scholarly journals Interferon-γ inhibits cellular proliferation and ACTH production in corticotroph tumor cells through a novel janus kinases–signal transducer and activator of transcription 1/nuclear factor-kappa B inhibitory signaling pathway

2008 ◽  
Vol 199 (2) ◽  
pp. 177-189 ◽  
Author(s):  
Marta Labeur ◽  
Damian Refojo ◽  
Barbara Wölfel ◽  
Johanna Stalla ◽  
Vivian Vargas ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Transcriptional Repression ◽  
Inhibitory Action ◽  
Cellular Proliferation ◽  
Hormone Secretion ◽  
Interferon Γ ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Signal Transducer ◽  
Janus Kinases

Interferon-γ (IFNG) is a cytokine that exerts potent antiproliferative and tumoricidal effects in a variety of cancers. Moreover, IFNG modulates normal pituitary hormone secretion, and was shown to inhibit the expression of the ACTH precursor POMC in murine ACTH-secreting AtT-2010/21/2008 tumor cells. We have studied the functional role of IFNG on pituitary tumor cells, focusing on the involvement of IFNG in the molecular events leading to the control of POMC transcriptional repression. Herein, it is shown that IFNG inhibits AtT-20 tumor cell proliferation without inducing apoptosis. Unexpectedly, an activated janus kinases–signal transducer and activator of transcription (JAK–STAT1) cascade is required for IFNG inhibitory action on POMC promoter activity. Factor-kappa B (NF-κB) is necessary for the inhibitory action of IFNG on Pomc transcription, since loss of NF-κB activity with IκB super-repressor abolishes this effect. In addition, 1 and 2 IFNG receptor immunoreactivity was detected in human corticotropinoma cells. Interestingly, IFNG inhibits ACTH production from these cells in primary cell culture, without affecting basal ACTH biosynthesis in normal non-tumoral pituitary cells. In conclusion, our data show for the first time that POMC transcription can be negatively regulated by a JAK–STAT1 and NF-κB-dependent pathway.

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 Signal Transduction Mechanisms for Glucagon-Induced Somatolactin Secretion and Gene Expression in Nile Tilapia (Oreochromis niloticus) Pituitary Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Chaoyi Zhang ◽  
Anji Lian ◽  
Yue Xu ◽  
Quan Jiang
Keyword(s):  
Gene Expression ◽  
Oreochromis Niloticus ◽  
Nile Tilapia ◽  
Primary Cultures ◽  
Hormone Secretion ◽  
Hek293 Cells ◽  
Luciferase Reporter ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Mrna Levels

Glucagon (GCG) plays a stimulatory role in pituitary hormone regulation, although previous studies have not defined the molecular mechanism whereby GCG affects pituitary hormone secretion. To this end, we identified two distinct proglucagons, Gcga and Gcgb, as well as GCG receptors, Gcgra and Gcgrb, in Nile tilapia (Oreochromis niloticus). Using the cAMP response element (CRE)-luciferase reporter system, tilapia GCGa and GCGb could reciprocally activate the two GCG receptors expressed in human embryonic kidney 293 (HEK293) cells. Quantitative real-time PCR analysis revealed that differential expression of the Gcga and Gcgb and their cognate receptors Gcgra and Gcgrb was found in the various tissues of tilapia. In particular, the Gcgrb is abundantly expressed in the neurointermediate lobe (NIL) of the pituitary gland. In primary cultures of tilapia NIL cells, GCGb effectively stimulated SL release, with parallel rises in the mRNA levels, and co-incubation with the GCG antagonist prevented GCGb-stimulated SL release. In parallel experiments, GCGb treatment dose-dependently enhanced intracellular cyclic adenosine monophosphate (cAMP) accumulation with increasing inositol 1,4,5-trisphosphate (IP3) concentration and the resulting in transient increases of Ca2+ signals in the primary NIL cell culture. Using selective pharmacological approaches, the adenylyl cyclase (AC)/cAMP/protein kinase A (PKA) and phospholipase C (PLC)/IP3/Ca2+/calmodulin (CaM)/CaMK-II pathways were shown to be involved in GCGb-induced SL release and mRNA expression. Together, these results provide evidence for the first time that GCGb can act at the pituitary level to stimulate SL release and gene expression via GCGRb through the activation of the AC/cAMP/PKA and PLC/IP3/Ca2+/CaM/CaMK-II cascades.

