Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Interleukin-10 (IL-10) has a wide range of activities in the immune system such as modulation of interferon-gamma (IFN-gamma) and antibody production. The neuropeptide hormone corticotropin (ACTH) has similar activities, suggesting that a bidirectional communication mechanism operates between the immune and the neuroendocrine system involving these two substances. 2. Murine pituitary tumor cells (AtT-20) were found to produce up to 3 ng/ml of IL-10. 3. Pituitary cell corticotropin production was enhanced by IL-10 treatment. 4. IL-10 induced the production of ACTH in mouse splenocytes. 5. Authenticity of pituitary-derived IL-10 was shown by the demonstration of identical nucleic acid sequences of reverse-transcribed, polymerase chain reaction amplified fragments of cDNA obtained from murine splenocytes, a murine pituitary tumor cell line, and freshly isolated murine pituitaries.
Cell Mol Neurobiol 1994 Feb
PMID:Evidence for the production and action of interleukin-10 in pituitary cells. 795 60

LH is a dimeric glycoprotein hormone that is stored in the anterior pituitary and is released in response to GnRH, while the placental hormone, human CG (hCG), sharing the same alpha-subunit and a related beta-subunit, is secreted constitutively. In search of a determinant that allows sorting of LH into a regulated secretory pathway, the genes encoding the common alpha- and LH/CG beta-subunits were expressed in the GH3 rat pituitary tumor cell line, which contains a regulated secretory pathway. Steady state labeling and subsequent chase experiments showed that not only LH but also hCG can be sorted to a regulated secretory pathway; after an initial period of constitutive secretion, the mature forms of both hormones containing processed oligosaccharides were stored intracellularly, and their release was stimulated by either forskolin or KCl depolarization. In Chinese hamster ovary cells, which lack a regulated pathway and are devoid of storage granules, only hormones containing unprocessed N-linked oligosaccharides were found. In GH3 cells the LH beta-subunit was partially retained in an endoglycosidase H-sensitive form, presumably in the endoplasmic reticulum; the enzyme-resistant fraction was secreted through a regulated secretory pathway. A large fraction of the hCG beta-subunit was released constitutively, although some mature hCG beta-subunit accumulated in secretory granules and was released by forskolin. The common alpha-subunit was secreted constitutively with little intracellular accumulation of the mature forms. We conclude that the LH beta-subunit contains sufficient information to direct LH to a regulated pathway, and alpha:LH beta assembly is not a prerequisite for this targeting. The sorting of hCG to a regulated pathway in GH3 cells presumably reflects a structural similarity between LH and hCG. In addition, we have shown that GH3 cells can recognize the N-linked oligosaccharides on the gonadotropin subunits as substrates for sulfation.
Mol Endocrinol 1994 Jul
PMID:Human luteinizing hormone and chorionic gonadotropin are targeted to a regulated secretory pathway in GH3 cells. 798 53

The pituitary-specific transcription factor Pit-1 is required for expression of the PRL gene. Transcription of the PRL gene in the anterior pituitary is both activated and repressed in response to neuroendocrine signals. The molecular events that mediate repression are unknown. Transplantation of GH3 pituitary tumor cells from culture to female Wistar-Furth rats resulted in repression of PRL gene expression. When the transplanted cells were returned to culture, PRL gene expression was rapidly activated. We used this model to study potential mechanisms by which PRL gene expression was silenced. In addition to the appropriate size Pit-1 proteins of 33 and 31 kilodaltons, smaller forms of the transcription factor, migrating at approximately 27 and 24 kilodaltons, were found in transplanted cells in which PRL gene expression was repressed. These smaller forms of Pit-1 protein were observed to disappear when transplanted cells were returned to culture, coincident with the activation of PRL gene expression. A transcript approximately 170 base pairs shorter than expected for that encoding full-length Pit-1 was detected in transplanted GH3 cell RNA by polymerase chain reaction. The shorter Pit-1 transcript was abundant only in GH3 cells after in vivo passage and was not readily detected in transplanted cells after as little as 12 h in culture. This shorter transcript was found to result from excision of sequence corresponding to exon IV and encodes a Pit-1 protein lacking 54 amino acids of the POU-specific domain. Gene transfer studies demonstrated this alternative form of Pit-1 inhibited PRL promoter activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1994 Mar
PMID:An alternatively spliced form of Pit-1 represses prolactin gene expression. 801 54

