Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Addition of the cyclic AMP phosphodiesterase inhibitors theophylline (10- minus 2 M) or papaverine (10- minus 4 M) leads to a complete inhibition of lactose synthesis in incubated guinea pig mammary gland slices. Addition of 10- minus 5 M cyclic AMP or dibutyryl cyclic AMP results in 1 30-40% inhibition of the synthesis, which effect is not increased by applying higher concentrations of these compounds. A 30-40% inhibition can also be obtained with epinephrine (5 - 10- minus 5 M), or isoproterenol (10- minus 4 M), but the polypeptide hormones glucagon (10- minus 7 M), insulin (1 munit/ml) and relaxin (10 mug/ml) do not significantly affect lactose synthesis. Cytochalasin B (5 mug/ml) inhibits lactose production by 58and colchicine (10- minus 5 M) by 25%. These experiments suggest that an increase in the intracellular level of cyclic AMP either through its addition, through hormonal stimulation of its synthesis, or through inhibition of its intracellular breakdown, leads to an inhibition of lactose production in lactating mammary gland. This effect of cyclic AMP is similar to that of progesterone, which is known to inhibit lactation in vivo and the withdrawal of which at parturition has been postulated to initiate lactogenesis.
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PMID:Inhibition by cyclic AMP of lactose production in lactating guinea pig mammary gland slices. 16 55

Relaxin is an ovarian peptide that is released just prior to parturition to effect changes in the tissues of the birth canal that aid in the delivery of the fetus. Structural studies established that the two constituent polypeptide chains, composed of 22 and 30 amino acids, are joined by two interchain disulfide bonds with an additional third intrachain bridge. As well as the identical pattern of disulfide bonds, relaxin shows an overall 25% identity with insulin. Furthermore, the sequence of relaxin can be incorporated into the known three-dimensional structure of insulin without significant distortion of the main polypeptide chain backbone. The discovery of the insulin-relatedness of relaxin brings to three the number of growth factors that share a common structural gene precursor with insulin. Nerve growth factor and insulin-like growth factor have already been so identified. Inclusion in this hormone family suggests that the mechanism of action may involve internalization as well as complexation with cell surface receptors of target cells.
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PMID:Relaxin: an insulin-related growth factor. 39 38

In several mammalian species, the polypeptide hormone, relaxin, prepares the reproductive tract for parturition. In rats, relaxin is secreted by the ovaries during the last week of a 22-day pregnancy. There is a failure of parturition in ovariectomized pregnant rats. In this study relaxin was injected into rats in the periimplantation period . The effects of relaxin on the response of the pregnant rat to a subabortifacient dose of prostaglandin F2-alpha (PGF2-alpha) was tested. Swine ovarian relaxin preparations were injected sc as a single dose on days 3,4, or 5 of pregnancy or as multiple doses on Days 3-5 or 4 and 5. Progesterone was injected sc on Days 3-6 or 2-9 of pregnancy. Dexamethasone was given orally on Days 4-6. Indomethacin was given by gavage on Days 3-6. PGF2-alpha was injected as a single dose on Day 5, alone or in combination with relaxin. Rats were killed on Day 10 and the uterine contents observed. Injections of .5 mg (but not of .1 mg) relaxin daily on Days 3-5 of pregnancy induced resorption of a large number of fetuses. Single doses of 1 mg relaxin given on Day 4 or 5, but not when given on Day 3, terminated pregnancy in rats. Progesterone, but not indomethacin, given on Days 3-5 prevented termination of pregnancy by relaxin given on Day 5. Resorption of litters induced by .5 mg doses of relaxin given on Days 4 or 5 prevented by daily injections of progesterone given from Days 2 to 9. Injections of 10 or 30 mcg of dexamethasone on Days 4, 5, and 6 partially or completely reversed the adverse effects of relaxin on litter survival. A single injection of 1 mg of PGF2-alpha on Day 5 failed to affect the pregnancy, but when given following a .1 mg dose of relaxin given on Days 3, 4, and 5 nearly complete resorption of litters resulted. These 2 compounds are therefore thought to act synergistically. Serum progesterone levels 24 hours after a single injection of 1 mg of purified relaxin were the same as controls. It is suggested that relaxin may antagonize the progesterone "block" to coordinated uterine contractions.
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PMID:Effects of relaxin on early pregnancy in rats. 94 92

