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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anterior pituitary corticotropes increase in number after stimulation by adrenalectomy or corticotropin-releasing hormone (CRH). However, is this brought about by mitoses? Furthermore, as epidermal growth factor (EGF) is a potent secretagogue for corticotropes, is it also a mitogen? To address these questions, populations of corticotropes enriched to 88-97% by counterflow centrifugation were studied after growth in 0-10 nM CRH with and without 0.1-10 ng/ml EGF. Three types of assays were used to detect changes in mitotic cells or cell number. An enzyme immunoassay for bromodeoxyuridine uptake during DNA synthesis [bromodeoxyuridine (BrDU) uptake] detected a 3-fold increase in optical density readings in the presence of 0.5 nM CRH or EGF. Together the peptides increased the optical density to 4.8-fold basal levels. No further increases in BrDU uptake were seen with higher concentrations of CRH or EGF. Cytochemical detection of BrDU uptake by immunolabeled corticotropes showed BrDU in 18 +/- 2% of 3- to 5-day ACTH cells. In the presence of 0.5 nM CRH or 0.5 ng/ml EGF, this value increased to 37 +/- 3% or 34 +/- 2% of ACTH cells, respectively. Together CRH and EGF stimulated increases in mitotic activity so that 47 +/- 4% of the ACTH cells were labeled for BrDU after a 1-h exposure. Cell growth/cell death assays in 3-(4,5-dimethyltiazol-2-yl)2,5- diphenyl tetrazolium bromide were also used to detect changes in overall cell number or cell survival in the same groups of enriched corticotrope cultures. Both 0.5 nM CRH and 0.5 ng/ml EGF caused increases to 1.5- to 1.7-fold basal readings. However, higher concentrations did not stimulate increases in number, and their combined effects were not additive. These studies show that CRH and EGF can be mitogens for ACTH-bearing corticotropes, in a limited dose range. In a higher dose range, their differentiating effects may eliminate dividing cells and retard further growth of the population.
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PMID:Corticotropin-releasing hormone and epidermal growth factor: mitogens for anterior pituitary corticotropes. 789 69

A cell line has been established from human placentae at the first trimester of normal pregnancy. The cell line was obtained by culture of purified cytotrophoblast cells in serum-free medium supplemented with epidermal growth factor, insulin, dexamethasone and 0.1% bovine serum albumin. The cells can be subcultured for >30 passages in one to three splits. All the cells were mononuclear epithelial-like cells positive to cytokeratin 18, gonadotrophin-releasing hormone (GnRH), neuropeptide Y, neurotensin, leucine-enkephalin, dopamine and 5-hydroxytryptamine immunocytochemical staining. The cells secreted GnRH, progesterone and oestradiol (in the presence of testosterone) but little human chorionic gonadotrophin and no beta-endorphin. The cell line showed human karyotypes and had a population doubling time of 48 h in serum-free medium. However, the cells would stop growing in the medium containing fetal bovine serum. A normal cytotrophoblast cell line established in serum-free medium will be particularly useful in the study of cytotrophoblast cell proliferation and differentiation.
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PMID:Establishment and characterization of a cytotrophoblast cell line from normal placenta of human origin. 867 49

