and Reproduction

2021 ◽  
Vol 12 ◽  
Author(s):  
Chuanhui Xia ◽  
Xiangfeng Qin ◽  
Lingling Zhou ◽  
Xuetao Shi ◽  
Tianyi Cai ◽  
...  
Keyword(s):  
Food Intake ◽  
Mrna Expression ◽  
Grass Carp ◽  
Coupling Factor ◽  
Pituitary Cells ◽  
Reproductive Regulation ◽  
Serum Luteinizing Hormone ◽  
Anorexigenic Peptide ◽  
Reproductive Activities ◽  
Lh Secretion

Prolactin-releasing peptide (PrRP), a sort of vital hypothalamic neuropeptide, has been found to exert an enormous function on the food intake of mammals. However, little is known about the functional role of PrRP in teleost. In the present study, two PrRP isoforms and four PrRP receptors were isolated from grass carp. Ligand-receptor selectivity displayed that PrRP1 preferentially binds with PrRP-R1a and PrRP-R1b, while PrRP-R2a and PrRP-R2b were special receptors for PrRP2. Tissue distribution indicated that both PrRPs and PrRP-Rs were highly expressed in the hypothalamus-pituitary-gonad axis and intestine, suggesting a latent function on food intake and reproduction. Using grass carp as a model, we found that food intake could significantly induce hypothalamus PrRP mRNA expression, which suggested that PrRP should be also an anorexigenic peptide in teleost. Interestingly, intraperitoneal (IP) injection of PrRPs could significantly induce serum luteinizing hormone (LH) secretion and pituitary LHβ and GtHα mRNA expression in grass carp. Moreover, using primary culture grass carp pituitary cells as a model, we further found that PrRPs could directly induce pituitary LH secretion and synthesis mediated by AC/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-II pathways. Finally, estrogen treatment of prepubertal fish elicited increases in PrRPs and PrPR receptors expression in primary cultured grass carp hypothalamus cells, which further confirmed that the PrRP/PrRPR system may participate in the neuroendocrine control of fish reproduction. These results, taken together, suggest that PrRPs might act as a coupling factor in feeding metabolism and reproductive activities in teleost.

scholarly journals The defect in Fas mRNA expression in MRL/lpr mice is associated with insertion of the retrotransposon, ETn.

1993 ◽  
Vol 178 (2) ◽  
pp. 723-730 ◽  
Author(s):  
J L Chu ◽  
J Drappa ◽  
A Parnassa ◽  
K B Elkon
Keyword(s):  
Mrna Expression ◽  
Tumor Necrosis Factor Receptor ◽  
Growth Factor Receptor ◽  
Surface Protein ◽  
Northern Blotting ◽  
Nucleotide Sequencing ◽  
Mrna Levels ◽  
Wild Type ◽  
Fas Mrna ◽  
A Cell

Fas is a cell surface protein of the tumor necrosis factor receptor, nerve growth factor receptor, CD40 family, and is involved in the control of lymphocyte apoptosis. A mutation in the Fas gene in MRL/lpr mice results in massive lymphoproliferation (lpr) and accelerated autoimmunity. To further study the nature of this defect, Fas mRNA expression was evaluated by reverse transcriptase polymerase chain reaction as well as by Northern blotting. These studies revealed that the wild-type Fas message was produced at approximately 10-fold lower levels in the lpr compared with the ++ substrain of MRL mice. In addition to the wild-type transcript, lpr mice also synthesized chimeric transcripts containing an insertion of the early retrotransposon (ETn). Molecular cloning and nucleotide sequencing of a Fas-ETn chimeric cDNA suggested that the striking reduction in wild-type Fas mRNA levels and the presence of aberrant transcripts in MRL/lpr mice are most likely explained by the insertion of the ETn retrotransposon into an intron of the Fas gene and induction of alternative splicing involving the 5' ETn long terminal repeat.

scholarly journals Novel Pituitary Actions of Epidermal Growth Factor: Receptor Specificity and Signal Transduction for UTS1, EGR1, and MMP13 Regulation by EGF

2019 ◽  
Vol 20 (20) ◽  
pp. 5172 ◽  
Author(s):  
Qiongyao Hu ◽  
Shaohua Xu ◽  
Cheng Ye ◽  
Jingyi Jia ◽  
Lingling Zhou ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mrna Expression ◽  
Grass Carp ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Receptor Specificity ◽  
Epidermal Growth

Epidermal growth factor (EGF) is a member of the EGF-like ligands family, which plays a vital role in cell proliferation, differentiation, and folliculogenesis through binding with EGF receptors, including ErbB1 (EGFR/HER1), ErbB2 (HER2), ErbB3 (HER3), and ErbB4 (HER4). In mammals, many functional roles of EGF have been reported in the ovaries and breasts. However, little is known about the functions of EGF in the pituitary, especially in teleost. In this study, using grass carp pituitary cells as the model, we try to examine the direct pituitary actions of EGF in teleost. Firstly, transcriptomic analysis showed that 599 different expressed genes (DEGs) between the control and EGF-treatment group were mainly involved in cell proliferation, cell migration, signal transduction, and transcriptional regulation. Then, we further confirmed that EGF could significantly induce UTS1, EGR1, and MMP13 mRNA expression in a time-and dose-dependent manner. The stimulatory actions of EGF on UTS1 and EGR1 mRNA expression were mediated by the MEK1/2/ERK1/2 and PI3K/AKT/mTOR pathways coupled with both ErbB1 and ErbB2 in grass carp pituitary cells. The receptor specificity and signal transductions for the corresponding responses on MMP13 mRNA expression were also similar, except that the ErbB2 and PI3K/AKT/mTOR pathway were not involved. As we know, MMP13 could release EGF from HB-EGF. Interestingly, our data also showed that the MMPs inhibitor BB94 could suppress EGF-induced UTS1 and EGR1 mRNA expression. These results, taken together, suggest that the stimulatory actions of EGF on UTS1 and EGR1 mRNA expression could be enhanced by EGF-induced MMP13 expression in the pituitary.

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