Cholecystokinin and the hormone concept

The birth certificate for endocrinology was Bayliss’ and Starling’s demonstration in 1902 that regulation of bodily functions is not only neuronal but also due to blood-borne messengers. Starling named these messengers hormones. Since then transport via blood has defined hormones. This definition, however, may be too narrow. Thus, today we know that several peptide hormones are not only produced and released to blood from endocrine cells but also released from neurons, myocytes, immune cells, endothelial cells, spermatogenic cells, fat cells, etc. And they are often secreted in cell-specific molecular forms with more or less different spectra of activity. The present review depicts this development with the story about cholecystokinin which was discovered in 1928 as a hormone and still in 1976 was conceived as a single blood-borne peptide. Today’s multifaceted picture of cholecystokinin suggests that time may be ripe for expansion of the hormone concept to all messenger molecules, which activate their target cells – irrespective of their road to the target (endocrine, neurocrine, neuronal, paracrine, autocrine, etc.) and irrespective of their kind of activity as classical hormone, growth factor, neurotransmitter, adipokine, cytokine, myokine, or fertility factor.

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MicroRNA-Regulated Rickettsial Invasion into Host Endothelium via Fibroblast Growth Factor 2 and Its Receptor FGFR1

Cells ◽

10.3390/cells7120240 ◽

2018 ◽

Vol 7 (12) ◽

pp. 240 ◽

Cited By ~ 5

Author(s):

Abha Sahni ◽

Hema Narra ◽

Jignesh Patel ◽

Sanjeev Sahni

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Host Cells ◽

Microvascular Endothelial Cells ◽

Target Cells ◽

Fibroblast Growth ◽

Wide Range ◽

Microvascular Endothelial

Microvascular endothelial cells (ECs) represent the primary target cells during human rickettsioses and respond to infection via the activation of immediate–early signaling cascades and the resultant induction of gene expression. As small noncoding RNAs dispersed throughout the genome, microRNAs (miRNAs) regulate gene expression post-transcriptionally to govern a wide range of biological processes. Based on our recent findings demonstrating the involvement of fibroblast growth factor receptor 1 (FGFR1) in facilitating rickettsial invasion into host cells and published reports suggesting miR-424 and miR-503 as regulators of FGF2/FGFR1, we measured the expression of miR-424 and miR-503 during R. conorii infection of human dermal microvascular endothelial cells (HMECs). Our results revealed a significant decrease in miR-424 and miR-503 expression in apparent correlation with increased expression of FGF2 and FGFR1. Considering the established phenomenon of endothelial heterogeneity and pulmonary and cerebral edema as the prominent pathogenic features of rickettsial infections, and significant pathogen burden in the lungs and brain in established mouse models of disease, we next quantified miR-424 and miR-503 expression in pulmonary and cerebral microvascular ECs. Again, R. conorii infection dramatically downregulated both miRNAs in these tissue-specific ECs as early as 30 min post-infection in correlation with higher FGF2/FGFR1 expression. Changes in the expression of both miRNAs and FGF2/FGFR1 were next confirmed in a mouse model of R. conorii infection. Furthermore, miR-424 overexpression via transfection of a mimic into host ECs reduced the expression of FGF2/FGFR1 and gave a corresponding decrease in R. conorii invasion, while an inhibitor of miR-424 had the expected opposite effect. Together, these findings implicate the rickettsial manipulation of host gene expression via regulatory miRNAs to ensure efficient cellular entry as the critical requirement to establish intracellular infection.

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142 Isolation of the Quail Spermatogonia

Reproduction Fertility and Development ◽

10.1071/rdv30n1ab142 ◽

2018 ◽

Vol 30 (1) ◽

pp. 211

Author(s):

E. R. Mennibaeva ◽

N. A. Volkova ◽

E. K. Tomgorova ◽

L. A. Volkova ◽

V. A. Bagirov ◽

...

