Interleukin-1β stimulates cell proliferation in the intermediate lobe of the rat pituitary gland

1994 ◽  
Vol 140 (3) ◽  
pp. 337-341 ◽  
Author(s):  
H Stępień ◽  
G Żerek-Mełen ◽  
S Mucha ◽  
K Winczyk ◽  
J Fryczak

Abstract Interleukin-1 (IL-1) is a multifunctional monokine which possesses an impressive array of diverse actions relating to the function of the immune system. IL-1 is present and formed locally in the brain as demonstrated by biochemical and immunocytochemical methods. Various immunomodulatory and neuroendocrine effects of IL-1 have been reported, including induction of several morphological changes in the endocrine cells of experimental animals and humans. IL-1 is present in two molecular forms (IL-1α and IL-1β) that activate specific receptors for IL-1. In the present study we investigated the possible effect of recombinant human IL-1α and IL-1β and recently cloned anti-human IL-1 receptor antibody (M10) on cell proliferation in the anterior and the intermediate lobe of the pituitary gland of the rat. In vivo labelling with bromodeoxyuridine (BrdU) and immunocytochemical staining with anti-BrdU monoclonal antibody were used as a sensitive index of cell proliferation. IL-1β was found to stimulate dose-dependently (0·1–10 μg/kg body weight) incorporation of BrdU into pituitary intermediate cell nuclei, and positive correlation between the tested doses of IL-1β and BrdU-labelling index was noted (r=0·89; P<0·01). This IL-1β-induced stimulation of pituitary pars intermedia cell proliferation was receptor specific, since stimulation was blocked by anti-IL-1 receptor antibody. On the other hand, recombinant human IL-1α did not affect BrdU incorporation and the proliferation of pituitary pars intermedia cells. In addition, neither of the cytokines tested in the same experimental conditions showed any effect on the cell growth of the pituitary pars anterior. These results suggest that IL-1β may be involved in the regulation of the cell growth of the pituitary intermediate lobe in rats. Journal of Endocrinology (1994) 140, 337–341

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1817-1817 ◽  
Author(s):  
Alvin H. Schmaier ◽  
Fakhri Mahdi ◽  
Robert Sitrin

Abstract Previous studies have shown that the multiprotein kininogen (HK) and factor XII (FXII) receptor complex on endothelial cells (HUVEC) that consists of gC1qR, uPAR, and cytokeratin 1 (Blood97:2342, 99:3585) allows for prekallikrein assembly and activation for bradykinin formation (Blood 103:4554). New studies show outside-in signaling through this HUVEC receptor complex. Single chain urokinase (ScuPA) or FXII in the presence of 0.05 mM zinc ion stimulates ERK1/2 (MAPK42 and 44) in HUVEC (Blood 106:Abstract 1024Blood 106:Abstract 2005). Furthermore, cleaved HK (HKa) or peptides from the HK domain 5 cell binding region block HUVEC ERK1/2 phosphorylation. The region on uPAR that mediates this signaling is the same 22 aa sequence on uPAR domain 2 that binds ScuPA, FXII, HK, and vitronectin (JBC 279:16621). ScuPA or FXII phosphorylation of ERK1/2 is blocked by 0.1 mM PD98059, 30 nM wortmann, or 0.05 mM LY294002. Additional investigations determined if ScuPA or FXII in the presence of zinc ion stimulate Akt phosphorylation (Ser473). Both ScuPA (5–200 nM) or FXII (15–200 nM) in the presence of 0.05 mM zinc ion stimulated HUVEC Akt phosphorylation and it is blocked by 30 nM wortmann or 0.05 mM LY294002. Investigations next determined if the same region on uPAR that mediated ERK1/2 phosphorylation participated in Akt phosphorylation. Peptide LRG20 (L166-D185)or PGS20 (P176-T195) from domain 2 of uPAR or peptides HVL20 (H471-K494), HKH20 (H479-H498) or FKL20 (F459-K478) from domain 5 of HK blocked ScuPA- or FXII-induced phosphorylation of Akt (Ser473). Since uPAR does not directly interact with intracellular pathways, further investigations determined the mechanism for outside-in signaling. Studies showed that two antibodies to beta-1-integrin (Mabs 2253 and 1987) blocked ScuPA- or FXII-induced phosphorylation of Akt (Ser473). Additional investigations showed that ScuPA- (16–64 nM) or FXII- (60–240 nM) induced cell proliferation in a concentration-dependent fashion and it was blocked by peptide LRG20 of uPAR or HVL24 of HK’s domain 5. Further, cell proliferation is blocked by PD98059, wortmann, LY294002, and Mab 2253 to beta-1-integrin. Similarly, cell growth as measured by BrdU incorporation was induced by ScuPA or FXII in a concentration-dependent fashion. BrdU incorporation was blocked by peptides LRG20 and HVL24 as well as PD98059, wortmann, LY294002, and Mab 2253 to beta-1-integrin. These combined studies indicate uPAR in the kininogen multiprotein complex serves as at least one focal point for outside-in signaling after ScuPA or FXII binding. Stimulation of this receptor through beta-1-integrin leads to phosphorylation of ERK1/2 and Akt (Ser473) and induces HUVEC growth and proliferation. These investigations indicate two novel findings: first, they indicate outside-in signaling pathways for the multiprotein receptor complex for ScuPA, FXII, and HK. Second, they describe at least one pathway for the anti-angiogenic and anti-proliferative activities of HKa and its domain 5 fragments. These investigations show that the multiprotein kininogen/FXII receptor complex influences both HUVEC cellular growth and proliferation as well as intravascular proteolytic activity leading to bradykinin formation, blood pressure control and modulation of thrombosis risk (Blood 108:192).


