Mechanisms of Hormone Action

2011 ◽  
Author(s):  
Stephen R. Hammes ◽  
Carole R. Mendelson
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Nuclear Receptors ◽  
Plasma Membranes ◽  
Hormone Receptors ◽  
Membrane Receptors ◽  
Endocrine Disorders ◽  
Messenger Rnas ◽  
Dihydroxyvitamin D3 ◽  
Transduction Mechanisms

The capacity of a cell to respond to a particular hormone depends on the presence of cellular receptors specific for that hormone. After binding hormone, the receptor is biochemically and structurally altered, resulting in its activation; the activated receptor then mediates all of the actions of the hormone on the cell. The steroid and thyroid hormones as well as retinoids and 1,25-dihydroxyvitamin D3 diffuse freely through the lipophilic plasma membrane of the cell and interact with receptors that are primarily within the nucleus. On activation, the receptors alter the transcription of specific genes, resulting in changes in the levels of specific messenger RNAs (mRNAs), which are in turn translated into proteins. Hormones that are water soluble, such as the peptide and polypeptide hormones, catecholamines, and other neurotransmitters, as well as the relatively hydrophobic prostaglandins, interact with receptors in the plasma membrane. After hormone binding, the activated membrane receptors initiate signal transduction cascades that result in changes in enzyme activities and alterations in gene expression. In this chapter, the properties of various classes of receptors that are localized within the plasma membranes of target cells and the signal transduction mechanisms that mediate interactions with their ligands will first be addressed. This will be followed by consideration of the structural properties of the nuclear hormone receptors, the events that result in their activation, and the mechanisms whereby the activated nuclear receptors alter the expression of specific genes. Finally, a number of endocrine disorders that are caused by alterations in the number and/or function of plasma membranes and nuclear receptors will be reviewed. The function of a receptor is to recognize a particular hormone among all the molecules in the environment of the cell at a given time and, after binding the hormone, to transmit a signal that ultimately results in a biological response. Hormones are normally present in the circulation in extremely low concentrations, ranging from 10 –9 to 10 –11 M.

scholarly journals Luteinizing Hormone Receptors Translocate to Plasma Membrane Microdomains after Binding of Human Chorionic Gonadotropin

Endocrinology ◽  
2006 ◽  
Vol 147 (4) ◽  
pp. 1789-1795 ◽  
Author(s):  
Steven M. L. Smith ◽  
Ying Lei ◽  
Jingjing Liu ◽  
Mary E. Cahill ◽  
Guy M. Hagen ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Plasma Membranes ◽  
Hormone Receptors ◽  
Buoyant Density ◽  
Single Particle Tracking ◽  
Membrane Receptors ◽  
Membrane Microdomains ◽  
Low Density

Receptor-mediated signal transduction by G protein-coupled receptors can involve redistribution of plasma membrane receptors into membrane structures that are characterized by insolubility in Triton X-100 and low buoyant density in sucrose gradients. Here we describe the translocation of wild-type (wt) rat LH receptors (LHR-wt) from the bulk membrane into membrane microdomains (rafts) after the binding of human chorionic gonadotropin (hCG). In sucrose gradient ultracentrifugation of plasma membranes from cells stably expressing FLAG-tagged LHR-wt, receptors were located in high-density membrane fractions before binding of hormone and in low-density fractions after hCG treatment. Receptor translocation to low-density sucrose fractions did not occur when cells were pretreated with 1% methyl-β-cyclodextrin, which reduces membrane cholesterol and disrupts rafts. Single-particle tracking of individual FLAG-LHR-wt receptors showed that hCG-treated receptors become confined in small compartments with a diameter of 86 ± 36 nm, significantly smaller than 230 ± 79 nm diameter regions accessed by the untreated receptor. Receptors were no longer confined in these small compartments after disruption of rafts by methyl-β-cyclodextrin, a treatment that also decreased levels of cAMP in response to hCG. Finally, translocation of LHR into rafts required a functional hormone-receptor complex but did not occur after extensive receptor cross-linking that elevated cAMP levels. Thus, retention of LHR in rafts or small membrane compartments is a characteristic of functional, hormone-occupied LHR-wt. Although raft translocation was not essential for cAMP production, it may be necessary for optimizing hormone-mediated signaling.