C-fos is an early expression oncogene that can be stimulated by a variety of regulators. It is expressed by subsets of all pituitary cells, with increased expression seen in proestrous rats. However, in freshly dispersed pituitary cells studied during different stages of the cycle, there is limited expression of fos by luteinizing hormone (LH) cells and little basal expression by cells with follicle-stimulating hormone (FSH) antigens. Proestrus is a time during which pituitary gonadotropes express peak levels of receptors for gonadotropin-releasing hormone (GnRH) and epidermal growth factor (EGF). We hypothesized that if GnRH or EGF stimulated fos activity in gonadotropes they would be most effective during the peak expression of their receptors. Anterior pituitaries were removed, cut into small pieces, and stimulated for 30 min. Total RNA was then collected and analyzed by Northern analysis. Both EGF and GnRH caused an increase in c-fos mRNA levels in the anterior pituitary gland compared with unstimulated pituitary glands assayed immediately after removal from the pituitary. However, the stimulatory effects were no greater than those seen with medium alone. This suggested that fos expression could be stimulated by local factors either in the pituitary or the medium itself. The second phase of the study focused on pituitary cells plated for 1 hr and then stimulated with EGF and GnRH for 15 min. Dual immunocytochemistry was done to learn which cell types expressed the fos proteins. After 15 min, EGF and GnRH both increased the percentages of fos-bearing cells above levels seen in medium alone. EGF stimulated fos proteins in subsets of FSH, adrenocorticotropin (ACTH), and growth hormone (GH) cells. GnRH increased fos proteins in subsets of ACTH and GH cells. These results suggest that EGF and GnRH may regulate fos expression, but not necessarily in gonadotropes. They also highlight the need for carefully timed experiments because endogenous factors in the pituitary itself may stimulate immediate early gene expression. (J Histochem Cytochem 46:935-943, 1998)
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PMID:Regulation of c-fos expression by EGF and GnRH in specific anterior pituitary cells from proestrous female rats. 967 43

Insight into the mechanisms of action of neurotrophic growth factors has been obtained through the identification and characterization of gene products that are regulated or modified at the transcriptional, translational, and/or posttranslational level in response to neurotrophin treatment. VGF (non-acronymic) was identified approximately 15 years ago as a nerve growth factor (NGF)-regulated transcript in rat PC12 pheochromocytoma cells. Subsequent studies have demonstrated that neurotrophins such as NGF and brain-derived neurotrophic factor induce vgf gene expression relatively rapidly in PC12 cells and cultured cortical neurons, respectively, in comparison to less robust regulation by epidermal growth factor (EGF) and insulin, growth factors which do not trigger the neuronal differentiation of PC12 cells. vgf gene expression is stimulated in vitro by NGF and the ras/map kinase signaling cascade through a CREB-dependent mechanism, while in vivo, VGF mRNA levels are regulated by neuronal activity, including long-term potentiation, seizure, and injury. Both the mRNA and encoded approximately 68-kDa protein (VGF) are selectively synthesized in neuroendocrine and neuronal cells. The predicted VGF sequence is rich in paired basic amino acid residues that are potential sites for proteolytic processing, and VGF undergoes regulated release from dense core secretory vesicles. Although VGF mRNA is synthesized widely, by neurons in the brain, spinal cord, and peripheral nervous system, its expression is particularly abundant in the hypothalamus. In addition, VGF peptides are found in hypophysial, adrenal medullary, gastrointestinal, and pancreatic endocrine cells, suggesting important neuroendocrine functions. Recent analysis of VGF knockout mice indeed demonstrates that VGF plays a critical role in the control of energy homeostasis. VGF knockout mice are thin, small, hypermetabolic, hyperactive, and relatively infertile, with markedly reduced leptin levels and fat stores and altered hypothalamic pro-opiomelanocortin, neuropeptide Y, and agouti-related peptide expression. Coupled with the demonstration that VGF mRNA levels are induced in the normal mouse hypothalamic arcuate nuclei in response to fasting, important central and peripheral roles for VGF in the regulation of metabolism are suggested. Here we review previous studies of VGF in the broader context of its newly recognized role in the control of energy balance and propose several models and experimental approaches that may better define the mechanisms of action of VGF.
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PMID:VGF: a novel role for this neuronal and neuroendocrine polypeptide in the regulation of energy balance. 1088 40