1936 ◽  
Vol s2-78 (312) ◽  
pp. 637-651
Author(s):  
N. H. HOWES

1. The structure of the pituitary of the adult skate is described. 2. This gland shows two distinct regions of growth which can be correlated with increase of size of the animal. 3. The pars anterior can be subdivided into three regions differing by the staining reactions of their constituent cells: (a) an anterior region where deep-purple chromaphil cells are found; (b) a middle, where they are faintly basiphil; and (c) a posterior, where they are mainly acidophil. 4. It is suggested that these regions are homologous with the pars tuberalis, basiphil, and oxyphil areas respectively of the pars anterior of the mammalian pituitary. 5. The oxyphil cells show an iodine-leucobase reaction similar to that given by the oxyphil cells of the ox pituitary. 6. The ventral lobe is a completely separate structure from the pars intermedia, although it may run along the ventral surface of the latter for some distance. 7. The histology of the neuro-intermediate lobe is described.


1996 ◽  
Vol 148 (2) ◽  
pp. 193-196 ◽  
Author(s):  
T Pawełczyk ◽  
M Pawlikowski ◽  
J Kunert-Radek

Abstract The effect of TRH on cell proliferation in the anterior lobe of the pituitary is well known and documented. On the other hand, there are no data on the effects of TRH on the intermediate lobe of the pituitary gland. The aim of this study was to investigate the effect of TRH and its analogues (pGlu-His-Gly, pGlu-His-Gly-NH2) on cell proliferation in the intermediate pituitary lobe. The bromodeoxyuridine technique was used to detect the proliferating cells. It was found that TRH stimulated cell proliferation 24 h after a single injection at a dose of 100 μg/kg body weight. The TRH analogues did not exert any significant stimulatory effect either 12 h or 24 h after the injection. The second experiment was carried out to distinguish the probable mechanism of the action of TRH. The effects of TSH and prolactin (PRL) on intermediate lobe cell proliferation were examined. It was found that both PRL and TSH exerted a significant stimulatory effect 24 h after a single s.c. injection of PRL at a dose of 150 IU/kg body weight or TSH at a dose 20 IU/kg body weight. It therefore appears that the stimulatory effect of TRH on intermediate pituitary lobe cell proliferation is mediated by PRL and TSH. Journal of Endocrinology (1996) 148, 193–196


1981 ◽  
Vol 97 (3) ◽  
pp. 343-351 ◽  
Author(s):  
F.J. H. Tilders ◽  
M. Post ◽  
S. Jackson ◽  
P.J. Lowry ◽  
P. G. Smelik