scholarly journals Fluorescent, short-chain C6-NBD-sphingomyelin, but not C6-NBD-glucosylceramide, is subject to extensive degradation in the plasma membrane: implications for signal transduction related to cell differentiation

1995 ◽  
Vol 309 (3) ◽  
pp. 905-912 ◽  
Author(s):  
J W Kok ◽  
T Babia ◽  
K Klappe ◽  
D Hoekstra
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Cell Differentiation ◽  
Plasma Membranes ◽  
Cell Types ◽  
Short Chain ◽  
Synthetic Activity ◽  
Intact Cells ◽  
Ht29 Cells ◽  
Extensive Degradation

The involvement of the plasma membrane in the metabolism of the sphingolipids sphingomyelin (SM) and glucosylceramide (GlcCer) was studied, employing fluorescent short-chain analogues of these lipids, 6-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]hexanoylsphingosylphosphorylcholine (C6-NBD-SM), C6-NBD-GlcCer and their common biosynthetic precursor C6-NBD-ceramide (C6-NBD-Cer). Although these fluorescent short-chain analogues are metabolically active, some caution is to be taken in view of potential changes in biophysical/biochemical properties of the lipid compared with its natural counterpart. However, these short-chain analogues offer the advantage of studying the lipid metabolic enzymes in their natural environment, since detergent solubilization is not necessary for measuring their activity. These studies were carried out with several cell types, including two phenotypes (differing in state of differentiation) of HT29 cells. Degradation and biosynthesis of C6-NBD-SM and C6-NBD-GlcCer were determined in intact cells, in their isolated plasma membranes, and in plasma membranes isolated from rat liver tissue. C6-NBD-SM was found to be subject to extensive degradation in the plasma membrane, due to neutral sphingomyelinase (N-SMase) activity. The extent of C6-NBD-SM hydrolysis showed a general cell-type dependence and turned out to be dependent on the state of cell differentiation, as revealed for HT29 cells. In undifferentiated HT29 cells N-SMase activity was at least threefold higher than in its differentiated counterpart. In contrast, in all cell types studied, very little if any biosynthesis of C6-NBD-SM from the precursor C6-NBD-Cer occurred. Moreover, in the case of C6-NBD-GlcCer, neither hydrolytic nor synthetic activity was found to be associated with the plasma membrane. These results are discussed in the context of the involvement of the sphingolipids SM and GlcCer in signal transduction pathways in the plasma membrane.

scholarly journals Murine fetal liver macrophages bind developing erythroblasts by a divalent cation-dependent hemagglutinin.

1988 ◽  
Vol 106 (3) ◽  
pp. 649-656 ◽  
Author(s):  
L Morris ◽  
P R Crocker ◽  
S Gordon
Keyword(s):  
Plasma Membrane ◽  
Divalent Cation ◽  
Plasma Membranes ◽  
Fetal Liver ◽  
Divalent Cations ◽  
Membrane Receptors ◽  
Erythroid Cells ◽  
Mammalian Development ◽  
Trypsin Treatment ◽  
Plasma Membrane Receptors

During mammalian development the fetal liver plays an important role in hematopoiesis. Studies with the macrophage (M phi)-specific mAb F4/80 have revealed an extensive network of M phi plasma membranes interspersed between developing erythroid cells in fetal liver. To investigate the interactions between erythroid cells and stromal M phi, we isolated hematopoietic cell clusters from embryonic day-14 murine fetal liver by collagenase digestion and adherence. Clusters of erythroid cells adhered to glass mainly via M phi, 94% of which bound 19 +/- 11 erythroblasts (Eb) per cell. Bound Eb proliferated vigorously on the surface of fetal liver M phi, with little evidence of ingestion. The M phi could be stripped of their associated Eb and the clusters then reconstituted by incubation with Eb in the presence of divalent cations. The interaction required less Ca++ than Mg++, 100 vs. 250 microM for half-maximal binding, and was mediated by a trypsin-sensitive hemagglutinin on the M phi surface. After trypsin treatment fetal liver M phi recovered the ability to bind Eb and this process could be selectively inhibited by cycloheximide. Inhibition tests showed that the Eb receptor differs from known M phi plasma membrane receptors and fetal liver M phi did not bind sheep erythrocytes, a ligand for a distinct M phi hemagglutinin. We propose that fetal liver M phi interact with developing erythroid cells by a novel nonphagocytic surface hemagglutinin which is specific for a ligand found on Eb and not on mature red cells.