Transplantation of GH3 rat pituitary tumor cells that express both PRL and GH to female Wistar-Furth rats results in tumors that secrete only GH. We have used in vivo passage of GH3 cells as a model system to study specific repression of PRL. RNA blot hybridization revealed that PRL message was repressed 95% in cells transplanted to host animals compared to that in GH3 cells in culture. In contrast, there was little change in GH message in the transplanted cells, and there was a 4-fold increase in insulin-like growth factor-I transcript levels. When the transplanted cells were returned to cell culture, PRL mRNA levels increased rapidly, reaching levels similar to those in GH3 cells within 72 h. Gene transfer studies demonstrated a low level PRL promoter utilization in GH3 cells after in vivo passage, when endogenous PRL was repressed. Transfection of the transplanted cells maintained in culture for 96 h, when endogenous PRL was expressed, demonstrated increased PRL promoter activity. Messenger RNA levels for the transcription factor Pit-1 were equivalent in GH3 cells and cells after in vivo passage, and the presence of Pit-1 protein in extracts from transplanted cells was demonstrated by Western blot analysis. Electrophoretic gel mobility shift assays indicated that protein interactions with the PRL promoter were very different for extracts prepared from cells in which PRL was repressed compared to those from cells maintained in culture until PRL expression had recovered.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1994 Jan
PMID:Specific repression of rat prolactin gene expression in transplanted tumor cells. 815 27

Human PRL (hPRL) gene expression is controlled by cAMP and Ca2+. This control is mediated by two cis-elements: a Pit-1 binding site (-62 to -35) and sequence A (-110 to -85), present in the hPRL promoter. We have investigated whether protein phosphatases could be involved in this regulation. GC-type rat pituitary tumor cells were transfected with sequence -138 to -35 of the hPRL gene promoter, upstream from a thymidine kinase promoter and a chloramphenicol acetyltransferase (CAT) reporter gene. Addition of okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, stimulates transient expression of the CAT gene. The dose-response curve shows a maximal effect at 25 nM OA (2.2-fold stimulation above controls). The OA effect is also observed with a natural 4500-base pair hPRL promoter. A single copy of the hPRL promoter sequence -115 to -85 (sequence A) confers to a thymidine kinase-CAT construct an identical response to OA, whereas a single copy of the proximal Pit-1 binding site does not. Synergism is observed between cAMP and OA in activating PRL gene transcription. This synergism is also observed with a single copy of sequence A. The effect of cAMP is not mediated by an L-type Ca2+ channel, since addition of the Ca2+ channel antagonist verapamil does not decrease it, nor does complexing extracellular Ca2+ significantly reduce it. Furthermore, OA and the Ca2+ channel opener BAY K8644 exert additive effects.
Mol Endocrinol 1993 Aug
PMID:Okadaic acid, a protein phosphatase inhibitor, enhances transcription of a receptor gene containing sequence A of the human prolactin promoter. 823 16

Triiodothyronine (T3) dependent growth of GH1 rat pituitary tumor cells in serum-free defined culture requires apotransferrin (apoTf) (Sirbasku et al.: Mol. Cell. Endocrinol., 77:C47-C55, 1991). Diferric transferrin (2Fe.Tf) also is necessary as an iron source (Eby et al.: Anal. Biochem., 203:317-325, 1992). Further, T3 dependence is prevented by soluble Fe(III) addition to the medium (Sato et al.: In Vitro Cell. Dev. Biol., 27A:599-602, 1991). While our data suggested that apoTf caused growth by chelation of Fe(III), direct evidence was required. We used urea polyacrylamide gel electrophoresis along with autoradiography and Western immunoblotting to measure the Fe(III) content of growing GH1 cell cultures and identify the apoTf, mono-metal transferrins and 2Fe.Tf present. We found that apoTf per se did not cause growth but instead chelated inhibitory levels of Fe(III). In fact, apoTf need not be present at all provided that Fe(III) is reduced to < or = 0.6 microM. In addition, other protein and non-protein Fe(III) chelators were shown to be as effective as apoTf. Here, we report that pituitary cells are completely inhibited by > or = 1.2 microM Fe(III), which are concentrations which might be expected in many culture media and usually are not thought to influence growth. The high sensitivity of pituitary cells to Fe(III) suggests further study to determine what cellular functions are affected and how they interfere with thyroid hormone dependence.
 ...
PMID:Apotransferrin stimulation of thyroid hormone dependent rat pituitary tumor cell growth in serum-free chemically defined medium: role of FE(III) chelation. 836 Feb 62

