Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rdw rat (gene symbol: rdw) with hereditary dwarfism has been shown immunohistochemically to have subnormal numbers not only of GH- but also of prolactin- and thyrotrophin-positive cells. To characterize the dwarfism of this strain, the expression of pituitary hormone mRNAs was examined by Northern hybridization. The pituitary gland in the rdw rat expressed 30-100 times less GH and prolactin mRNAs than normal controls, whereas mRNAs for pro-opiomelanocortin and the alpha subunit of rat glycoprotein hormone revealed a significant increase. There was a non-significant difference in rat LH-beta subunit and FSH-beta subunit between normal and rdw rats. The suppressed expression of a pituitary-specific transcription factor, Pit-1, is considered to cause hereditary dwarfism in mouse strains Snell and Jackson, whose phenotypes resemble those of the rdw rat. In this study, however, no difference in mRNA expression for Pit-1 was found between rdw rats and controls. This work indicates that the rdw rat may not have the same genotype as the phenotypically similar dwarf mice, Snell, Jackson and Ames.
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PMID:Expression of mRNA coding for pituitary hormones and pituitary-specific transcription factor in the pituitary gland of the rdw rat with hereditary dwarfism. 822 39

The pituitary gland contains six distinct hormone-producing cell types that arise sequentially during organogenesis. The first cells to differentiate are those that express the pro-opiomelanocortin (POMC) gene in the anterior pituitary lobe. The other lineages, which appear later, include cells that are dependent on the POU factor Pit-1 and another POMC-expressing lineage in the intermediate pituitary lobe. Using AtT-20 cells as a model for early expression of POMC in the anterior pituitary, we have defined a regulatory element conferring cell specificity of transcription and cloned a cognate transcription factor. This factor, Ptx1 (pituitary homeo box 1), contains a homeo box related to those of the anterior-specific genes bicoid and orthodenticle in Drosophila, and Otx-1 and Otx-2 in mammals. Ptx1 activates transcription upon binding a sequence related to the Drosophila bicoid target sites. Ptx1 is the only nuclear factor of this DNA-binding specificity that is detected in AtT-20 cells, and it is expressed at high levels in a subset of adult anterior pituitary cells that express POMC. However, Ptx1 is expressed in most cells of Rathke's pouch at an early time during pituitary development and before final differentiation of hormone-producing cells. Thus, Ptx1 may have a role in differentiation of pituitary cells, and its early expression pattern suggests that it may have a role in pituitary formation. In the adult pituitary gland, Ptx1 appears to be recruited for cell-specific transcription of the POMC gene.
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PMID:Ptx1, a bicoid-related homeo box transcription factor involved in transcription of the pro-opiomelanocortin gene. 867 14

Somatotroph adenomas often secrete prolactin (PRL) besides growth hormone (GH) and are sometimes immunostained for other anterior pituitary hormones or their subunits, such as thyroid-stimulating hormone (TSH) beta-subunit and glycoprotein hormone alpha-subunit (alpha SU). However, somatotroph adenomas showing hypersecretion of adrenocorticotropic hormone (ACTH) are extremely rare. There have been, to our knowledge, only five published reports on somatotroph adenomas accompanied by excessive ACTH secretion. Here we report a case of intracavernously invading somatotroph macro-adenoma with high serum GH, PRL, and ACTH levels. We examined the case using immunohistochemistry (IHC), in situ hybridization (ISH), and cell culture, and confirmed GH, PRL, and ACTH, as well as alpha SU, production, and the expression of Pit-1 protein by the adenoma, which is known as a transcriptional factor for GH, PRL, and TSH, not for ACTH. Therefore, the presence of unknown transcriptional factor other than Pit-1, common to GH, PRL, and ACTH, may be speculated to be expressed in this adenoma. In our previous study, we had found plurihormonal mRNA expression, especially for ACTH, the beta-subunit of follicle-stimulating hormone and luteinizing hormone in some somatotroph adenomas, using non-radio-isotopic ISH, and suggested that these adenomas might be derived from plurihormonal primordial stem cells. Our present case is significant from the viewpoint of histogenesis of pituitary adenomas, because it further supports the cell origin of somatotroph adenomas from plurihormonal primordial stem cells, and moreover it suggests the presence of unknown transcriptional factor other than Pit-1, common to GH, PRL, and ACTH.
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PMID:A case of pituitary somatotroph adenoma with concomitant secretion of growth hormone, prolactin, and adrenocorticotropic hormone--an adenoma derived from primordial stem cell, studied by immunohistochemistry, in situ hybridization, and cell culture. 889 Sep 99