Progesterone interaction with sperm plasma membrane, calcium influx and induction of the acrosome reaction

1999 ◽  
Vol 7 (2) ◽  
pp. 81-93 ◽  
Author(s):  
Christopher Bray ◽  
Jackson CK Brown ◽  
Steve Publicover ◽  
Christopher LR Barratt
Keyword(s):  
Plasma Membrane ◽  
Steroid Hormones ◽  
Nuclear Receptors ◽  
Acrosome Reaction ◽  
Calcium Influx ◽  
Membrane Receptors ◽  
Sperm Plasma Membrane ◽  
The Subject ◽  
Genomic Effects ◽  
Intense Research

In contrast to the classic action of steroid hormones through cytoplasmic/nuclear receptors, there is an accumulating body of data which strongly suggests that they have a direct effect on cells mediated through putative membrane receptors, a so-called non-genomic action. Although such non-genomic effects were discovered 50 years ago it is only in the last 15 years that the subject has become an area of intense research.

scholarly journals Integrin-associated protein: a 50-kD plasma membrane antigen physically and functionally associated with integrins.

1990 ◽  
Vol 111 (6) ◽  
pp. 2785-2794 ◽  
Author(s):  
E Brown ◽  
L Hooper ◽  
T Ho ◽  
H Gresham
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Synthetic Peptides ◽  
Plasma Membranes ◽  
Protein A ◽  
Hematopoietic Cells ◽  
Cell Types ◽  
Cell Biol ◽  
Leukocyte Response ◽  
Stimulation Of

Phagocytosis by monocytes or neutrophils can be enhanced by interaction with several proteins or synthetic peptides containing the Arg-Gly-Asp sequence. Recently we showed that an mAb, B6H12, specifically inhibited this enhancement of neutrophil phagocytosis by inhibiting Arg-Gly-Asp binding to the leukocyte response integrin (Gresham, H. D., J. L. Goodwin, P. M. Allen, D. C. Anderson, and E. J. Brown. 1989. J. Cell Biol. 108:1935-1943). Now, we have purified the antigen recognized by B6H12 to homogeneity. Surprisingly, it is a 50-kD molecule that is expressed on the plasma membranes of all hematopoietic cells, including erythrocytes, which express no known integrins. On platelets and placenta, but not on erythrocytes, this protein is associated with an integrin that can be recognized by an anti-beta 3 antibody. In addition, both the anti-beta 3 and several mAbs recognizing the 50-kD protein inhibit Arg-Gly-Asp stimulation of phagocytosis. These data demonstrate an association between integrins and the 50-kD protein on several cell types. For this reason, we call it Integrin-associated Protein (IAP). We hypothesize that IAP may play a role in signal transduction for enhanced phagocytosis by Arg-Gly-Asp ligands.

Signaling Receptome: A Genomic and Evolutionary Perspective of Plasma Membrane Receptors Involved in Signal Transduction

2003 ◽  
Vol 2003 (187) ◽  
pp. re9-re9 ◽  
Author(s):  
I. Ben-Shlomo ◽  
S. Yu Hsu ◽  
R. Rauch ◽  
H. W. Kowalski ◽  
A. J. W. Hsueh
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Membrane Receptors ◽  
Evolutionary Perspective ◽  
Plasma Membrane Receptors

scholarly journals Renal plasma membrane receptors for certain modified serum albumins Evidence for participation of a heparin receptor

1986 ◽  
Vol 239 (3) ◽  
pp. 537-543 ◽  
Author(s):  
P N Ranganathan ◽  
J L Mego
Keyword(s):  
Plasma Membrane ◽  
Plasma Membranes ◽  
Dissociation Constants ◽  
Chondroitin Sulphate ◽  
Specific Binding ◽  
Membrane Receptors ◽  
Heparin Binding ◽  
Serum Albumins ◽  
Plasma Membrane Receptors ◽  
Renal Plasma Membranes

