Journal of Molecular Endocrinology
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Molecular mechanisms of somatostatin receptor trafficking The neuropeptide somatostatin (SRIF) is an important modulator of neurotransmission in the central nervous system and acts as a potent inhibitor of hormone and exocrine secretion. In addition, SRIF regulates cell proliferation in normal and tumorous tissues. The six somatostatin receptor subtypes (sst1, sst2A, sst2B, sst3, sst4, and sst5), which belong to the G protein-coupled receptor (GPCR) family, share a common molecular topology: a hydrophobic core of seven transmembrane-spanning α-helices, three intracellular loops, three extracellular loops, an amino-terminus outside the cell, and a carboxyl-terminus inside the cell. For most of the GPCRs, intracytosolic sequences, and more particularly the C-terminus, are believed to interact with proteins that are mandatory for either exporting neosynthesized receptor, anchoring receptor at the plasma membrane, internalization, recycling, or degradation after ligand binding. Accordingly, most of the SRIF receptors can traffic not onlyin vitro within different cell types but alsoin vivo . A picture of the pathways and proteins involved in these processes is beginning to emerge.
Journal of Molecular Endocrinology - Tập 48 Số 1 - Trang R1-R12 - 2012
Multiple actions of the chemokine stromal cell-derived factor-1α on neuronal activity The chemokine SDF-1α and its cognate receptor CXCR4 are expressed in several neuronal populations. This review focuses on our current knowledge about the actions of this chemokine on neuronal excitability, through CXCR4 or other yet unknown pathways. In various neuronal populations (CA1 neurons of the hippocampus, granular and Purkinje cells of the cerebellum, melanin-concentrating hormone neurons of the lateral hypothalamus, vasopressinergic neurons of the supraoptic and the paraventricular nucleus of the hypothalamus, and dopaminergic neurons of the substantia nigra), SDF-1α can modulate the activity of neurons by multiple regulatory pathways including and often combining: (i) modulation of voltage-dependent channels (sodium, potassium, and calcium), (ii) activation of the G-protein-activated inward rectifier potassium current, and (iii) increase in neurotransmitter release (gamma-amino butyric acid (GABA), glutamate, and dopamine), often through Ca-dependent mechanisms. The possible mechanisms underlying these effects and their consequences in terms of modulation of neuroendocrine systems and physiopathology are discussed.
Journal of Molecular Endocrinology - Tập 38 Số 3 - Trang 365-376 - 2007
Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays The reverse transcription polymerase chain reaction (RT-PCR) is the most sensitive method for the detection of low-abundance mRNA, often obtained from limited tissue samples. However, it is a complex technique, there are substantial problems associated with its true sensitivity, reproducibility and specificity and, as a quantitative method, it suffers from the problems inherent in PCR. The recent introduction of fluorescence-based kinetic RT-PCR procedures significantly simplifies the process of producing reproducible quantification of mRNAs and promises to overcome these limitations. Nevertheless, their successful application depends on a clear understanding of the practical problems, and careful experimental design, application and validation remain essential for accurate quantitative measurements of transcription. This review discusses the technical aspects involved, contrasts conventional and kinetic RT-PCR methods for quantitating gene expression and compares the different kinetic RT-PCR systems. It illustrates the usefulness of these assays by demonstrating the significantly different levels of transcription between individuals of the housekeeping gene family, glyceraldehyde-3-phosphate-dehydrogenase (GAPDH).