Characterization of endothelin receptors in the anterior pituitary gland

1993 ◽  
Vol 265 (4) ◽  
pp. E601-E608 ◽  
Author(s):  
B. Kanyicska ◽  
M. E. Freeman
Keyword(s):  
Primary Cultures ◽  
Hormone Secretion ◽  
Pituitary Hormone ◽  
Receptor Subtypes ◽  
Pituitary Cells ◽  
Female Rat ◽  
Response Curves ◽  
Potency Ratio ◽  
Eta Receptor ◽  
Rat Pituitary Cells

To characterize endothelin (ET) receptors modulating pituitary hormone secretion, potencies of ET-like agonists were compared on prolactin (PRL), thyrotropin (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) secretion from primary cultures of female rat pituitary cells. ET-1 was more potent than ET-3 in all cases. Sarafotoxin (SRTX) S6b an ETA agonist, was also more potent than ET-3 in all cases. SRTX-c, an ETB receptor agonist, was inactive. The ET-1-to-ET-3 potency ratio was three orders of magnitude higher on PRL or TSH secretion than on LH and FSH secretion, whereas SRTX-b-to-ET-3 potency ratios were similar on all four hormones. The ETA antagonist BQ-123 caused a parallel dextral displacement of dose-response curves of ET-1 and ET-3 on all four hormones. Schild regressions for BQ-123 on ET-1-induced PRL, TSH, LH, and FSH secretion indicated that BQ-123 has a similar affinity for the receptors mediating ET-1's effects. When BQ-123 was assessed against ET-3, Schild regressions indicated greater affinity for ET-3 on lactotrophs and thyrotrophs than gonadotrophs. Thus changes in pituitary hormone secretion are mediated by ETA-like receptors. ET receptors in lactotrophs and thyrotrophs are clearly distinguishable from gonadotrophs. We suggest the existence of distinct ETA receptor subtypes (ETA1 and ETA2) on these differing pituitary cells.

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 Clusterin is expressed in the anterior and intermediate lobes, but not in the posterior pituitary of sheep

1999 ◽  
Vol 23 (2) ◽  
pp. 199-208 ◽  
Author(s):  
JS Fleming ◽  
NM Hope ◽  
CJ Bolter
Keyword(s):  
Anterior Part ◽  
Hormone Secretion ◽  
In Situ Hybridisation ◽  
Cdna Probe ◽  
Northern Blotting ◽  
Secretory Cells ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Posterior Pituitary ◽  
Lipid Uptake

We have examined the expression of the ovine clusterin gene in the sheep pituitary gland, with the aim of determining its site of synthesis in this tissue. Northern blotting analysis of extracted polyadenylated RNA, using a (32)P-labelled rat clusterin cDNA probe, detected the greatest amounts of clusterin mRNA in the anterior part of dissected pituitary glands. In situ hybridisation studies showed clusterin mRNA in anterior and intermediate pituitary cells, with lower amounts in vascular endothelium and posterior pituicytes. Clusterin protein, detected by immunohistochemistry, was observed in some single secretory cells, within the capillary lumen and in cells around capillaries in the anterior and intermediate lobes, but no immunoreactivity was observed in posterior pituitary tissue. The pattern of clusterin expression in anterior and intermediate pituitary cells suggests possible roles for the protein in secretory cell turnover and/or hormone secretion or lipid uptake. Clusterin does not appear to be involved in ovine posterior pituitary hormone neurosecretion.

scholarly journals Inhibin at 90: From Discovery to Clinical Application, a Historical Review

2014 ◽  
Vol 35 (5) ◽  
pp. 747-794 ◽  
Author(s):  
Yogeshwar Makanji ◽  
Jie Zhu ◽  
Rama Mishra ◽  
Chris Holmquist ◽  
Winifred P. S. Wong ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Physiological Role ◽  
Historical Review ◽  
Reproductive Function ◽  
Reproductive Hormones ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Organ Systems ◽  
Hypophysiotropic Hormone

