scholarly journals A novel human GnRH receptor homolog gene: abundant and wide tissue distribution of the antisense transcript

1999 ◽  
Vol 162 (1) ◽  
pp. 117-126 ◽  
Author(s):  
R Millar ◽  
D Conklin ◽  
C Lofton-Day ◽  
E Hutchinson ◽  
B Troskie ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Gnrh Receptor ◽  
Receptor Subtypes ◽  
Type I ◽  
Type Ii ◽  
Antisense Transcripts ◽  
Antisense Orientation ◽  
Wide Range ◽  
Putative Intron ◽  
Intron 2

Gonadotropin releasing hormone (GnRH) regulates the reproductive system through a specific G-protein-coupled receptor (GPCR) in pituitary gonadotropes. The existence of two (or more) forms of GnRH in most vertebrates suggested the existence of GnRH receptor subtypes (I and II). Using sequence information for extracellular loop 3 of a putative Type II GnRH receptor from a reptile species, we have looked for a Type II GnRH receptor gene in the human genome EST (expressed sequence tag) database. A homolog was identified which has 45% and 41% amino acid identity with exons 2 and 3 of the known human GnRH pituitary receptor (designated Type I) and much lower homology with all other GPCRs. A total of 27 contiguous ESTs was found and comprised a continuous sequence of 1642 nucleotides. The EST sequences were confirmed in the cloned human gene and in PCR products of cDNA from several tissues. All EST transcripts detected were in the antisense orientation with respect to the novel GnRH receptor sequence and were highly expressed in a wide range of human brain and peripheral tissues. PCR of cDNA from a wide range of tissues revealed that intronic sequence equivalent to intron 2 of the Type I GnRH receptor was retained. The failure to splice out putative intron sequences in transcripts which spanned exon-intron boundaries is expected in antisense transcripts, as candidate donor and acceptor sites were only present in the gene when transcribed in the orientation encoding the GnRH receptor homolog. No transcripts extended 5' to the sequence corresponding to intron 2 of the Type I GnRH as the antisense transcripts terminated in poly A due to the presence of a polyadenylation signal sequence in the putative intron 2 when transcribed in the antisense orientation. These findings suggest that a Type II GnRH receptor gene has arisen during vertebrate evolution and is also present in the human. However, the receptor may have become vestigial in the human, possibly due to the abundant and universal tissue transcription of the opposite DNA strand to produce antisense RNA.

scholarly journals Type II gonadotrophin-releasing hormone (GnRH-II) in reproductive biology

Reproduction ◽  
2003 ◽  
pp. 271-278 ◽  
Author(s):  
AJ Pawson ◽  
K Morgan ◽  
SR Maudsley ◽  
RP Millar
Keyword(s):  
Receptor Gene ◽  
Gnrh Receptor ◽  
Specific Gene ◽  
Type I ◽  
Type Ii ◽  
Releasing Hormone ◽  
Human Type ◽  
Gnrh Receptors ◽  
Gonadotrophin Releasing Hormone ◽  
Ligand Precursors

Humans may be particularly unusual with respect to the gonadotrophin-releasing hormone (GnRH) control of their reproductive axis in that they possess two distinct GnRH precursor genes, on chromosomes 8p11-p21 and 20p13, but only one conventional GnRH receptor subtype (type I GnRH receptor) encoded within the genome, on chromosome 4. A disrupted human type II GnRH receptor gene homologue is present on chromosome 1q12. The genes encoding GnRH ligand precursors and GnRH receptors have now been characterized in a broad range of vertebrate species, including fish, amphibians and mammals. Ligand precursors and receptors can be categorized into three phylogenetic families. Members of each family exist in primitive vertebrates, whereas mammals exhibit selective loss of ligand precursor and receptor genes. One interpretation of these findings is that each ligand-cognate receptor family may have evolved to fulfil a separate function in reproductive physiology and that species-specific gene inactivation, modification or loss may have occurred during evolution when particular roles have become obsolete or subject to regulation by a different biochemical pathway. Evidence in support of this concept is available following the characterization of the chromosomal loci encoding the human type II GnRH receptor homologue, a rat type II GnRH receptor gene remnant (on rat chromosome 18) and a mouse type II GnRH ligand precursor gene remnant (on mouse chromosome 2). Whether type I GnRH and type II GnRH peptides elicit different signalling responses in humans by activation of the type I GnRH receptor in a cell type-specific fashion remains to be shown. Recent structure-function studies of GnRH ligands and GnRH receptors and their expression patterns in different tissues add further intrigue to this hypothesis by indicating novel roles for GnRH such as neuromodulation of reproductive function and direct regulation of peripheral reproductive tissues. Surprises concerning the complexities of GnRH ligand and receptor function in reproductive endocrinology should continue to emerge in the future.

Adrenal steroid receptor binding in spleen and thymus after stress or dexamethasone.

