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

The objectives of the present studies were to determine if the numbers of IGF-I receptors in bovine granulosa cells differed with size of follicle and to determine if growth factors and hormones affected the number of IGF-I receptors in granulosa cells. Granulosa cells from small (1-5 mm) and large (> or = 8 mm) follicles were cultured for 2-4 days in 10% FCS and then assessed for levels of IGF-I receptors. Numbers of IGF-I receptors were 15-fold greater in granulosa cells from large than small follicles. In addition, bFGF (5 and 50 ng/ml) decreased whereas estradiol (1 microgram/ml), FSH (10 ng/ml) and EGF (10 and 100 ng/ml) increased the number of IGF-I receptors in granulosa cells from small follicles. These hormones had no effect on the number of IGF-I receptors in granulosa cells from large follicles. In conclusion, granulosa cells from large follicles have a greater number of IGF-I receptors than cells from small follicles, and thus, it appears that granulosa cells acquire a greater number of IGF-I receptors during the process of differentiation.
Mol Cell Endocrinol 1994 Jun
PMID:Insulin-like growth factor-I receptors in ovarian granulosa cells: effect of follicle size and hormones. 792 75

Plasma membrane purified from Buffalo rat liver tissue not only had the ability to bind 125I-EGF (2.77 pg of EGF/mg of membrane protein), but also exhibited both high (Kd = 0.08 nM) and low (Kd = 5.67 nM) affinity receptors. However, the binding of EGF to hepatoma plasma membrane was insignificant. EGF receptor in plasma membrane from normal liver tissue was identified by ECL Western blotting using monoclonal anti-EGF receptor antibody and phosphorylated via the stimulation of EGF. This phosphorylation was inhibited by genistein, a tyrosine kinase inhibitor. However, these effects were not observed in hepatoma cell membrane. These results suggest that plasma membrane purified from normal rat liver tissue has a high level of functional EGF receptor, whereas, hepatoma plasma membrane lacks the receptor.
Biochem Mol Biol Int 1994 May
PMID:Studies of epidermal growth factor (EGF) receptor in plasma membrane from rat liver and hepatoma tissues. 795 Oct 42

The blood-brain barrier GLUT1 glucose transporter is localized in brain to the capillary endothelium, which makes up the blood-brain barrier (BBB) in vivo. However, its expression is markedly downregulated in cultured bovine brain capillary endothelium (ECL cells), possibly due to the absence of brain-derived or astrocyte trophic factors in the tissue culture medium. To examine this hypothesis, we studied the effect of a bovine brain homogenate (BBH), and conditioned media and plasma membranes obtained from the rat C6 glioma cell line, on the abundance of the GLUT1 transcript in ECL cells. BBH induced a significant increase in the abundance of both GLUT1 and actin mRNAs, and this effect was dose and time dependent. The increase in the GLUT1 mRNA levels correlated with an increase in the transcriptional rate of this gene measured by nuclear run-on experiments. C6 conditioned media and C6 plasma membranes had no effect on the abundance of either GLUT1 or actin mRNA. To determine whether known growth factors cause BBH-like induction of GLUT1 and actin mRNAs, a series of growth factors was also tested. EGF and PDGF had no effect on the levels of these mRNAs. Basic FGF had a moderate effect and TNF alpha partially mimicked the effect of BBH on both GLUT1 and actin transcripts. The present data suggests that brain-derived trophic factors present in BBH stimulate BBB-GLUT1 glucose transporter gene expression in ECL cells through a transcriptional mechanism. Although this effect was partially mimicked by TNF alpha, C6 cell membranes or C6 conditioned media were unable to induce changes in the abundance of GLUT1 mRNA. Therefore, BBH may be a useful model to study the characterization of soluble brain-derived trophic factors involved in the induction of BBB-GLUT1 gene expression.
Brain Res Mol Brain Res 1994 Mar
PMID:Enhanced expression of the blood-brain barrier GLUT1 glucose transporter gene by brain-derived factors. 801 84