The mouse mahogany gene encodes a protein that is involved in the suppression of diet-induced obesity. We studied the ability of its widely conserved C-terminal fragment to cross the blood-brain barrier (BBB) in mice. Multiple-time regression analysis showed that the entry rate (K(i)) of (125)I-mahogany (1377-1428) from blood-to-brain was 5.5 x 10(-4) ml/g. min. After coinjection of unlabeled mahogany (1377-1428), the K(i) was significantly decreased, showing the self-inhibition characteristic of a saturable transport mechanism. The excess mahogany (1377-1428) did not change the influx rate of (99m)Tcalbumin, the vascular control, indicating a lack of disruption of the BBB. Statistically significant cross-inhibition was not seen with agouti-related protein (83-132), melanin-concentrating hormone, epidermal growth factor, leptin, a melanocortin-4 receptor antagonist, or alpha-melanocyte-stimulating hormone. HPLC showed that most of the injected (125)I-mahogany (1377-1428) reached the brain intact, and capillary depletion with washout showed that most of it reached the parenchyma. There was no brain-to-blood efflux system for mahogany (1377-1428) but rather retention after i.c.v. administration, and the octanol/buffer partition coefficient showed low lipophilicity. Thus, the results show that the C-terminal peptide product encoded by the mahogany gene crosses the BBB by a transport mechanism that is saturable. The ability of this system to be regulated indicates the therapeutic potential of mahogany (1377-1428) in the treatment of obesity.
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PMID:Mahogany (1377-1428) enters brain by a saturable transport system. 1090 Feb 42

1. Factors, produced within the anterior pituitary, act locally to influence many acute and developmental changes in neighbouring cells. 2. Broad spectra of factors and activities characterize these paracrine interactions. 3. Cleavage products of pro-opiomelanocortin, other than those that act as systemic hormones, are produced by neonatal gonadotrophs and these peptides stimulate mitosis and differentiation of lactotrophs. 4. Activins and follistatins exert opposing effects on gonadotrophs. The stimulatory activity of activins is modulated extracellularly through protein-protein interactions with follistatin. Within gonadotrophs, the stimulatory activity of activins is self-limiting through receptor-mediated stimulatory and inhibitory signal transduction pathways. 5. During the oestrous cycle, the interactions between gonadotroph cells and epidermal growth factor (EGF), acting as a local signal, occur on multiple levels. Levels of expression of EGF receptors on cells vary as a function of the cycle, as do EGF-induced changes in gene expression and proliferation of cells.
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PMID:Intrapituitary interactions: another level of endocrine regulation. 1123 33

The development and function of the primate adrenal cortex are characterized by rapid growth, high steroidogenic activity, and a particular morphological appearance. The fetal adrenal glands grow rapidly and exponentially and at term are similar in weight to adult adrenals. From birth to 1 year their mass is reduced as they undergo a process of differentiation. Growth then remains slow until age 7 years. Thereafter, growth accelerates and the adrenals reach adult weight by the end of puberty. In the first trimester of gestation, fetal adrenal growth is thought to be independent of adrenocorticotropic hormone (ACTH), but after 15 weeks, ACTH is absolutely required for normal morphological and functional development. Other factors of fetal and/or placental origin, acting independently of or in conjunction with ACTH, are also required. Basic fibroblast growth factor, epidermal growth factor/transforming growth factor beta, and insulin-like growth factor (IGF)-I and -II, all acting in an autocrine and/or paracrine fashion, have been postulated to stimulate fetal adrenal cell proliferation. Corticotropin-releasing hormone may also play an important role in primate fetal adrenal function, primarily at the end of gestation. Finally, the estrogens are also important in the development of the pituitary-adrenal axis in primates.
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PMID:Development and function of the human fetal adrenal cortex. 1251 Sep 85