1990 ◽  
Vol 259 (3) ◽  
pp. E405 ◽  
Author(s):  
A H Miller ◽  
R L Spencer ◽  
M Stein ◽  
B S McEwen
Keyword(s):  
Receptor Binding ◽  
Steroid Receptor ◽  
Receptor Activation ◽  
Receptor Subtypes ◽  
Type I ◽  
Type Ii ◽  
Adrenal Steroid ◽  
Immune Tissues ◽  
Intact Rats

Type I and II adrenal steroid receptor binding was measured in spleen and thymus of adrenalectomized (ADX) rats and intact rats at basal levels of corticosterone after 1 h of restraint stress or after exogenous administration of dexamethasone (DEX). Concurrent receptor determinations were made in the hippocampus and pituitary. Receptor binding measures in immune tissues and pituitary were less responsive to varying levels of endogenous hormones than binding measures in hippocampus. Compared with ADX rats, type I binding in spleen and pituitary of intact rats at basal levels of corticosterone was unchanged, whereas type I binding in the hippocampus was significantly decreased. Furthermore, despite peak levels of corticosterone, type II binding in spleen, thymus, and pituitary of stressed rats was also unchanged, whereas type II binding in the hippocampus of stressed animals was significantly lower. In contrast, DEX, a well-known immunosuppressant, reduced type II binding in immune tissues more than in the hippocampus. Because a decrease in receptor binding measured in vitro may reflect receptor activation in vivo, these results suggest that there may be considerable heterogeneity in the degree of activation of adrenal steroid receptor subtypes in immune, pituitary, and hippocampal tissue by endogenous and exogenous glucocorticoids.

scholarly journals Cancer Biology and Prevention in Diabetes

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1380 ◽  
Author(s):  
Swayam Prakash Srivastava ◽  
Julie E. Goodwin
Keyword(s):  
Type Ii Diabetes ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Type I Diabetes ◽  
Type I ◽  
Type Ii ◽  
Mesenchymal Transition ◽  
Wide Range ◽  
Risk Of Cancer

The available evidence suggests a complex relationship between diabetes and cancer. Epidemiological data suggest a positive correlation, however, in certain types of cancer, a more complex picture emerges, such as in some site-specific cancers being specific to type I diabetes but not to type II diabetes. Reports share common and differential mechanisms which affect the relationship between diabetes and cancer. We discuss the use of antidiabetic drugs in a wide range of cancer therapy and cancer therapeutics in the development of hyperglycemia, especially antineoplastic drugs which often induce hyperglycemia by targeting insulin/IGF-1 signaling. Similarly, dipeptidyl peptidase 4 (DPP-4), a well-known target in type II diabetes mellitus, has differential effects on cancer types. Past studies suggest a protective role of DPP-4 inhibitors, but recent studies show that DPP-4 inhibition induces cancer metastasis. Moreover, molecular pathological mechanisms of cancer in diabetes are currently largely unclear. The cancer-causing mechanisms in diabetes have been shown to be complex, including excessive ROS-formation, destruction of essential biomolecules, chronic inflammation, and impaired healing phenomena, collectively leading to carcinogenesis in diabetic conditions. Diabetes-associated epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndMT) contribute to cancer-associated fibroblast (CAF) formation in tumors, allowing the epithelium and endothelium to enable tumor cell extravasation. In this review, we discuss the risk of cancer associated with anti-diabetic therapies, including DPP-4 inhibitors and SGLT2 inhibitors, and the role of catechol-o-methyltransferase (COMT), AMPK, and cell-specific glucocorticoid receptors in cancer biology. We explore possible mechanistic links between diabetes and cancer biology and discuss new therapeutic approaches.

scholarly journals Rate constants rather than biochemical mechanism determine behaviour of genetic clocks

2008 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Emery Conrad ◽  
Avraham E Mayo ◽  
Alexander J Ninfa ◽  
Daniel B Forger
Keyword(s):  
Transcription Regulation ◽  
Negative Feedback ◽  
Rate Constants ◽  
The Other ◽  
Type I ◽  
Type Ii ◽  
Biochemical Mechanism ◽  
Wide Range ◽  
Negative Feedbacks ◽  
Positive And Negative Feedbacks

Many biological systems contain both positive and negative feedbacks. These are often classified as resonators or integrators. Resonators respond preferentially to oscillating signals of a particular frequency. Integrators, on the other hand, accumulate a response to signals. Computational neuroscientists often refer to neurons showing integrator properties as type I neurons and those showing resonator properties as type II neurons. Guantes & Poyatos have shown that type I or type II behaviour can be seen in genetic clocks. They argue that when negative feedback occurs through transcription regulation and post-translationally, genetic clocks act as integrators and resonators, respectively. Here we show that either behaviour can be seen with either design and in a wide range of genetic clocks. This highlights the importance of parameters rather than biochemical mechanism in determining the system behaviour.