Keyword(s):

Growth Factor ◽

Sertoli Cells ◽

Recombinant Dna ◽

Initial Study ◽

Seminiferous Tubules ◽

Target Cells ◽

Spermatogenic Cells ◽

Russian Science ◽

Epidermal Growth ◽

The Individual

Spermatogonia are testicular stem cells, the precursors of male sex cells. They are target cells for introduction of recombinant DNA and suitable for creation of cryobanks to preserve biological materials. The aim of our research was to optimize the individual stages culturing quail spermatogonia. In an initial study, dynamics of change in the composition of spermatogenic cells in the seminiferous tubules were assessed histologically, at weekly intervals from 1 week to 1.5 months of age. Thereafter, spermatogonia were isolated from quail testes. Disaggregation of the testis tissue was carried out by consecutive enzymatic treatment in 0.25% trypsin and 0.1% collagenase solution. Purification of spermatogonia from other types of spermatogenic cells was conducted by separation of the cells by adhesion. The duration and conditions of cultivation of spermatogenic cells were selected experimentally. Cultivation of spermatogonia was performed on feeder layers, including quail primary Sertoli cells, STO cell line, and transplanted porcine Sertoli cells. Growth medium for culturing spermatogonia was DMEM HG medium supplemented with 5% FCS, 2 mM α-glutamine, MEM (10 μL mL−1), antibiotic (100×), insulin-transferrin-selenium (ITS, 10 μL mL−1), 2-mercaptoethanol (5 × 10−5 M), albumin (5 mg mL−1), epidermal growth factor (EGF, 20 ng mL−1), basic fibroblast growth factor (bFGF, 10 ng mL−1), and leukemia inhibitory factor (LIF, 2 ng mL−1). For identification of spermatogonia colonies, SSEA-1 antibodies were used. The maximum number of spermatogonia in seminiferous tubules of quail occurred at 3 weeks of age; there were mainly spermatogonia and Sertoli cells at this time. The percentage of spermatogonia from the total number of spermatogenic cells in the seminiferous tubule reached 76 ± 2%. In view of this, spermatogonia were isolated from the testes of 2-week-old quail. Spermatogenic cells were cultured for 24 h, after which the supernatant with unattached cells, mainly spermatogonia, was transferred to a new dish and cultured. Maximum homogeneity of the cell population was detected by dividing the cells by 3-fold transfer of the cell supernatant at an interval of 24 h; the proportion of spermatogonia in the suspension reached 88%. Quail Sertoli cells were the optimal feeder layer for cultivation of quail spermatogonia. Formation of spermatogonia colonies was observed on Day 5 to 7 of cultures, and their identity confirmed by immunohistochemical staining for SSEA-1. The study was supported by the Russian Science Foundation within Project no.16-16-04104.

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Regulation of the vascular endothelial growth factor (VEGF) receptor Flk-1/KDR by estradiol through VEGF in uterus

Journal of Endocrinology ◽

10.1677/joe.1.06184 ◽

2006 ◽

Vol 188 (1) ◽

pp. 91-99 ◽

Cited By ~ 59

Author(s):

M A J Hervé ◽

G Meduri ◽

F G Petit ◽

T S Domet ◽

G Lazennec ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Growth Factor ◽

Receptor Expression ◽

Maximal Response ◽

Target Cells ◽

Vegf Receptor ◽

Dependent Manner ◽

Vascular Endothelial ◽

Endothelial Growth Factor

The induction of vascular endothelial growth factor (VEGF) expression by 17β-estradiol (E2) in many target cells, including epithelial cells, fibroblasts and smooth muscle cells, suggests a role for this hormone in the modulation of angiogenesis and vascular permeability. We have already described a cyclic increase in Flk-1/KDR-expressing capillaries in the human endometrium during the proliferative and mid-secretory phases, strongly suggestive of an E2 effect on Flk-1/KDR expression in the endometrial capillaries. However, it is unclear whether these processes are due to a direct effect of E2 on endothelial cells. Using immunohistochemistry, we report an increase in Flk-1/KDR expression in endometrial capillaries of ovariectomized mice treated with E2, or both E2 and progesterone. This process is mediated through estrogen receptor (ER) activation. In vitro experiments using quantitative RT-PCR analysis demonstrate that Flk-1/KDR expression was not regulated by E2 in human endothelial cells from the microcirculation (HMEC-1) or macrocirculation (HUVEC), even in endothelial cells overexpressing ERα or ERβ after ER-mediated adenovirus infection. In contrast, Flk-1/KDR expression was up-regulated by VEGF itself, in a time- and dose-dependent manner, with the maximal response at 10 ng/ml. Thus, we suggest that E2 up-regulates Flk-1/KDR expression in vivo in endothelial cells mainly through the modulation of VEGF by a paracrine mechanism. It is currently unknown whether or not the endothelial origin might account for differences in the E2-modulation of VEGF receptor expression, particularly in relation to the vascular bed of sex steroid-responsive tissues.

