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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction between the plant lectin concanavalin A (Con A) and hepatic receptors for human growth hormone (GH) has been studied in particulate and soluble microsomal membrane preparations from rabbit and rat liver. Con A shows a dose-dependent, partial (30%) inhibition of 125I-human GH binding which is reversed by the Con A competitor, alpha-methyl mannoside. The Con A effect is dependent on the receptor concentration. The inhibition by Con A in rabbit liver is a reflection of a decreased number of available binding sites--there is no effect on binding affinity. It would appear that Con A binds directly to the GH-binding protein and not to an adjacent membrane glycoprotein. The GH receptor may consist of more than one molecular species, differing only in the carbohydrate type or content.
Mol Cell Endocrinol 1979 Nov
PMID:Interaction between the hepatic growth hormone receptor and concanavalin A. 22 48

In this study we investigated the involvement of several different pituitary hormones on rat prostate development. 22-day-old Wistar rats, hypophysectomized (hypox) at 19 days of age were supplemented with highly purified human prolactin (hPRL), human luteinizing hormone (hLH), porcine follicle-stimulating hormone (pFSH), and bovine growth hormone (bGH) or with saline. Quantitative analysis of RNAs shows that treatment with either PRL or GH increases significantly steady-state mRNAs levels of the following genes in the prostate: androgen receptor (AR) (respectively 3.5- and 4.8-fold above hypox controls), IGF-I (5- and 2.7-fold), and IGF-I receptor (2.9- and 2.3-fold). LH and FSH, by contrast, have negative effects on these parameters. To test whether the enhancing effect of PRL and GH on AR-mRNA abundance was followed by increased content in the protein itself, binding assays were performed with the androgen agonist [3H]R1881 (131 and 153 fmol/mg protein while hypox controls contained 110 fmol/mg protein). In addition to the well-documented presence of prolactin receptors in prostatic tissues, we have further demonstrated, by means of nuclease S1 protection assays plus dot- and Northern-blot analyses, that a GH receptor mRNA is produced in the immature rat prostate. Moreover, we observed not only strong lactogenic but also purely somatogenic binding to be occurring in the immature prostates. Finally, we have studied IGF-I mRNA content in separated epithelial/stromal cell fractions and have concluded that IGF-I expression is principally located in the prostatic stroma. Taken together, these results suggest that PRL and GH are involved in regulating AR synthesis, at least partially by direct action on the organ. In this context IGF-I appears as a paracrine factor playing a role in epithelium/stroma interactions during prostatic development.
Mol Cell Endocrinol 1992 Oct
PMID:Growth hormone and prolactin stimulate androgen receptor, insulin-like growth factor-I (IGF-I) and IGF-I receptor levels in the prostate of immature rats. 136 Sep 28

We have recently cloned a cDNA encoding a mutant form of PRL receptor (PRL-R) from Nb2 cells, a PRL-dependent T lymphocyte-derived cell line. This cDNA is identical to the long form of the rat PRL-R, except for a deletion of 594 base pairs in the cytoplasmic domain, resulting in a mature receptor protein of 393 amino acids. Although a segment containing three cytoplasmic regions of moderate to high amino acid sequence identity with members of the PRL/GH receptor family is missing in this receptor form, the region of highest (70%) identity is retained. In the following studies, a homologous functional assay was developed to test the activity of three forms of receptor with respect to their ability to transmit a lactogenic signal. In this system, CHO cells were transiently transfected with a construct containing 2300 base pairs of the 5'-flanking sequence of the rat beta-casein gene fused to the chloramphenicol acetyltransferase (CAT) gene and an expression vector containing the various forms of rat PRL-R cDNA. The transfected cells were grown in serum-free medium in the absence or presence of PRL. In cells transfected with the long form of the PRL-R and beta-casein/CAT construct, a 7.2- +/- 0.9-fold induction (n = 3) of CAT activity was seen when cells were cultured in the presence of 400 ng/ml PRL and 1 micrograms/ml hydrocortisone. This level of stimulation was similar to that observed for the ovine beta-lactoglobulin/CAT construct in which a 5.7- +/- 1.2-fold (n = 3) effect was found.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1992 Aug
PMID:The Nb2 form of prolactin receptor is able to activate a milk protein gene promoter. 140 2