Signal transduction and TGF-β superfamily receptors

1996 ◽  
Vol 74 (3) ◽  
pp. 299-314 ◽  
Author(s):  
Steven M. Kolodziejczyk ◽  
Brian K. Hall
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Intracellular Signaling ◽  
Specific Cell ◽  
Type I ◽  
Type Ii ◽  
Type Iii ◽  
Wide Range ◽  
Transduction Mechanisms ◽  
Kinase Cascade

The TGF-β superfamily includes a large number of related growth and differentiation factors expressed in virtually all phyla. Superfamily members bind to specific cell surface receptors that activate signal transduction mechanisms to elicit their effects. Candidate receptors fall into two primary groups, termed type I and type II receptors. Both types are serine/threonine kinases. Upon activation by the appropriate ligand, type I and type II receptors physically interact to form hetero-oligomers and subsequently activate intracellular signaling cascades, ultimately regulating gene transcription and expression. In addition, TGF-β binds to a third receptor class, type III, a membrane-anchored proteoglycan lacking the kinase activity typical of signal transducing molecules. Type III receptors appear to regulate ligand availability to type I and type II receptors. Although a number of transduction mechanisms may be available to TGF-β superfamily members, evidence gathered through the use of specific kinase and G-protein inhibitors and through assays measuring activation and levels of signaling intermediates suggests that at least one signaling pathway interacts with Ras and Raf proteins via a G-protein intermediate. Raf begins the cytoplasmic kinase cascade that leads to gene regulation. The myriad responses regulated by TGF-β superfamily members makes the understanding of signal transduction mechanisms utilized by these proteins of great interest to a wide range of biological disciplines.Key words: TGF-β superfamily, serine/threonine kinase receptors, G-proteins, Ras, cytoplasmic kinase cascade.

scholarly journals Recent Developments in the Synthesis of Pyrido[1,2-a]benzimidazoles

Synthesis ◽  
2018 ◽  
Vol 50 (11) ◽  
pp. 2131-2149 ◽  
Author(s):  
Kamal Kapoor ◽  
Parthasarathi Das ◽  
Rajni Khajuria ◽  
Sk. Rasheed ◽  
Chhavi Khajuria
Keyword(s):  
Transition Metal ◽  
Medicinal Chemistry ◽  
Type I ◽  
Type Ii ◽  
Aromatic Rings ◽  
Metal Free ◽  
Wide Range ◽  
Recent Developments ◽  
Metal Catalyzed ◽  
Synthetic Approaches

Pyrido[1,2-a]benzimidazole is one of the most important azaheterocyclic compounds consisting of three fused aromatic rings. Molecules containing this core have displayed a wide range of applications in the field of medicinal chemistry. The synthesis of pyrido[1,2-a]benzimidazole and its derivatives has attracted organic chemists because of its tremendous utility in interdisciplinary branches of chemistry. In this context, this review discusses the main advances in the synthesis of pyrido[1,2-a]benzimidazoles via metal-mediated and metal-free reactions from 2000 to 2016.1 Introduction2 Synthetic Approaches to Pyrido[1,2-a]benzimidazoles2.1 Type I: Transition-Metal-Catalyzed Methods2.2 Type II: Metal-Free Approaches3 Conclusion

scholarly journals Molecular analysis of the T-cell acute lymphoblastic leukemia- associated t(1;7)(p34;q34) that fuses LCK and TCRB

Blood ◽  
1994 ◽  
Vol 84 (4) ◽  
pp. 1232-1236 ◽  
Author(s):  
RC Burnett ◽  
MJ Thirman ◽  
JD Rowley ◽  
MO Diaz
Keyword(s):  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Receptor Gene ◽  
Type I ◽  
Type Ii ◽  
Transcriptional Enhancer ◽  
Recognition Sequence ◽  
Chromosomal Breakage ◽  
Rnase Protection

Previously we had characterized the t(1;7)(p34;q34) translocation from HSB-2. This translocation fused the beta T-cell receptor gene (TCRB) constant region and transcriptional enhancer with the type I transcription unit of the LCK gene on the derivative 1 [der(1)] chromosome. The type II promoter was translocated to the der(7) chromosome. Regarding the mechanism of the t(1;7) in HSB-2, we identified an alternating purine-pyrimidine tract (G-T)17 at the 1p34/LCK breakpoint. Additionally, sequence analysis of both breakpoint junctions provided data that implicate the V(D)J recombinase in formation of the t(1;7). A heptamer-nonamer recognition sequence with a 12-bp spacer was found in the immediate vicinity of the 1p34/LCK breakpoint and, thus, chromosomal breakage at 1p34 may be explained as resulting from recombinase activity. Because phosphorylation of Tyr-505 in vivo regulates the tyrosine kinase activity of p56lck we amplified a region from LCK exon 12 that contains the codon for Tyr-505 and showed no mutation of this codon in HSB-2 DNA and, therefore, p56lck in HSB-2 is not activated by mutation of Tyr-505. We have analyzed LCK gene expression in HSB-2 and SUP-T12 cell lines. RNase protection analysis identified almost exclusively type I transcripts in HSB-2. An independent t(1;7) in SUP-T12 also resulted in the juxtaposition of LCK to TCRB. The breakpoint in SUP-T12 occurred 2 kb 5′ of the type II promoter, leaving an intact LCK gene on the der(1) chromosome. RNase protection analysis identified both type I and type II LCK transcripts in a 3:1 ratio in SUP-T12. Factors other than proximity to the TCRB enhancer must affect promoter utilization in this cell line.