Journal of Molecular Endocrinology - Tập 25 Số 2 - Trang 169-193 - 2000
Growth hormone induces tyrosine phosphorylation but does not alter insulin-like growth factor-I gene expression in human IM9 lymphocytes ABSTRACT
GH induces hepatic IGF-I synthesis by increasing transcription of its gene. IGF-I is synthesized, however, in many other tissues where the effect of GH on its gene expression is less well characterized. IGF-I and GH are produced by human lymphocytes and may function as autocrine regulators of lymphoproliferation. We have therefore used the human IM9 lymphocyte cell line to (A) define the IGF-I gene transcripts expressed and (B) investigate the effect of GH on early (protein tyrosine phosphorylation) and late (changes in IGF-I mRNA levels) events in intracellular signal transduction. Multiple IGF-I mRNA species, ranging in size from 0·9 to 5·8 kb, were detected by Northern hybridization of poly(A)+ mRNA from IM9 cells. The human IGF-I gene contains at least six exons and alternative splicing produces a number of transcripts. Solution hybridization with exon-specific riboprobes and amplification by PCR using exon-specific primers revealed that multiple transcripts were expressed in IM9 cells, and that exon 2 was the dominant leader exon.
Treatment of IM9 cells with 200 ng recombinant human (rh)GH/ml led to the specific tyrosine phosphorylation of three intracellular proteins (93, 120 and 134 kDa), which are involved in the initial signalling of the GH transduction pathway. However a solution hybridization assay using the IGF-IA specific riboprobe on IM9 cell RNA from similar experiments revealed that GH treatment did not change IGF-I gene expression.
This study has demonstrated (A) that the IGF-I gene is expressed in human IM9 lymphocytes, (B) that in contrast to other human tissue, exon 2 is the major leader exon, and (C) that rhGH induces tyrosine phosphorylation of 93, 120 and 134 kDa proteins but does not alter IGF-I gene expression. The IM9 cell may form an important model to investigate a GH transduction pathway not coupled to the IGF-I gene.
Journal of Molecular Endocrinology - Tập 13 Số 2 - Trang 127-136 - 1994
Developmental and tissue-regulated expression of IGF-I and IGF-II mRNAs in Sparus aurata ABSTRACT
Recent studies have shown that homologues of the mammalian IGF-I and -II genes are also found in teleosts. We report here the cDNAs coding for IGF-I and IGF-II cloned from the gilthead seabream, Sparus aurata . Sequence comparisons revealed that both IGFs have been well conserved among teleosts, although Sparus IGF-I is shorter by three amino acid residues due to truncated B-and C-domains. Using the cloned cDNAs as probes, the relative expression of IGF-I and IGF-II mRNAs were assayed in different Sparus tissues. Sparus liver clearly contained the highest level of IGF-I mRNA while relatively high levels of IGF-II mRNA were found in liver, heart and gill using the ribonuclease protection assay. After GH administration the amount of IGF-I mRNA was increased by 220% in liver but no changes in IGF-II mRNA levels were detected in any tissue. We also assayed the expression of IGF-I and IGF-II in Sparus during early development. The IGF-II mRNA level was highest in larva 1 day after hatching and decreased thereafter. In contrast, IGF-I mRNA was detected in 1-day-old larva but there was an increase in expression in 12- and 16-day-old larva. These results demonstrated that the expression of IGF-I and IGF-II is highly regulated in teleosts and suggest that they play distinct roles during growth and development.
Journal of Molecular Endocrinology - Tập 16 Số 2 - Trang 123-132 - 1996
Effect of nuclear export inhibition on estrogen receptor regulation in breast cancer cells
Journal of Molecular Endocrinology - Tập 39 Số 2 - Trang 105-118 - 2007
Adipokines in the skeleton: influence on cartilage function and joint degenerative diseases The discovery of leptin in 1994 marked the beginning of a new understanding about white adipose tissue (WAT) and modified a static vision of this tissue which was viewed up to the end of the 20th century as an inert tissue, devoted to body protection from heat loss and to passively storing energy. The identification of the product of the gene obese accentuated the role of adipose tissue in the physiopathology of obesity-linked diseases, and led to the discovery of various adipokines, many of a pro-inflammatory nature. It has become progressively manifest that WAT-derived adipokines can now be considered as the fulcrum between obesity-related environmental causes, such as nutrition and lifestyle, and the biochemical shifts that lead to metabolic syndrome, inflammatory and/or autoimmune conditions, and rheumatic diseases. Herein, we review recent adipokine research, with particular emphasis to the role of leptin, adiponectin, resistin, and visfatin in chondrocyte function and skeleton, as well as in inflammatory and degenerative cartilage joint diseases.