When it was initially discovered in 1923, inhibin was characterized as a hypophysiotropic hormone that acts on pituitary cells to regulate pituitary hormone secretion. Ninety years later, what we know about inhibin stretches far beyond its well-established capacity to inhibit activin signaling and suppress pituitary FSH production. Inhibin is one of the major reproductive hormones involved in the regulation of folliculogenesis and steroidogenesis. Although the physiological role of inhibin as an activin antagonist in other organ systems is not as well defined as it is in the pituitary-gonadal axis, inhibin also modulates biological processes in other organs through paracrine, autocrine, and/or endocrine mechanisms. Inhibin and components of its signaling pathway are expressed in many organs. Diagnostically, inhibin is used for prenatal screening of Down syndrome as part of the quadruple test and as a biochemical marker in the assessment of ovarian reserve. In this review, we provide a comprehensive summary of our current understanding of the biological role of inhibin, its relationship with activin, its signaling mechanisms, and its potential value as a diagnostic marker for reproductive function and pregnancy-associated conditions.

scholarly journals Is bursting more effective than spiking in evoking pituitary hormone secretion? A spatiotemporal simulation study of calcium and granule dynamics

2016 ◽  
Vol 310 (7) ◽  
pp. E515-E525 ◽  
Author(s):  
Alessia Tagliavini ◽  
Joël Tabak ◽  
Richard Bertram ◽  
Morten Gram Pedersen
Keyword(s):  
Electrical Activity ◽  
Endocrine Cells ◽  
Hormone Secretion ◽  
Cell Activity ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Hormone Release ◽  
Channel Activity ◽  
Spatiotemporal Simulation ◽  
A Cell

Endocrine cells of the pituitary gland secrete a number of hormones, and the amount of hormone released by a cell is controlled in large part by the cell's electrical activity and subsequent Ca2+ influx. Typical electrical behaviors of pituitary cells include continuous spiking and so-called pseudo-plateau bursting. It has been shown that the amplitude of Ca2+ fluctuations is greater in bursting cells, leading to the hypothesis that bursting cells release more hormone than spiking cells. In this work, we apply computer simulations to test this hypothesis. We use experimental recordings of electrical activity as input to mathematical models of Ca2+ channel activity, buffered Ca2+ diffusion, and Ca2+-driven exocytosis. To compare the efficacy of spiking and bursting on the same cell, we pharmacologically block the large-conductance potassium (BK) current from a bursting cell or add a BK current to a spiking cell via dynamic clamp. We find that bursting is generally at least as effective as spiking at evoking hormone release and is often considerably more effective, even when normalizing to Ca2+ influx. Our hybrid experimental/modeling approach confirms that adding a BK-type K+ current, which is typically associated with decreased cell activity and reduced secretion, can actually produce an increase in hormone secretion, as suggested earlier.

scholarly journals Pituitary Actions of EGF on Gonadotropins, Growth Hormone, Prolactin and Somatolactins in Grass Carp

Biology ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 279
Author(s):  
Qiongyao Hu ◽  
Qinbo Qin ◽  
Shaohua Xu ◽  
Lingling Zhou ◽  
Chuanhui Xia ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Mrna Expression ◽  
Grass Carp ◽  
Hormone Secretion ◽  
Pituitary Hormones ◽  
Vital Role ◽  
Pituitary Hormone ◽  
Pituitary Cells ◽  
Neurokinin Receptor

In mammals, epidermal growth factor (EGF) plays a vital role in both pituitary physiology and pathology. However, the functional role of EGF in the regulation of pituitary hormones has rarely reported in teleost. In our study, using primary cultured grass carp pituitary cells as an in vitro model, we examined the effects of EGF on pituitary hormone secretion and gene expression as well as the post-receptor signaling mechanisms involved. Firstly, we found that EGF significantly reduced luteinizing hormone (LHβ) mRNA expression via ErbB1 coupled to ERK1/2 pathway, but had no effect on LH release in grass carp pituitary cells. Secondly, the results showed that EGF was effective in up-regulating mRNA expression of growth hormone (GH), somatolactin α (SLα) and somatolactin β (SLβ) via ErbB1 and ErbB2 and subsequently coupled to MEK1/2/ERK1/2 and PI3K/Akt/mTOR pathways, respectively. However, EGF was not effective in GH release in pituitary cells. Thirdly, we found that EGF strongly induced pituitary prolactin (PRL) release and mRNA expression, which was mediated by ErbB1 and subsequent stimulation of MEK1/2/ERK1/2 and PI3K/Akt/mTOR pathways. Interestingly, subsequent study further found that neurokinin B (NKB) significantly suppressed EGF-induced PRL mRNA expression, which was mediated by neurokinin receptor (NK2R) and coupled to AC/cAMP/PKA signal pathway. These results suggested that EGF could differently regulate the pituitary hormones expression in grass carp pituitary cells.

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