The regulation of growth factor receptors by protein kinase C was investigated in rat intestinal epithelial (RIE-1) cells. Short-term treatment of the cells with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, was employed to activate the kinase and longer-term exposure to the agent was used to assess the effects of protein kinase C depletion. Phorbol ester concentrations as low as 30 nM were found to down-regulate immunoreactive protein kinase C over 6 h, which correlated with the rapid loss of functional kinase activity. Whereas protein kinase C reduced the binding of 125I-labelled EGF, it increased the binding of 125I-labelled angiotensin II to RIE-1 cells. However, the kinase simultaneously inhibited the activation by angiotensin receptors of phosphatidylinositol 4,5 bisphosphate hydrolysis.
Biochem Mol Biol Int 1994 Feb
PMID:Regulation of growth factor receptors on rat intestinal epithelial (RIE-1) cells by protein kinase C. 801 36

Testosterone (T) is the major exogenous stimulus for the growth of prostatic carcinoma. It is believed that the proliferative action of T may be mediated by locally expressed growth modulatory factors. Recent evidence from our laboratory suggests that a LHRH (or a LHRH-like) loop might be expressed in human prostatic tumor cells. To verify this hypothesis, we have studied whether a mRNA for LHRH is expressed in the human androgen-responsive prostatic cancer cell line LNCaP, using the reverse transcription-polymerase chain reaction technique in the presence of a pair of specific oligonucleotide primers. A cDNA band of the expected size was obtained from LNCaP cells; this band hybridized with a 32P-labeled LHRH oligonucleotide probe and its sequence showed a complete match with the reported sequence of the human placental LHRH cDNA. These observations indicate that the mRNA coding for LHRH is expressed in LNCaP cells and suggest that a LHRH (or a LHRH-like) peptide might be produced by these cells. To clarify the possible action of this peptide, LNCaP cells were grown in a steroid-free medium and treated with a LHRH antagonist. The treatment resulted in a significant increase of tumor cell growth. These data clearly indicate that the LHRH system expressed in LNCaP cells plays an inhibitory role on cell proliferation, and that this system seems to be regulated in a negative way by steroids. An EGF/TGF alpha autocrine stimulatory loop (peptides, receptors, intracellular signals) is also functional in these cells. Treatment of LNCaP cells grown in serum-free conditions (i.e. in the absence of exogenous growth factors) with a monoclonal antibody against the EGF receptor, or with immunoneutralizing antibodies against EGF or TGF alpha, resulted in a significant decrease of cell proliferation. T positively regulates this EGF/TGF alpha system by increasing the concentration of EGF binding sites. The present data indicate that an inhibitory LHRH (or LHRH-like) system is expressed in LNCaP cells and participates in the local mechanisms regulating tumor cell proliferation together with an EGF/TGF alpha stimulatory loop. Both systems appear to be modulated by T.
J Steroid Biochem Mol Biol 1994 Jun
PMID:Androgen-dependent prostatic tumors: biosynthesis and possible actions of LHRH. 804 99

In parallel, we measured the receptor binding affinities for epidermal growth factor-urogastrone (EGF-URO) and transforming growth factor-alpha (TGF-alpha) in cultured smooth muscle (GCM) and epithelial (GPC) cells derived from guinea pig intestine. The relative order of binding affinities in the GCM cells was TGF-alpha > EGF-URO, in keeping with the relative order of biological potencies of these polypeptides in a guinea pig gastric circular muscle contractile bioassay. These data established by ligand binding criteria the presence of a TGF-alpha-preferring receptor in the guinea pig. In contrast, there was a reversed order of binding affinities (EGF-URO > TGF-alpha) for the polypeptides in GPC cells, in accord with an identical order of bioassay potencies previously observed in a guinea pig gastric longitudinal muscle contractile bioassay. Using a reverse transcription-polymerase chain reaction approach, we also cloned and sequenced putative EGF-URO receptor ligand binding domain III from each cell type. Although the binding specificity for TGF-alpha and EGF-URO differed in the GCM and GPC cells, the amino acid sequences of receptor domain III were identical in the two cell types. We conclude that the previously measured differences in biological potencies of EGF-URO and TGF-alpha in the contractile bioassay preparations are due to the distinct receptor binding affinities of EGF-URO and TGF-alpha that can be detected in different tissues. However, our data document that the distinct relative binding affinities for EGF-URO and TGF-alpha that can be observed in different cell types from the same species cannot be accounted for solely by the sequence of putative receptor ligand binding domain III.
Mol Pharmacol 1994 Aug
PMID:Ligand binding characterization and molecular analysis of distinct epidermal growth factor-urogastrone receptors in cultured smooth muscle and epithelial cells from guinea pig intestine. 807 89