Several pituitary transcription factors have been identified in the last 3 years. They offer new insights into the processes that direct organogenesis, cell commitment, proliferation and differentiated function. All are DNA-binding proteins, but they have ties to different families of homeodomain proteins. They differ in their distribution and in the timing of their appearance and extinction. The Rathke's pouch homeobox protein (Rpx) has a paired-like homeodomain. In mice, it appears on embryonic day 8.5 (day e8.5) and is gone by day e14.5. Its targets for activation are unknown. Pituitary OTX has a tryptophan--phenylalanine--lysine motif in its homeodomain. It appears early and persists. It shows independent activation of the alpha-glycoprotein subunit (alpha-GSU) and pro-opiomelanocortin genes and co-operates with Pit-1 in activation of the growth hormone and prolactin genes. Pituitary Lim (P-Lim) protein also acts independently on the alpha-GSU gene, and acts in concert with Pit-1 to activate other genes. A fourth protein, termed the 'Prophet of Pit-1', or Prop-1, is the recently discovered cause of Ames dwarfism in mice. This paired-like protein is necessary for the subsequent expression of Pit-1 in somatotrophs, lactotrophs and thyrotrophs. Any or all of the newly discovered pituitary genes are candidates for mutations causing hypopituitarism in humans. As several are expressed transiently in tissues other than the pituitary during organogenesis, the phenotypes produced by mutations in these genes may prove to be complex.
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PMID:Genes regulating hypothalamic and pituitary development. 940 35

To elucidate the effects of synthetic salmon calcitonin (sCT) on the cells in the rat pituitary gland, we histopathologically and immunohistochemically examined the early changes after 4 or 13 weeks treatment with sCT 120 IU/kg. Focal proliferative lesions of the anterior pituitary glands were consistently found after treatment with sCT for 13 weeks. Histologically, the cells with the focal proliferative lesions were classified into the following three groups: 1) enlarged basophilic cell focus, 2) vacuolated cell focus and 3) chromophobe cell focus. These focal proliferative lesions had positive staining only for the alpha-subunit and failed to show Pit-1 protein immunoreactivity. The sCT treatment also increased the thickness of the pars intermedia. Hypertrophy of the pars intermediate cells was characteristically seen. Furthermore, Pit-1 protein immunoreactivity was clearly detected in the nuclei of the hyperplastic pars intermediate cells. All pars intermediate cells were equally stained by alpha- or beta-MSH and beta-endorphin in both vehicle- and sCT-treatment. No difference was seen. These findings strongly suggest a very close relationship between Pit-1 protein immunoreactivity and cellular proliferation induced by sCT.
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PMID:Immunoreactive pit-1 protein in hyperplastic pars intermedia induced by calcitonin of the rat pituitary gland. 1081 Dec 88

The pituitary is a complex gland and is composed of several cell types, each responsible for the production of specific hormones. In the past, it was thought that one cell could make only one hormone; the concept of plurihormonality was poorly understood. Plurihormonal adenomas were thought to be either composed of multiple cell types, each producing one hormone (plurimorphous adenomas) or composed of poorly differentiated cells that exhibited abnormal production of multiple hormones. However, the molecular factors that determine hormone production have now been identified as transcription factors that target specific hormone genes. These factors have clarified three main pathways of cell differentiation. ACTH-producing corticotrophs are determined by corticotropin upstream transcription-binding element (CUTE) proteins including neuroD1/beta 2. Bihormonal gonadotrophs require expression of steroidgenic factor (SF)-1. The complex family of Pit-1 expressing cells can mature into somatotrophs, mammosomatotrophs, lactotrophs or thyrotrophs with the additional expression of estrogen receptor (ER) alpha, which enhances PRL secretion, or thyrotroph embryonic factor (TEF) which stimulates TSH-beta production. The recognition of these molecular determinants of adenohypophysial cytodifferentiation has clarified the patterns of plurihormonality which have been recognized in pituitary adenomas and provide a framework for classification of these tumors.
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PMID:Molecular determinants of pituitary cytodifferentiation. 1108 Nov 94