Binding of formaldehyde-treated (f-alb), reduced-carboxymethylated (ac-alb) or reduced-acetamidated (am-alb) bovine serum albumins to purified rat renal plasma membranes was studied. Radioiodinated f-alb or ac-alb bound to kidney membranes while am-alb neither bound significantly nor competed with f-alb binding to kidney membranes. The binding was specific, saturable and heat- and proteinase-sensitive. Competition studies showed that f-alb and ac-alb sites may be the same on these membranes. To determine the role played by charge in binding, competition experiments with polyanions were performed. Polyanions such as nucleic acid or glycosaminoglycans were effective competitors of f-alb binding to cell membranes. Heparin was especially inhibitory, being several-fold more so than chondroitin sulphate. Completely reduced and carboxymethylated albumin was a better competitor than its partially modified counterpart. Furthermore, f-alb was a significant competitor of [35S]heparin binding to kidney membranes. Also, partially purified heparin receptor demonstrated specific binding of 125I-f-alb. These data suggest that a heparin receptor is responsible for binding and internalization of intravenously injected f-alb. A Scatchard plot revealed two classes of receptors with dissociation constants of 3.2 × 10(-6) M and 4.7 × 10(-5) M.

scholarly journals Defect in signal transduction at the level of the plasma membrane accounts for inability of insulin to activate pyruvate dehydrogenase in white adipocytes of lactating rats

1988 ◽  
Vol 252 (3) ◽  
pp. 667-672 ◽  
Author(s):  
E Kilgour ◽  
R G Vernon
Keyword(s):  
Signal Transduction ◽  
Adipose Tissue ◽  
Plasma Membrane ◽  
Pyruvate Dehydrogenase ◽  
Plasma Membranes ◽  
Insulin Binding ◽  
White Adipocytes ◽  
Isolated Adipocytes ◽  
No Activation

1. The mechanism responsible for the failure of insulin to activate pyruvate dehydrogenase (PDH) in white adipose tissue in vivo during lactation was investigated. 2. Insulin failed to increase PDH in isolated adipocytes from lactating rats. 3. Insulin binding to plasma membranes from adipocytes was unchanged by lactation. 4. Incubation of plasma membranes plus permeabilized mitochondria from adipocytes in the presence of insulin resulted in activation of PDH when the plasma membranes were obtained from virgin rats, whereas no activation was observed when plasma membranes from lactating rats were used. 5. The results show that the failure of insulin to activate PDH in adipose tissue from lactating rats is due to a failure of the signal-transduction system in the plasma membrane at steps subsequent to insulin binding to the insulin receptor.

Blue Light-Induced Phosphorylation of a Plasma Membrane Protein in Pea: a Step in the Signal Transduction Chain for Phototropism

1993 ◽  
Vol 20 (5) ◽  
pp. 393 ◽  
Author(s):  
KMF Warpeha ◽  
WR Briggs
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Blue Light ◽  
Plasma Membranes ◽  
Signal Transduction Pathway ◽  
Light Signal ◽  
Denatured State ◽  
Ionic Detergent ◽  
Induced Signal

A 117 kDa polypeptide associated with the plasma membrane isolated from the growing zones of etiolated pea epicotyls is phosphorylated upon a brief exposure to blue light. The literature pertaining to this photosensitive system to date is briefly summarised prior to a short experimental section. In the experimental work the polypeptide has been studied in its non-denatured and denatured state in order to investigate its possible role in blue light-induced signal transduction. The polypeptide has a molecular weight near 117 kDa. Under non-denaturing conditions, following solubilisation in non-ionic detergent, and after electrophoresis, a complex migrating at approximately '335 kDa' still retains the ability to perceive the blue light signal and undergo phosphorylation. This complex is resolved into a phosphorylated protein of approximate molecular mass of 117 kDa by second dimensional analysis on denaturing polyacrylamide gels. It is not at present possible to determine whether this protein is the only one involved or whether two or more different proteins are required for the light-inducible phosphorylation. This reaction has been established elsewhere by genetic and physiological criteria to be an early step in the signal transduction pathway for phototropism. Two other reactions that are inducible in vitro in isolated plasma membranes from etiolated seedings - activation of GTPase activity and reduction of a b-type cytochrome-are almost certainly independent pathways unrelated to the phosphorylation reaction or to each other. Neither has as yet been associated definitively with a known physiological response.

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