Residues within the first disulphide loop of the GH receptor are highly conserved, and the two cysteines forming this motif are conserved across many cytokine receptors. We have used site-directed mutagenesis and the polymerase chain reaction with splicing by overlap extension to show that these residues are essential for binding of bovine (b)GH and human (h)GH to the rabbit GH receptor. When all residues within this loop were replaced with an equivalent polyalanine sequence, hormone binding was abolished. Conversion of Arg 39 within the loop to aspartate (R39D) decreased affinity for bGH by up to 20-fold. Conversion of Glu 42 to lysine (E42K) also resulted in a fivefold loss of affinity for bGH. However, charge reversals at Lys 37, Glu 44 and the conversion of Leu 43 to an arginine (as in the human receptor) were without a major effect on bGH binding. The lack of effect of the L43R mutation on bGH affinity, despite a significant (threefold) decrease in hGH affinity, argues against a role for Arg 43 as a residue conferring primate GH-binding specificity on the human receptor. Examination of the affinities of poly Ala, R39D and E42K mutants for a variety of hormone-binding-site directed and other monoclonal antibodies (MAbs) to the GH receptor revealed that these mutations were without a major effect on tertiary structure. It is of interest that the epitopes for the hormone-binding inhibitory MAbs 263 and 7 are located within this first loop, since the poly Ala mutation abolished the binding of both MAbs, and the R39D mutation abolished binding of MAb 7.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Endocrinol 1992 Dec
PMID:The first disulphide loop of the rabbit growth hormone receptor is required for binding to the hormone. 147 8

Structural heterogeneity has been demonstrated for growth hormone (GH) receptors from a number of species, and both high and low affinity art receptors have been characterised by ligand binding studies. In the present study, we have transfected Chinese hamster ovary (CHO-K1) cells with a cDNA clone encoding a full-length transmembrane ovine (o) GH receptor, under the regulatory control of the human metallothionein IIA promoter. A stably transfected cell line was established (GHR9.5) which expresses on the cell surface a single class of receptor which binds 220,000 [125I]oGH molecules at high affinity (Kd = 0.30 nM) which is comparable to the affinity established for endogenous oGH receptors in postnatal sheep liver microsomes (Kd = 0.27 nM, Freemark et al. (1987) Endocrinology 120, 1865-1872). The expressed receptor also binds ovine placental lactogen (oPL, 205,000 binding sites per cell) with high affinity (Kd = 0.76 nM). The presence of two species of oGH receptor was detected in GHR9.5 cells using affinity cross-linking analysis (M(r) 148,000 and M(r) 73,000) and given that the oGH receptor cDNA codes for a non-glycosylated receptor of M(r) 69,914, it is likely that these cross-linked species correspond to homodimeric and monomeric forms of the oGH receptor, each binding to a single molecule of GH. Parallel cross-linking studies with sheep liver microsomes also demonstrated two oGH receptor species (M(r) 133,000 and M(r) 58,000), the difference in relative molecular weights between the transfected and endogenous receptors presumably resulting from tissue-specific post-translational modifications. In the presence of oGH, the GHR9.5 cells respond by increasing total cellular protein synthesis by 27% relative to non-GH-exposed GHR9.5 cells, indicating the functionality of the expressed receptor. We also demonstrate unequivocally that oPL, through a specific interaction with the transfected oGH receptor, is able to mediate a similar cellular response (38% protein synthesis induction). Responsiveness to oGH and oPL in the GHR9.5 cells is dependent on serum starvation prior to oGH exposure and occurs only with prolonged exposure (greater than 2 h) to oGH. This cellular stimulation occurs independently of c-fos transcription which has previously been shown to be one of the earliest events associated with GH action in tissues expressing endogenous GH receptors (Doglio et al. (1989) Proc. Natl. Acad. Sci. USA 86, 1148-1152; Slootweg et al. (1990) J. Mol. Endocrinol. 4, 265-274).
Mol Cell Endocrinol 1992 Jul
PMID:Functional expression of an ovine growth hormone receptor in transfected Chinese hamster ovary cells. 151 79