Despite the existence of interspecies phenotypic variability, animal models have yielded valuable insights into human pituitary diseases. Studies on Snell and Jackson mice known to have growth hormone, prolactin and thyroid-stimulating hormone deficiencies involving the hypoplastic pituitary gland have led to identifying alterations of the pituitary specific POU homeodomain Pit-1 transcription factor gene. The human phenotype associated with rare mutations in this gene was found to be similar to that of these mice mutants. Terminal differentiation of lactotroph cells and direct regulation of the prolactin gene both require interactions between Pit-1 and cell type specific partners, including panpituitary transcriptional regulators such as Pitx1 and Pitx2. Synergistic activation of the prolactin promoter by Pitx factors and Pit-1 is involved not only in basal condition, but also in responsiveness to forskolin, thyrotrophin-releasing-hormone and epidermal growth factor. In corticotroph cells, Pitx1 interacts with Tpit. Tpit mutations have turned out to be the main molecular cause of neonatal isolated adrenocorticotrophin deficiency. This finding supports the idea that Tpit plays an essential role in the differentiation of the pro-opiomelanocortin pituitary lineage. The effects of Pit-1 are not restricted to hormone gene regulation because this factor also contributes to cell division and protects the cell from programmed cell death. Lentiviral vectors expressing a Pit-1 dominant negative mutant induced time- and dose-dependent cell death in somatotroph and lactotroph adenomas in vitro. Gene transfer by lentiviral vectors should provide a promising step towards developing an efficient specific therapeutic approach by which a gene therapy programme for treating human pituitary adenomas could be based.
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PMID:Pituitary transcription factors: from congenital deficiencies to gene therapy. 1687 62

Previous studies have shown that epidermal growth factor (EGF) stimulates the release of adrenocorticotropin (ACTH) in vivo and in vitro by amplifying the effects of corticotropen-releasing hormone (CRH). The aim of the present studies was to compare responses to EGF by corticotropes in an unseparated culture with those in cultures enriched to 90-93% ACTH-beta-endorphin cells (by counterflow centrifugation). Since EGF binding sites had been identified on growth hormone (GH) or prolactin (PRL) cells (9), the enriched corticotrope cultures were studied to learn if the abundant GH or PRL cells found in unseparated cultures were required to mediate the actions of EGF. In unseparated cultures, EGF (1 or 10 ng/ml) or CRH (1-5 nM) increased the percentages of ACTH cells from 9.5 to 15% and the percentage of cells labeled for POMC mRNA from 7.5 to 12% of the population. In enriched cultures, CRH and EGF increased the percentages of cells labeled for POMC mRNA from 70% to 90-94% of the population. EGF alone stimulated ACTH secretion in both the unseparated and enriched cultures by 1.2- to 2.2-fold. EGF amplified the effects of CRH by 30-40% in both unseparated and enriched cultures. In unseparated cultures grown in serum-free media, however, 1 ng/ml EGF did not amplify the effects of CRH and 10 ng/ml EGF partly abolished the CRH stimulation. In contrast, enriched cultures grown in serum-free media continued to respond to the growth factor. the secretory responses of corticotropes in enriched cultures were similar to those of their counterparts in the unseparated cultures. This indicates that the reduction in numbers of GH and PRL cells in the enriched cultures does not interfere with EGF actions on the corticotrope population.
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PMID:Epidermal growth factor enhances ACTH secretion and expression of POMC mRNA by corticotropes in mixed and enriched cultures. 1991 4

Precise cellular targeting of macromolecular cargos has important biotechnological and medical implications. Using a recently established 'protein stapling' method, we linked the proteolytic domain of botulinum neurotoxin type A (BoNT/A) to a selection of ligands to target neuroendocrine tumor cells. The botulinum proteolytic domain was chosen because of its well-known potency to block the release of neurotransmitters and hormones. Among nine tested stapled ligands, the epidermal growth factor was able to deliver the botulinum enzyme into pheochromocytoma PC12 and insulinoma Min6 cells; ciliary neurotrophic factor was effective on neuroblastoma SH-SY5Y and Neuro2A cells, whereas corticotropin-releasing hormone was active on pituitary AtT-20 cells and the two neuroblastoma cell lines. In neuronal cultures, the epidermal growth factor- and ciliary neurotrophic factor-directed botulinum enzyme targeted distinct subsets of neurons whereas the whole native neurotoxin targeted the cortical neurons indiscriminately. At nanomolar concentrations, the retargeted botulinum molecules were able to inhibit stimulated release of hormones from tested cell lines suggesting their application for treatments of neuroendocrine disorders.
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PMID:Stapling of the botulinum type A protease to growth factors and neuropeptides allows selective targeting of neuroendocrine cells. 2363 40


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