Growth factors are known to regulate ovarian function. In the present study, effects of these growth factors, TGF-alpha, TGF-beta, and activin-A were tested on spontaneous porcine oocyte maturation. Cumulus-oocyte complexes (COC) were cultured in the presence of TGF-alpha, TGF-beta, and activin-A for 48 hr. Stages of meiotic maturation were assessed by staining with acetic orcein. Among these factors, only TGF-alpha significantly enhanced the maturation rate, whereas TGF-beta suppressed the spontaneous maturation rate. The site of action of TGF-alpha on COC and the interaction between TGF-alpha and EGF receptor was also examined. Denuded oocytes, alone or in coculture with cumulus cells, were cultured in the presence of TGF-alpha for 48 hr. TGF-alpha did not have any significant effect on denuded oocyte maturation. Heptanol was employed to investigate the role of gap junctions on TGF-alpha-induced oocyte maturation in COC. Although heptanol did not have any significant effect in the control medium, heptanol reversed the stimulatory effect of TGF-alpha on porcine oocyte maturation. TGF-alpha was able to displace 125I-EGF binding on COC. In conclusion, TGF-alpha enhances the spontaneous maturation of porcine oocytes by generating positive signal(s) in cumulus cells that are transferred to the oocyte via gap junctions. TGF-alpha shares the same receptor with EGF on porcine COC. TGF-beta, in contrast, inhibits porcine oocyte maturation.
Mol Reprod Dev 1994 Jun
PMID:Effects of transforming growth factors and activin-A on in vitro porcine oocyte maturation. 808 Jun 44

Recent findings have led to the concept that transforming growth factor alpha (TGF alpha) contributes to the neuroendocrine regulation of female puberty by stimulating the release of luteinizing hormone-releasing hormone (LHRH), the neurohormone controlling sexual development. It was postulated that this effect is mediated by epidermal growth factor receptors (EGFR) and that EGFR may not be located on LHRH neurons, so that TGF alpha-induced LHRH release would require an intermediate cell-to-cell interaction, presumably of glial-neuronal nature. The present study was undertaken to characterize the presence of EGFR in rat hypothalamus and to determine if changes in EGFR gene expression and EGFR protein occur at the time of puberty. RNA blot hybridization demonstrated that the hypothalamus expresses all mRNA species known to encode EGFR. RNase protection assays revealed that alternative splicing of the EGFR primary mRNA transcript occurs in the hypothalamus and produces a predominant transcript encoding the full-length EGFR and a much less abundant, shorter mRNA encoding a truncated, and presumably secreted form of EGFR. EGFR-like immunoreactive material was found in several hypothalamic regions including the organum vasculosum of the lamina terminalis, supraoptic, suprachiasmatic, and paraventricular nuclei, ependymal cells lining the third ventricle, some astrocytes associated with blood vessels, astrocytes of the pial surface, and tanycytes and glial cells of the median eminence (ME). Low levels of EGFR mRNA were detected by hybridization histochemistry in cells of the same areas containing EGFR-like immunoreactivity. Double-immunohistochemistry revealed that even though LHRH neurons are in close proximity to EGFR-positive cells, they do not contain EGFR. In the ME, EGFR-immunonegative LHRH nerve terminals tightly coexist with EGFR-positive cells, presumably tanycytes and glial astrocytes. EGFR mRNA levels measured by quantitative reverse transcription-polymerase chain reaction assay (RT-PCR) in the ME-arcuate nucleus region at the time of puberty decreased in the morning of the first proestrus, i.e., preceding the first preovulatory surge of gonadotropins, and rebounded at the time of the surge. Functional EGFR protein levels, detected by the ability of the receptor to autophosphorylate in response to ligand or divalent antibody-induced activation, changed in a similar manner at the time of puberty. No such changes were observed in the cerebellum, a brain region irrelevant to neuroendocrine reproductive control. These results demonstrate the existence of EGF receptors in the prepubertal female rat hypothalamus and suggest that changes in EGFR gene expression and biologically active EGFR protein contributes to the neuroendocrine process underlying the first preovulatory surge of gonadotropins.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Neurosci 1994 Jun
PMID:Expression of epidermal growth factor receptor changes in the hypothalamus during the onset of female puberty. 808 23