Prolactin (PRL) gene expression is regulated through a complex network of signal transduction pathways activated by various hormones and growth factors. Estrogens regulate PRL gene transcription in vivo through both direct and indirect, protein synthesis-dependent, mechanisms. Therefore, we hypothesized that other stimulators of PRL gene transcription might also act via protein synthesis-dependent mechanisms. To test this hypothesis, we examined, in GH4C1 rat pituitary tumor cells, the effects of protein synthesis inhibitors on the induction of PRL mRNA by known stimulators of PRL gene transcription. Whereas induction by epidermal growth factor (EGF) was abolished by cycloheximide and puromycin, increases in PRL mRNA caused by thyrotropin releasing hormone, 12-O-tetradecanoylphorbol 13-acetate, forskolin, or dibutyryl cyclic AMP were unaffected. These data suggest that the induction of PRL mRNA by EGF may require the induced synthesis of an intermediary regulatory protein.
Mol Cell Endocrinol 1993 Apr
PMID:Epidermal growth factor induces prolactin mRNA in GH4C1 cells via a protein synthesis-dependent pathway. 839 91

We produced four transgenic founder rats (F0) by introducing into rat embryos a fusion gene, which consisted of rat growth hormone (GH) promoter containing with four copies of thyroid hormone response element (TRE) and antisense cDNA sequences for rat GH. This transgene promoter directed 2.8-fold stimulation of CAT gene expression in transfected GH3 rat pituitary tumor cells compared with the rat GH promoter alone. Two of four transgenic rats expressed antisense RNA in the pituitary. Transgenic offspring (F1) from each founder rat exhibited dwarfism at as early as 3-4 weeks of age, and they exhibited approximately 70-85% reduced growth rate compared with their nontransgenic littermates over 56 weeks of observation. Plasma rat GH concentration was approximately 40-50% lower in transgenic F1 rats compared to their nontransgenic littermates. In these experiments, the pituitary hormone expression controlled in a complex manner was shown to be repressed by the antisense RNA transgene. Furthermore, the suppression of gene expression could be achieved by antisense RNA transgene in the rat as well.
Mol Reprod Dev 1993 Sep
PMID:Growth retardation in rats whose growth hormone gene expression was suppressed by antisense RNA transgene. 839 30

Rhodamine 123 is a fluorescent dye that localizes in mitochondria, is a substrate for the multidrug resistance pump, and is retained for long periods of time by carcinoma cells. 17 beta-Estradiol causes GH4C1 cells (rat pituitary tumor cells) to lose rhodamine 123 fluorescence faster than untreated cells. We found that estradiol induces accumulation of the mRNA for the multidrug resistance pump 3-5-fold, with maximum induction occurring within 1 day at 10(-9) M estradiol. Immunoblot analysis demonstrated that estradiol induces a protein of 150 kDa that reacts with an antibody to P-glycoprotein, the multidrug resistance pump. The reduced retention of rhodamine 123 caused by estradiol is prevented by verapamil and cyclosporin, inhibitors of the pump. A clone resistant to the effects of estradiol on rhodamine 123 has greatly reduced levels of mRNA for the pump. The effect of estradiol is more marked on rhodamine 123 retention than it is on that of rhodamine 110 or tetramethylrhodamine methyl ester. We conclude that estradiol enhances rhodamine 123 efflux by inducing the multidrug resistance gene. The specificity for rhodamine 123, compared with other analogs, may be caused by differences in accessibility to the pump.
Mol Pharmacol 1993 Jan
PMID:Estradiol induction of rhodamine 123 efflux and the multidrug resistance pump in rat pituitary tumor cells. 842 69

We have previously demonstrated that population density alters the responsiveness of GH4C1 pituitary tumor cells to 17 beta-estradiol (E2). At a low population density E2 was observed to increase prolactin mRNA and stimulate cell proliferation, whereas this estrogen was unable to elicit these responses when the cells were maintained at a 4-fold higher population density. In an attempt to determine the mechanism through which population density alters responsiveness to E2, the steady-state level of estrogen receptor (ER), the affinity of ER for E2, and ER down-regulation have been examined in both intact and fractionated cells using ligand binding and ligand exchange assays. Data presented herein demonstrate that (1) GH4C1 cells maintained at low density expressed fewer ER than cells cultured at high density; (2) ER in cells cultured at high density displayed a reduced affinity for E2; (3) ER down-regulation occurring within 1 h of E2 addition appeared to be more pronounced in high density cultures; and (4) steady-state levels of ER were similar in low and high density cells treated with E2 for 1 through 5 days. Although none of these observations appear to correlate with the previously observed effects of population density on the responsiveness of GH4C1 cells to E2, they further illustrate the potential of the culture environment to alter the responsiveness to estrogenic stimuli by altering the properties of the ER.
J Steroid Biochem Mol Biol 1993 Jan
PMID:Changes in population density elicit quantitative and qualitative changes in the estrogen receptor in intact GH4C1 pituitary tumor cells. 842 93


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