scholarly journals Association Between Subtalar Articular Surface Typing and Flat Foot Deformity: Which Type is More Likely to Cause Flat Foot Deformity

2021 ◽  
Author(s):  
Lei Zhang ◽  
Xiaoyao Peng ◽  
Siyuan He ◽  
Xin Zhou ◽  
Gang Yi ◽  
...  
Keyword(s):  
Articular Surface ◽  
Type I ◽  
Type Ii ◽  
Foot Deformity ◽  
Imaging Data ◽  
Level Of Evidence ◽  
Flat Foot ◽  
Wide Range ◽  
Retrospective Comparative Study ◽  
Böhler’S Angle

Abstract Background Previous studies have shown a wide range of anatomical classifications of the subtalar joint (STJ) in the population and this is related to the different force line structures of the foot. Different subtalar articular surface morphology may affect the occurrence and development of flat foot deformity, and there are fewer studies in this area. The main objective of our study was to determine the association of different subtalar articular surface with the occurrence and severity of flat foot deformity. Methods We analyzed the imaging data of 289 cases of STJ. The articular surface area, Gissane's angle and Bohler's angle of subtalar articular surface of different types were counted. The occurrence and severity of flat foot deformity in different subtalar articular surface were judged by measuring the Meary angle of foot. Results We classified 289 cases of subtalar articular surface into five types according to the morphology. According to Meary angle, the flat foot deformity of Type Ⅰ and Type Ⅳ are significantly severer than Type Ⅱ (P < 0.05). Type II (7.65 ± 1.38 cm2) was significantly smaller than Type I (8.40 ± 1.79 cm2) in the total joint facet area(P < 0.05). Type III (9.15 ± 1.92 cm2) was smaller than Type I (8.40 ± 1.79 cm2), II(7.65 ± 1.38 cm2) and Ⅳ(7.81 ± 1.74 cm2 ) (P < 0.05).Type II (28.81 ± 7.44∘) was significantly smaller than Type I (30.80 ± 4.61 degrees), and IV (32.25 ± 5.02 degrees) in the Bohler’s angle (P < 0.05). Type II (128.49 ± 6.74 degrees) was smaller than Type I (131.58 ± 7.32 degrees), and IV (131.94 ± 5.80 degrees) in the Gissane’s angle (P < 0.05). Conclusions After being compared and analyzed the measurement of morphological parameters, joint facet area and fusion of subtalar articular surface were closely related to the severity of flat foot deformity and Type I and IV were more likely to develop severer flat foot deformity. Level of evidence: Level III, retrospective comparative study.

scholarly journals Biosynthesis of Polyketides in Streptomyces

2019 ◽  
Vol 7 (5) ◽  
pp. 124 ◽  
Author(s):  
Chandra Risdian ◽  
Tjandrawati Mozef ◽  
Joachim Wink
Keyword(s):  
Secondary Metabolites ◽  
Structure And Function ◽  
Polyketide Synthases ◽  
Type I ◽  
Type Ii ◽  
Filamentous Form ◽  
Gram Positive Bacteria ◽  
Wide Range ◽  
Different Types ◽  
And Function

Polyketides are a large group of secondary metabolites that have notable variety in their structure and function. Polyketides exhibit a wide range of bioactivities such as antibacterial, antifungal, anticancer, antiviral, immune-suppressing, anti-cholesterol, and anti-inflammatory activity. Naturally, they are found in bacteria, fungi, plants, protists, insects, mollusks, and sponges. Streptomyces is a genus of Gram-positive bacteria that has a filamentous form like fungi. This genus is best known as one of the polyketides producers. Some examples of polyketides produced by Streptomyces are rapamycin, oleandomycin, actinorhodin, daunorubicin, and caprazamycin. Biosynthesis of polyketides involves a group of enzyme activities called polyketide synthases (PKSs). There are three types of PKSs (type I, type II, and type III) in Streptomyces responsible for producing polyketides. This paper focuses on the biosynthesis of polyketides in Streptomyces with three structurally-different types of PKSs.

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