Squamous cell differentiation in tracheobronchial epithelial cells is accompanied by many biochemical and molecular changes. One of the molecular changes in rabbit tracheal epithelial (RbTE) cells is the differential expression of a squamous cell-specific mRNA encoded by the complementary DNA SQ10. In this study, we sequenced SQ10 complementary DNA and showed that this gene encodes a preprorelaxin-like protein. The DNA sequence of the coding region of SQ10 has 68% identity with the human preprorelaxin mRNA, whereas the deduced amino acid sequence exhibits 46% identity with human preprorelaxin. An antiserum (pepIV-Ab) was raised against a synthetic 22-amino acid oligopeptide of the protein encoded by SQ10. Immunoblot analysis of cellular extracts of squamous-differentiated cells showed that this antiserum reacted with proteins of 22 and 20 kilodaltons, possibly constituting prepro- and proforms of this protein. These proteins were undetectable in undifferentiated RbTE cells. In agreement with these observations, PepIV-Ab specifically stained the cytosol of squamous-differentiated RbTE cells but failed to stain undifferentiated cells. PepIV-Ab recognized a 20 and 16 kilodalton polypeptide in medium conditioned by squamous-differentiated RbTE cells, indicating that the prorelaxin-like protein is secreted. The amino acid sequences of three peptides that were obtained after tryptic digestion of the secreted 16 kilodalton protein were identical to sequences encoded by SQ10. Retinoids which have been shown to inhibit squamous differentiation suppressed the induction of SQ10 protein as well as mRNA in a concentration-dependent manner. The concentration at which retinoic acid caused a 50% inhibition of SQ10 mRNA levels was approximately 5 nM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of a preprorelaxin-like gene during squamous differentiation of rabbit tracheobronchial epithelial cells and its suppression by retinoic acid. 133 18

Relaxin is a polypeptide hormone involved in remodeling of the birth canal during parturition. It is synthesized as a preprohormone precursor, which undergoes specific processing to form the mature two-chain disulfide-linked active species that is secreted by the cell. A major part of this processing requires endoproteolytic cleavage at specific pairs of basic amino acid residues, an event necessary for the maturation of a variety of important biologically active proteins, such as insulin and nerve growth factor. Human type 2 preprorelaxin was coexpressed in human kidney 293 cells with the candidate prohormone convertase-processing enzymes mPC1 or mPC2, both cloned from the mouse pituitary tumor AtT-20 cell line, or with the yeast kex2 alpha-mating factor-converting enzyme from Saccharomyces cerevisiae. Prorelaxin expressed alone in 293 cells was secreted into the culture medium unprocessed. Transient coexpression with mPC1 or kex2, but not with mPC2, resulted in the secretion of a low mol wt species with an electrophoretic mobility very similar, if not identical, to that of authentic mature relaxin purified from human placenta. This species was precipitable by monoclonal antibodies specific for relaxin and had a retention time on reverse phase HPLC comparable to that of relaxin. Its analysis by both electrospray and fast atom bombardment mass spectrometry generated mass data that were consistent only with mature relaxin. The basic residues required for mPC1-dependent cleavage of prorelaxin are defined by site-directed mutagenesis.
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PMID:Prohormone convertase-1 will process prorelaxin, a member of the insulin family of hormones. 143 88

Relaxin is a 56-amino acid polypeptide that produces relaxation of the pubic ligament. Ten young male pigs were implanted with tissue expanders and osmotic pumps. The pumps in five animals contained recombinant human relaxin to produce a serum relaxin level of 1 ng/mL. The other five pumps contained saline. Repeated measurements of the pressure-volume expansion curves showed a significant decrease in the pressure needed to fill the expanders in the relaxin group compared with the control group. Dermal thickness in the control group and epidermal thickness in both control and experimental groups were increased on histomorphometric measurement. No adverse effects were seen in the relaxin group. Relaxin facilitates tissue expansion in pigs without affecting dermal thickness.
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PMID:The effect of relaxin on tissue expansion. 154 Mar 45