Abstract. The intermediate lobe of the rat pituitary gland produces a series of peptides related to ACTH and LPH. The spontaneous and isoproterenol-stimulated release of such peptides was studied during in vitro superfusion of rat neurointermediate lobes with Krebs-Ringer medium. Products released into the superfusion medium were quantified by direct measurement or after chromatography on Sephadex G-50. ACTH bioactivity was determined by use of adrenal cortical cell suspension assay. In addition, NH2-terminal ACTH, CO2H-terminal ACTH, α-MSH and β-endorphin radioimmunoassays were used. The results show that 1. neurointermediate lobes of rats secrete spontaneously various ACTH- and LPH-related peptides in amounts proportional to the amounts in which these peptides are found in extracts of the neurointermediate lobe; 2. the β-adrenergic agonist, isoproterenol, stimulated the spontaneous release of various peptides, including α-MSH, ACTH, CLIP, glycosylated CLIP, and β-endorphin-like peptides; 3. isoproterenol induced a dose-dependent (10−9–10−7 m), parallel increase in the release of α-MSH and ACTH following similar time courses and showing indentical EC50 values (about 10−8 m). Although the spontaneous release of α-MSH and ACTH from rat neurointermediate lobes is not strictly coupled under the conditions used in this study, isoproterenol seems to affect the spontaneous release of these peptides to the same relative extent.


1977 ◽  
Vol 75 (3) ◽  
pp. 443-444 ◽  
Author(s):  
J. RYCHTER ◽  
H. STEPIEŃ

Department of Experimental Endocrinology, Institute of Endocrinology, Medical Academy of Łódź, Dr. Sterling str. 3, 91-425 Łódź, Poland (Received 31 May 1977) The secretory function of the intermediate lobe of the pituitary gland is under hypothalamic control (Howe, 1973; Hadley & Bagnara, 1975). Penny, Thody, Tilders & Smelik (1977) have suggested that the synthesis and release of melanocyte-stimulating hormone (MSH) is mediated by dopaminergic neurones which make synaptic contact with secretory cells in the pars intermedia (Björklund, Moore, Nobin & Stenevi, 1973). We have attempted to examine whether the dopaminergic mechanism is also involved in the control of the mitotic activity of the pars intermedia cells and have studied the effects of pimozide, a dopamine receptor blocker (Anden, Butcher, Corrodi, Fuxe & Ungerstedt, 1970) and 2-bromo-α-ergocriptine (bromo-criptine), a dopamine receptor agonist (Loew, Vigouret & Jaton, 1976) on the mitotic activity of the pars intermedia of the rat pituitary gland. Twenty-three


2013 ◽  
Vol 1 (02) ◽  
pp. 12-19
Author(s):  
Z. B. Khuroo

The presence of functional hypothalamo-hypophysial neurosecretory system in vertebrates has led to revise earlier views regarding the hypothalamus-pituitary relationship. The hypothalamo-neurohypophysial system which consists of hypothalamic nuclei, their axonal fibres forming tractus preoptico-hypophyses and the neurohypophysis) works as a morphological as well as a physiological connection between the hypothalamus and the pituitary gland. In fishes, fibres from the neurosecretory hypothalamic nuclei terminate in the neurohypophysis, which remains inter digitized with the adenohypophysis and provides a very close association between the neurosecretory fibres and pars intermedia of the pituitary gland forming a neuro-intermediate lobe. Hypothalamo-Neurosecretory complex of Xenentodon cancila consists of Nucleus Pre-opticus (NPO), Nucleus Lateralis Tuberis (NLT) and their axonal tracts. NPO is a paired structure situated on either side of the third ventricle anterodorsal to the optic chiasma. NPO is divisible into a dorsal Pars Magnocellularis (PMC) consisting of large neurosecretory cells and Pars Parvocellularis (PPC) formed of smaller neurons. Neurons of PMC and PPC contribute beaded axons to form neurohypophysial tract. Herring bodies are seen in the anterior as well as posterior neurohypophysis.