Dermal fibroblasts from nine Marfan syndrome patients with missense mutations in the fibrillin-1 gene (FBN1) produced nearly normal amounts of fibrillin as determined by quantitative pulse-chase experiments. However, six of the seven mutations involving substitutions of highly conserved cysteine residues exhibited lower rates of intracellular transport and secretion. This effect is likely due to improper folding, since intracellular fibrillin processing was also affected by the reducing agent dithiothreitol. Normal secretion patterns were seen in three mutations that either change the conformation of EGF-like domains or change consensus amino acids required for Ca(++)-binding. In all nine fibroblasts strains, however, the deposition of fibrillin in the extracellular matrix was reduced to 50% of normal in two and to less than 30% in seven of the nine samples studied. The protein alterations caused by these missense mutations are associated with moderate to severe features of Marfan syndrome and a dominant negative mechanism is suggested to play a major role in their pathogenesis.
Hum Mol Genet 1993 Dec
PMID:Missense mutations impair intracellular processing of fibrillin and microfibril assembly in Marfan syndrome. 811 84

Tumor necrosis factor-alpha (TNF) induces clustering of theca-interstitial cells (TIC) isolated from immature, hypophysectomized rats, while inhibiting luteinizing hormone (LH)-stimulated androstenedione in vitro. Stimulators of PKC, 1-oleoyl-2-acetyl-sn-glycerol (OAG, 50 and 100 microM) and phorbol-12-myristate-13-acetate (PMA, 50 nM), caused TIC clustering by 6 days in vitro. Clustering induced by these compounds resembled that induced by TNF. The protein kinase inhibitor, staurosporine at 1 and 10 nM, impaired TNF-induced TIC clustering for 6 days, as did the protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperizine dihydrochloride (H-7); conversely, the protein kinase inhibitor, chelerythrine chloride (0.1, 1.0 or 10 microM), did not attenuate TNF-directed clustering. The protein kinase inhibitors did not reverse the suppression of LH-stimulated androstenedione by TNF. Inhibitors of the EGF receptor PTK, A23 (10, 50, or 100 microM) and A46 (0.1, 1.0, 10, or 50 microM), impaired TNF-induced TIC clustering, while TNF suppression of LH-directed androstenedione was unaffected. EGF-induced TIC clustering was also impaired by A46, while A23 was less effective. Both A23 and A46 blocked EGF attenuation of LH-directed androstenedione after 4 days. When challenged with TNF (1 ng/ml) or PMA (50 nM), PKC activity increased in TIC. A23 (50 microM) and A46 (10 microM) each alone blocked the TNF-associated increase in PKC activity; however, PKC activity attributable to PMA was unaffected by A46. Together, these results suggest that TNF-induced TIC clustering involves activation of PTK which directs subsequent increases in PKC activity; however, mechanisms by which TNF inhibits LH-stimulated steroidogenesis remains elusive.
Mol Cell Endocrinol 1993 Nov
PMID:Involvement of protein kinase C and protein tyrosine kinase pathways in tumor necrosis factor-alpha-induced clustering of ovarian theca-interstitial cells. 814 4


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