Little is known of the regulation of gene expression for the family of growth hormone (GH) and prolactin (PRL) receptors (PRL-R). Furthermore, the relationship between expression of the GH receptor (GHR) and its soluble truncated form (GH-binding protein, GHBP) is unclear. The actions of both GH and PRL are developmentally regulated and several studies have examined the ontogeny of these receptors by classical hormone-binding techniques. In the current study we have examined the expression of GHR/GHBP and PRL-R mRNA in the male rat over a broad developmental range--fetal through to 110 days of age. The GHR mRNA (4.5 kb) was barely detectable in fetal and early (less than 20 days) postnatal livers, but was followed by a gradual increase up to 40 days of age by which time adult plateau levels were reached. In contrast, hepatic GHBP mRNA (1.2 kb) was clearly identifiable in the fetus and subsequently followed a similar pattern to the 4.5 kb GHR mRNA although there was a somewhat earlier rise. Hepatic membrane binding studies using 125I-bovine GH as ligand revealed no measurable binding activity at less than 20 days of age. Binding remained low thereafter. In contrast, the serum GHBP binding activity was detectable at 10 days of age and rose to adult levels by 50 days of age. These results indicate that mRNA species for GHR, GHBP, PRL-R and insulin-like growth factor I (IGF-I) are all developmentally regulated with the pattern for IGF-I correlating more closely with that of GHBP than GHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 Feb
PMID:Ontogeny of messenger RNA for the rat growth hormone receptor and serum binding protein. 154 8

Four members of the GH gene family, human (h) GH-V, human chorionic somatomammotropin-A (hCS-A), hCS-B, and hCS-L, are expressed in the human placenta. In attempting to define the role of these hormones in placental development, we have structurally characterized the human placental GH receptor (GHR) mRNA. Human GHR cDNAs were cloned from a human placental cDNA library. Clone pGHR-P1 encompasses the entire hGHR-coding region and is identical to the previously reported liver hGHR cDNA, except for a precise deletion of the sequences corresponding to exon 3. This mRNA with an exon 3 deletion is the sole form of the hGHR mRNAs in the placental villi. A reverse transcription/polymerase chain reaction assay was used to further characterize GHR mRNA expression. Human GHR mRNA was detected in all placental tissues as well as in a wide spectrum of other tissues and cell lines. The distribution of the exon 3-retaining and exon 3-excluding isoforms of the hGHR mRNA shows distinct tissue specificity. Some tissues and cell lines contain only one of the two forms, and some contain a mixed population. Since exon 3 encodes a segment in the extracellular domain of the receptor, its alternative inclusion or exclusion may mediate critical alterations in hormone binding and physiological function.
Mol Endocrinol 1992 Feb
PMID:Expression of a human growth hormone (hGH) receptor isoform is predicted by tissue-specific alternative splicing of exon 3 of the hGH receptor gene transcript. 156 71

This study was designed to investigate whether growth hormone (GH) influences the expression of its own receptor in chondrocytes. To investigate this possibility GH-receptor mRNA was measured in cultured rat epiphyseal chondrocytes in the absence or presence of GH under various experimental conditions. Chondrocytes were isolated enzymatically from epiphyseal growth plates of the proximal tibia of 20-day-old male rats and cultured in monolayer in Ham's F-12 medium supplemented with 10% calf serum and 1% of a serum substitute. The cells were seeded at various densities (100,000-1,000,000 cells per flask) and cultured for 14 days. Subsequently, the calf serum-containing medium and the cells cultured for various periods of time (0-24 h) before total nucleic acid preparation. GH-receptor mRNA was measured with a solution hybridization technique using [35S]UTP-labeled RNA growth hormone receptor cloned from rat liver cDNA. Human GH (hGH; 50 ng/ml) increased GH-receptor mRNA after 3 h and maximal levels were seen 12 h after GH addition. This effect of hGH was time and dose dependent with a significant effect of hGH at a concentration of 0.5 ng/ml and a maximal effect at 50 ng/ml. The hGH-stimulated increase of GH-receptor mRNA was completely blocked by actinomycin-C1 (1.0-0.1 micrograms/ml), while cycloheximide (10 micrograms/ml) only slightly counteracted the hGH effect. Rat and human GH were equally potent, and ovine prolactin was effective at 500 ng/ml but not 5 and 50 ng/ml. A high dose of insulin-like growth factor-I (IGF-I; 1 microgram/ml) caused a small stimulatory effect and addition of 10% calf serum caused a marked increase in GH-receptor mRNA. The level of GH receptor mRNA after 14 days of culture was inversely proportional to the cell density at the start of culture. These results show that GH specifically regulates mRNA levels for its own receptor in rat epiphyseal chondrocytes by interacting with somatogenic binding sites. These findings also suggest a transcription-dependent regulatory system between the GH-receptor and the GH-receptor gene.
Mol Cell Endocrinol 1990 May 07
PMID:Growth hormone regulation of the growth hormone receptor mRNA in cultured rat epiphyseal chondrocytes. 169 5