Journal of Molecular Endocrinology - Tập 43 Số 1 - Trang 11-18 - 2009
Multiple forms of parathyroid hormone-like proteins in a human tumour ABSTRACT
The extensive chromatographic characterization of four parathyroid hormone (PTH)-like proteins in a human bronchial carcinoid tumour associated with humoral hypercalcaemia and severe osteitis fibrosa is described. PTH-like bioactivity was detected in acetic acid extracts of the tumour using an in-vitro osteosarcoma cell bioassay. The active tumour proteins were positively charged at physiological pH and had apparent M r of approximately 29 000, 16 000, 4000–9000 and < 4000. The proteins were immunologically distinct from PTH, but each stimulated PTH-sensitive adenylate cyclase in cultured osteoblastic cells. There was no evidence of PTH gene expression by the tumour. These proteins represent different molecular forms of PTH-related protein.
Journal of Molecular Endocrinology - Tập 2 Số 1 - Trang 11-20 - 1989
FSH receptor gene expression during ovarian follicle development in sheep ABSTRACT
A key question in elucidating the role of FSH in ovarian function is to determine when during follicular growth the FSH receptor first appears. The aim of this study was to examine the site and time of FSH receptor gene expression during early follicular growth. This study was carried out on ovaries of adult sheep during the luteal and prostaglandin-induced follicular phase of the oestrous cycle and also on ovaries of fetal sheep at 90, 100, 120 and 135 days of gestation (term=day 147).
Using reverse transcription-PCR and a set of PCR primers spanning exons 8/9/10, two partial FSH receptor cDNAs (500 and 310 bp) were isolated from adult sheep ovary. It was shown by sequencing that exon 8 was deleted in the 310 bp cDNA, implying that this was part of an alternatively spliced FSH receptor transcript. Using RNA in situ hybridisation on ovaries of adult sheep, FSH receptor mRNA was observed in granulosa cells of early preantral follicles with one to two cell layers and it was seen that gene expression continued throughout folliculogenesis into advanced stages of atresia. Moreover, in the fetus, FSH receptor gene expression was detected in follicles with two or more layers of granulosa cells in ovaries taken at 100, 120 and 135 days of gestation.
These results suggest that the FSH receptor gene is expressed after the granulosa cells of a folllicle have begun to divide but not during the earliest stages of follicle growth, namely the transformation of a primordial follicle to a primary follicle.
Journal of Molecular Endocrinology - Tập 15 Số 3 - Trang 273-281 - 1995
Gene expression profiling identifies liver X receptor alpha as an estrogen-regulated gene in mouse adipose tissue Estrogens reduce adipose tissue mass in both humans and animals. The molecular mechanisms for this effect are, however, not well characterized. We took a gene expression profiling approach to study the direct effects of estrogen on mouse white adipose tissue (WAT). Female ovariectomized mice were treated for 10, 24 and 48 h with 17beta-estradiol or vehicle. RNA was extracted from gonadal fat and hybridized to Affymetrix MG-U74Av2 arrays. 17beta-Estradiol was shown to decrease mRNA expression of liver X receptor (LXR) alpha after 10 h of treatment compared with the vehicle control. The expression of several LXRalpha target genes, such as sterol regulatory element-binding protein 1c, apolipoprotein E, phospholipid transfer protein, ATP-binding cassette A1 and ATP-binding cassette G1, was similarly decreased. We furthermore identified a 1.5 kb LXRalpha promoter fragment that is negatively regulated by estrogen. Several genes involved in lipogenesis and lipolysis were identified as novel targets that could mediate estrogenic effects on adipose tissue. Finally, we show that ERalpha is the main estrogen receptor expressed in mouse white adipose tissue (WAT) with mRNA levels several hundred times higher than those of ERbeta mRNA.
Journal of Molecular Endocrinology - Tập 32 Số 3 - Trang 879-892 - 2004
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