Relaxin is a member of the insulin family of polypeptide hormones and exerts its best understood actions in the mammalian reproductive system. Using a biologically active 32P-labeled human relaxin, we have previously shown by in vitro autoradiography specific relaxin binding sites in rat uterus, cervix, and brain tissues. Using the same approach, we describe here a detailed localization of human relaxin binding sites in the rat brain. Displaceable relaxin binding sites are distributed in discrete regions of the olfactory system, neocortex, hypothalamus, hippocampus, thalamus, amygdala, midbrain, and medulla of the male and female rat brain. Characterization of the relaxin binding sites in the subfornical organ and neocortex reveals a single class of high-affinity sites (Kd = 1.4 nM) in both regions. The binding of relaxin to two of the circumventricular organs (subfornical organ and organum vasculosum of the lamina terminalis) and the neurosecretory magnocellular hypothalamic nuclei (i.e., paraventricular and supraoptic nuclei) provides the anatomical and biochemical basis for emerging physiological evidence suggesting a central role for relaxin in the control of blood pressure and hormone release. We conclude that specific, high-affinity relaxin binding sites are present in discrete regions of the rat brain and that the distribution of some of these sites may be consistent with a role for relaxin in control of vascular volume and blood pressure.
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PMID:Autoradiographic localization of relaxin binding sites in rat brain. 165 Apr 66

The X-ray crystal structure of relaxin at 1.5 A resolution is reported for the physiologically active form of the human hormone. Relaxin is a small, two-chain polypeptide that is a member of the protein hormone family that also includes insulin and the insulin-like growth factors IGF-I and IGF-II. These hormones have biologically diverse activities but are structurally similar, sharing a distinctive pattern of cysteine and glycine residues. The predicted structural homology of relaxin to insulin is confirmed by this structural analysis; however, there are significant differences in the terminal regions of the b-chain. Although relaxin, like insulin, crystallizes as a dimer, the orientation of the molecules in the respective dimers is completely different. The region of the relaxin molecule proposed to be involved in receptor binding is part of the dimer interface, suggesting that some of the other residues contained in the dimer contact surface might be receptor binding determinants as well. The proposed receptor binding determinants for insulin likewise include residues at its dimer interface. However, because the dimer contacts of relaxin and insulin are quite different, it appears that these two structurally related hormones have evolved somewhat dissimilar mechanisms for receptor binding.
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PMID:X-ray structure of human relaxin at 1.5 A. Comparison to insulin and implications for receptor binding determinants. 165 49

Since peptide mapping with proteolytic enzymes such as trypsin and Staphylococcus aureus V8 protease is a powerful tool for the characterization of proteins, investigators should be cognizant of possible artifacts due to the technique itself. This article describes the identification of minor peaks found in the maps of recombinant human relaxin and insulin-like growth factor I as transpeptidation products. Both proteins have some homology to insulin with relaxin being composed of two chains designated A and B, while insulin-like growth factor I is composed of a single polypeptide chain. Digestion of relaxin with trypsin at pH 7.2 yields two peptides, T2,3(A10-18) and T7(B10-13), linked together by a disulfide bond. An unexpected component at a 10% level was identified to be the T2-T7 peptide pair where T3(ArgA18) has formed a peptide bond with the amino-terminal LeuB10 of the T7 peptide. It was also observed that the digestion of insulin-like growth factor I with V8 protease normally yields two peptides V4(13-20) and V9(59-70) linked by a disulfide bridge. A minor peak at a 1 to 2% level was identified to be a single polypeptide resulting from the formation of a peptide bond between the amino-terminal Met59 of V9 and the carboxyl-terminal Asp20 of V4, with the disulfide bond intact. These transpeptidation products were isolated by reversed-phase HPLC and identified using amino-terminal sequence and mass spectrometric analyses.
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PMID:Transpeptidation during the analytical proteolysis of proteins. 188 34

The human placenta and decidua are intrauterine production sites for a range of polypeptide hormones. Relaxin is one of these hormones, its production having been demonstrated by immunocytochemistry and Northern analysis. There are two relaxin genes in the human genome, termed H1 and H2; only the latter is expressed in cyclic and pregnant corpus luteum. However, it has recently been shown that both genes are expressed in the decidua and placenta. It is not known whether both are translated. These hormone(s) may act in a paracrine fashion and be partly responsible for the control of enzymes and inhibitors involved in collagen remodelling in the fetal membranes in the last weeks of pregnancy. An autocrine role of decidual relaxin and a possible decidual-cell/macrophage/extracellular-matrix interaction is described; this may act as a unit in the elaboration of a range of hormones.
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PMID:Human decidual and placental relaxins. 195 26


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