In this study a solution hybridization assay was evaluated for its application to the measurement of levels of specific mRNAs. The evaluation included parameters such as incubation time, hybridization stringency and probe concentration/structure. Both short (50 bases derived from synthetic oligonucleotides) and long (125-147 bases) RNA probes, derived from cloned sequences, could be used to obtain quantitative information on specific mRNA species. The solution hybridization assay was used to compare the levels of insulin-like growth factor-I (IGF-I) and IGF-II mRNAs in various rat and human tissues. In the rat the liver was the main source of IGF-I mRNA (approximately 400 molecules/cell), but significant levels were also found in extrahepatic tissues such as fat and muscle (3-50 molecules/cell). Human liver contained approximately 100-fold less IGF-I mRNA than rat liver. Human fat, muscle and placenta contained levels of IGF-I mRNA (2-8 molecules/cell) similar to those in the liver. Levels of IGF-II mRNA in rat and human tissues were similar, in that the expression was greatest in the placenta (approximately 200 molecules/cell). Species differences were evident, however, since human liver and fat contained significant amounts of IGF-II mRNA (15-20 molecules/cell), while the rat counterparts had almost undetectable levels. Young and old rats were used to examine the influence of age on the expression of IGF-I and GH receptor mRNAs in the liver. Levels of both IGF-I mRNA and GH receptor mRNA were found to decrease with age (2.8-fold and 1.7-fold respectively). It is concluded that low levels of IGF mRNAs can be detected using the solution hybridization assay and that there are considerable species differences within and between tissues with regard to steady-state levels of IGF-I and IGF-II mRNAs.
J Mol Endocrinol 1991 Dec
PMID:Quantitative comparison of insulin-like growth factor mRNA levels in human and rat tissues analysed by a solution hybridization assay. 177 43

Although the structure of several members of the GH receptor family has been defined, signal transduction following GH binding to its receptor has not been elucidated. Mouse osteoblasts were used to study the effect of GH on immediate early gene expression and, subsequently, the cellular signal(s) mediating this expression were analysed. GH rapidly and transiently induced the expression of c-jun and jun B in concert with the already reported expression of c-fos. The GH-induced expression of c-fos was completely blocked by the protein kinase inhibitors staurosporine and H7, indicating that the action of GH is mediated by one or several protein kinases. We next analysed the identity of the putative protein kinases in more detail by using a more specific protein kinase inhibitor, namely the ether-lipid 1-O-alkyl-2-O-methylglycerol, understood to be an inhibitor of protein kinase C (PKC). Data obtained from these studies revealed that GH-induced expression of c-fos is mediated by PKC. In addition, we observed a profound increase in formation of the PKC activator diacyglycerol upon addition of GH, a natural activator of PKC. In conclusion, upon binding of GH to mouse osteoblasts, the receptor-mediated cellular signal involves diacyglycerol formation and activation of PKC, leading to the induction of oncogene expression. Finally, the expression of c-fos, c-jun and jun B results in an increased binding of protein complexes to AP-1 binding sites.
J Mol Endocrinol 1991 Apr
PMID:Growth hormone induces expression of c-jun and jun B oncogenes and employs a protein kinase C signal transduction pathway for the induction of c-fos oncogene expression. 190 35


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