The correlation of growth hormone (GH) mRNA abundance and expression of specific transcription factors was studied in pituitaries of panhypopituitary (Ames df/df and Snell dwJ/dwJ dwarf), isolated GH-deficient (lit/lit), and GH-overproducing (growth hormone-releasing hormone [GHRH] transgenic) mice compared with normal littermates. A fluorescence-based reverse transcriptase polymerase chain reaction assay was developed for seven target mRNAs: GH, prolactin (PRL), pro-opiomelanocortin (POMC), alpha-subunit of the glycoprotein hormones (alphaSU), Pit-1, Prop-1, and Zn-16. Amplification parameters for each of these primer pairs were determined in order to calculate initial mRNA transcript number. The reproducibility of the assay was found to be +/-10% for either Pit-1 or Zn-16 mRNAs measured in characterized murine GHFT1-5 somatotroph precursor cells. The cell extracts also showed an increased abundance of both Zn-16 and Pit-1 mRNAs when compared with whole pituitary extracts. Measurement of copy number in normal pituitaries showed that for every 10(6) GH or PRL mRNAs, there were 3 x 10(5) POMC, 4 x 10(4) alphaSU, 2 x 10(3) Pit-1, and only 70 Zn-16 or Prop-1 transcripts. Transcript abundance in GH-altered mice as a percentage of copy number per normal gland showed that POMC was significantly reduced in dwJ/dwJ (p < 0.01) and df/df (p < 0.05) mice. AlphaSU mRNA was reduced in df/df (p < 0.05), dwJ/dwJ (p < 0.05), and lit/lit (p < 0.05) mice, but not in GHRH-excess mice. PRL mRNA was not detected in dwarf mice, reduced to 52% of normal in lit/lit (p < 0.05), and unchanged in GHRH-excess animals. GH mRNA was not detected in dwarf mice, reduced to 1.3% in lit/lit (p < 0.005), and increased to 242% in GHRH-excess mice (p < 0.05). Pit-1 mRNA was not detected in dwarf mice, was 2.9% of normal in lit/lit (p < 0.005) mice, and increased to 200% in GHRH-excess mice (p < 0.05). Prop-1 was not present in dwarf mice, was decreased to 1.4% in lit/lit (p < 0.01), and increased to 223% in GHRH-excess mice (p < 0.05). Zn-16 abundance in df/df mice was significantly reduced (p < 0.05) to 4.8% of normals, to 6.3% of normals in dwJ/dwJ (p < 0.005), to 6.1% of normals in lit/lit (p < 0.005) mice, and significantly elevated in GHRH-excess mice to 197% (p < 0.05). Altered pituitary mRNA abundance was found for several products not previously measured, or thought not to be affected by these mutations. Correlation of GH mRNA abundance with transcription factor copy number showed a significant correlation for Pit-1, Prop-1, and Zn-16. These quantitative analyses provide the first in vivo evidence that Zn-16 mRNA abundance correlates with GH expression.
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PMID:Transcript abundance in mouse pituitaries with altered growth hormone expression quantified by reverse transcriptase polymerase chain reaction implicates transcription factor Zn-16 in gene regulation in vivo. 1216 26

A 53-year-old Japanese woman was diagnosed with Cushing's disease caused by a adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma on the basis of clinical an imaging data. The surgically resected tumor tissue was investigated histopathologically using immunohistochemical analysis of pituitary hormones. Our study revealed that the adenoma expressed not only ACTH but growth hormone (GH) in the tumor cells. Furthermore, immunohistochemical double staining showed that some adenoma cells were positive for both ACTH and GH. In situ hybridization for GH mRNA revealed that the adenoma cells produced GH as opposed to simply storing it. Although many pituitary adenomas produce multiple pituitary hormones, pituitary adenoma producing both ACTH and GH in the same adenoma cells, such as seen in this case, is extremely rare. To elucidate the molecular mechanism involved, we investigated the expression of transcription factors NeuroD1 and Pit-1 and found that both transcription factors were expressed in many tumor cells. This case report describes a very rare case of pituitary adenoma that produced both ACTH and GH. We propose a hitherto undescribed translineage expression of transcription factors as the basic mechanism of this unique functional differentiation.
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PMID:A case of Cushing's disease caused by pituitary adenoma producing adrenocorticotropic hormone and growth hormone concomitantly: aberrant expression of transcription factors NeuroD1 and Pit-1 as a proposed mechanism. 1237 58

Gnathostomes express a common proopiomelanocortin (POMC) gene in the pars distalis (PD) and the pars intermedia (PI) of the pituitary gland. In contrast, the sea lamprey Petromyzon marinus expresses one distinct gene in each lobe; proopiocortin (POC) encoding adrenocorticotropic hormone (ACTH) and beta-endorphin (END) is expressed in the PD and proopiomelanotropin (POM) encoding melanophore-stimulating hormone (MSH), and a different beta-END is expressed in the PI. We characterized the genomic structure of the sea lamprey POC and POM genes including their 5'-flanking regions. Both genes have two introns at positions similar to those of gnathostomes. Each exon encodes genetic information seen in the gnathostome POMC gene: exon 1 encodes an untranslated nucleotide sequence, exon 2 encodes a signal peptide and the N-terminal short part of POC or POM, and exon 3 encodes all other parts including ACTH, MSHs or beta-END. Intron-A of POM (2289 bp) is six times longer than that of POC (379 bp). The POM intron-A has three transposon-like sequences (TnL-1, -2, -3), the total length of which is 1781 bp, suggesting that it has expanded via the insertion of TnLs. The 5'-flanking region of the POC gene contains two TATA boxes, a CCAAT box, eight E boxes, STAT, RAIE, and one binding site each for Ptx1, Pit-1, and Tpit. The POM gene contains four TATA boxes, eight E boxes, three STATs, two RAIEs, two CRE-like elements, and one binding site for Pit1. However, there is virtually no similarity between the two genes in the distribution of the elements. The transcriptional regulation of POC and POM may have diverged with the functional differentiation of the two genes.
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PMID:Structures for the proopiomelanocortin family genes proopiocortin and proopiomelanotropin in the sea lamprey Petromyzon marinus. 1597 17

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


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