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Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation

Development ◽

10.1242/dev.114.2.521 ◽

1992 ◽

Vol 114 (2) ◽

pp. 521-532 ◽

Cited By ~ 22

Author(s):

G. Breier ◽

U. Albrecht ◽

S. Sterrer ◽

W. Risau

Keyword(s):

Molecular Weight ◽

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Endothelial Cell ◽

Growth Factor ◽

Brain Development ◽

Molecular Forms ◽

Endothelial Cell Proliferation ◽

Vascular Endothelial ◽

Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is a secreted angiogenic mitogen whose target cell specificity appears to be restricted to vascular endothelial cells. Such factors are likely candidates for regulatory molecules involved in endothelial growth control. We have characterized the murine VEGF gene and have analysed its expression pattern in embryogenesis, particularly during brain angiogenesis. Analysis of cDNA clones predicted the existence of three molecular forms of VEGF which differ in size due to heterogeneity at the carboxy terminus of the protein. The predicted mature proteins consist of 120, 164 or 188 amino acid residues. Homodimers of the two lower molecular weight forms, but not of the higher molecular weight form, were secreted by COS cells transfected with the corresponding cDNAs and were equally potent in stimulating the growth of endothelial cells. During brain development, VEGF transcript levels were abundant in the ventricular neuroectoderm of embryonic and postnatal brain when endothelial cells proliferate rapidly but were reduced in the adult when endothelial cell proliferation has ceased. The temporal and spatial expression of VEGF is consistent with the hypothesis that VEGF is synthesized and released by the ventricular neuroectoderm and may induce the ingrowth of capillaries from the perineural vascular plexus. In addition to the transient expression during brain development, a persistent expression of VEGF was observed in epithelial cells adjacent to fenestrated endothelium, e.g. in choroid plexus and in kidney glomeruli. The data are consistent with a role of VEGF as a multifunctional regulator of endothelial cell growth and differentiation.

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Cell-specific localization of insulin-like growth factor binding protein mRNAs in rat liver

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2000.278.3.g447 ◽

2000 ◽

Vol 278 (3) ◽

pp. G447-G457 ◽

Cited By ~ 34

Author(s):

Ellen M. Zimmermann ◽

Lina Li ◽

Eileen C. Hoyt ◽

Jolanta B. Pucilowska ◽

Steven Lichtman ◽

...

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Liver Cell ◽

Target Cells ◽

Insulin Like Growth Factor ◽

Specific Expression ◽

Isolated Rat Hepatocytes ◽

Gh Receptor ◽

Igf I ◽

Igf Receptor

The liver is a major source of circulating insulin-like growth factor I (IGF-I), and it also synthesizes several classes of IGF binding proteins (IGFBPs). Synthesis of IGF-I and IGFBPs is regulated by hormones, growth factors, and cytokines. They are nutritionally regulated and expressed in developmentally specific patterns. To gain insight into cellular regulatory mechanisms that determine hepatic synthesis of IGF-I and IGFBPs and to identify potential target cells for IGF-I within the liver, we studied the cellular sites of synthesis of IGF-I, IGF receptor, growth hormone (GH) receptor, and IGFBPs in freshly isolated rat hepatocytes, endothelial cells, and Kupffer cells. We also localized cellular sites of IGFBP synthesis by in situ hybridization histochemistry. Western ligand and immunoblot analyses were used to determine IGFBP secretion by isolated cells. Two IGF-I mRNA subtypes with different 5′ ends (class 1 and class 2) were detected in all isolated liver cell preparations. Type 1 IGF receptor mRNA was detected in endothelial cells, indicating that these cells are a local target for IGF actions in liver. GH receptor was expressed in all cell preparations, consistent with GH regulation of IGF-I and IGFBP synthesis in multiple liver cell types. The IGFBPs expressed striking cell-specific expression. IGFBP-1 was synthesized only in hepatocytes, and IGFBP-3 was expressed in Kupffer and endothelial cells. IGFBP-4 was expressed at high levels in hepatocytes and at low levels in Kupffer and endothelial cells. Cell-specific expression of distinct IGFBPs in the liver provides the potential for cell-specific regulation of hepatic and endocrine actions of IGF-I.

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