1989 ◽  
Vol 120 (3) ◽  
pp. 525-NP ◽  
Author(s):  
P. J. Coates ◽  
I. Doniach ◽  
J. M. P. Holly ◽  
L. H. Rees

ABSTRACT Immunocytochemistry, radioimmunoassay and high-performance liquid chromatography (HPLC) techniques have been used in combination to investigate the presence of immunoreactive (ir)-α-MSH in the normal human pituitary gland, and to investigate the possible origin of these cells from the fetal pars intermedia. Two separate antisera to α-MSH were employed in immunocytochemistry to distinguish between authentic α-MSH and the desacetyl form. Only desacetyl α-MSH was detected in the pituitary gland of fetal and adult man, in both the pars (zona) intermedia and the pars anterior. In the fetus, a large proportion of the ACTH-containing cells of the anterior lobe also contained ir-α-MSH, while ir-α-MSH containing cells were more sparse in adults. Radioimmunoassay of acid extracts of adult pituitary tissue showed α-MSH levels representing less than 0·05% of the ACTH content of the gland. HPLC analysis of these extracts confirmed that only the desacetyl form was present. These results suggest that α-MSH peptides are synthesized by anterior lobe cells of the human pituitary gland, which are not derived from the fetal pars intermedia. Possible regulatory mechanisms affecting cells which contain ir-α-MSH are discussed, and by comparison with the intermediate lobe of other species it is concluded that there is little evidence for a true intermediate lobe in the human pituitary gland. Journal of Endocrinology (1989) 120, 525–530


1983 ◽  
Vol 99 (2) ◽  
pp. 239-243 ◽  
Author(s):  
Irina Pollard

An ultrastructural study is described which relates cellular activity in the intermediate lobe of the pituitary gland with circulating levels of corticosterone. Exposure of male CSF rats to a signalled, unpredictable 60-day stress regimen induced intense secretory activity in all cells of the pars intermedia for the first 5 days of stressing, and thereafter secretory activity reverted back to the control condition. Blood corticosterone levels showed an initial extreme increase lasting for the first 5 days of exposure to the stress before gradually falling to re-establish a new stable level of secretion by 40 days. The possible involvement of the intermediate lobe in emotional or psychological stress when corticosterone levels are high is discussed.


2020 ◽  
Vol 26 ◽  
Author(s):  
Yuying Qi ◽  
Chaoying Song ◽  
Jiali Zhang ◽  
Chong Guo ◽  
Chengfu Yuan

Background: Long non-coding RNA (LncRNAs), with the length over 200 nucleotides, originate from intergenic, antisense, or promoter-proximal regions, is a large family of RNAs that lack coding capacity. Emerging evidences illustrated that LncRNAs played significant roles in a variety of cellular functions and biological processes in profuse human diseases, especially in cancers. Cancer susceptibility candidate 9 (CASC9), as a member of the LncRNAs group, was firstly found its oncogenic function in esophageal cancer. In following recent studies, a growing amount of human malignancies are verified to be correlated with CASC9, most of which are derived from the squamous epithelium tissue. This present review attempts to highlight the latest insights into the expression, functional roles, and molecular mechanisms of CASC9 in different human malignancies. Methods: In this review, the latest findings related to the pathophysiological processes of CASC9 in human cancers were summarized and analyzed, the associated studies were collected in systematically retrieval of PubMed used lncRNA and CASA9 as keywords. Results: CASC9 expression is identified to be aberrantly elevated in a variety of malignancies. The over-expression of CASC9 has been suggested to accelerate cell proliferation, migration, cell growth and drug resistance of cancer cells, while depress cell apoptosis, revealing its role as an oncogene. Moreover, the current review demonstrated CASC9 closely relates to neoplastic transformation of squamous epithelial cells and squamous metaplasia in non-squamous epithelial tissues. Finally, we discuss the limitations and tremendous diagnostic/therapeutic potential of CASC9 in various human cancers. Results: CASC9 expression is identified to be aberrantly elevated in a variety of malignancies. The over-expression of CASC9 has been suggested to accelerate cell proliferation, migration, cell growth and drug resistance of cancer cells, while depress cell apoptosis, revealing its role as an oncogene. Moreover, the current review demonstrated CASC9 closely relates to neoplastic transformation of squamous epithelial cells and squamous metaplasia in non-squamous epithelial tissues. Finally, we discuss the limitations and tremendous diagnostic/therapeutic potential of CASC9 in various human cancers. Conclusion: Long non-coding RNACASC9 likely served as useful disease biomarkers or therapy targets that could effectively apply in treatment of different kinds of cancers.


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