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)

Lactotropes in the pituitary gland might be useful models of how a cell type develops, differentiates, proliferates and regresses under the control of paracrine and autocrine signals. Lactotrope development during embryonic life is determined by a well-defined sequence of temporal and positional actions of locally produced members of the bone morphogenetic protein, hedgehog and fibroblast growth factor families. Transforming growth factor alpha (TGF-alpha), TGF-beta and galanin mediate the action of estrogen on the postnatal expansion of the lactotrope cell population and expression of the gene encoding prolactin in an autocrine/paracrine manner. Moreover, the classic hormone precursor pro-opiomelanocortin generates differentially glycosylated isoforms of its N-terminal fragment as paracrine controllers, which each induce distinct aspects of lactotrope differentiation and growth.
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PMID:Paracrine control of lactotrope proliferation and differentiation. 1271 80

Smad3, a critical component of the TGF-beta signaling pathways, plays an important role in the regulation of bone formation. However, how Smad3 affects osteoblast at the different differentiation stage remains still unknown. In the present study, we examined the effects of Smad3 on osteoblast phenotype by employing mouse bone marrow ST-2 cells and mouse osteoblastic MC3T3-E1 cells at the different differentiation stage. Smad3 overexpression significantly inhibited bone morphogenetic protein-2 (BMP-2)-induced ALP activity in ST-2 cells, indicating that Smad3 suppresses the commitment of pluripotent mesenchymal cells into osteoblastic cells. Smad3 increased the levels of COLI and ALP mRNA at 7 day cultures in MC3T3-E1 cells, and its effects on COL1 were decreased as the culture periods progress, although its effects on ALP were sustained during 21 day cultures. Smad3 overexpression enhanced the level of Runx2 and OCN mRNA at 14 day and 21 day cultures. Smad3 increased the levels of MGP and NPP-1 mRNA, although the extent of increase in MGP and NPP-1 was reduced and enhanced during the progression of culture period, respectively. Smad3 did not affect the level of ANK mRNA. On the other hand, Smad3 enhanced the level of MEPE mRNA at 14 and 21 day cultures, although Smad3 decreased it at 7 day cultures. In conclusion, Smad3 inhibits the osteoblastic commitment of ST-2 cells, while promotes the early stage of differentiation and maturation of osteoblastic committed MC3T3-E1 cells. Also, Smad3 enhanced the expression of mineralization-related genes at the maturation phase of MC3T3-E1 cells.
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PMID:Smad3 differently affects osteoblast differentiation depending upon its differentiation stage. 1711 1

Aldosterone production occurs in the adrenal cortex, and is regulated primarily by angiotensin II (Ang II), potassium and adrenocorticotropin (ACTH). In the presence of the aldosterone stimulators, steroidogenesis is further governed by local autocrine and/or paracrine factors in the adrenal cortex. We reported the presence of functional bone morphogenetic protein (BMP) system in the adrenal cortex and also demonstrated that BMP-6 increases Ang II-induced aldosterone production, which could be involved in the "aldosterone breakthrough" phenomenon. Aldosterone breakthrough is the phenomenon by which circulating aldosterone concentrations increase above pre-treatment levels after long-term therapy with ACE inhibitors or Ang II type 1 receptor antagonists (ARB). This phenomenon may lead to important clinical consequences since increased aldosterone in a high-salt state facilitates cardiovascular and renal damage in hypertensive patients. We found that long-term ARB treatment reverses the reduction of aldosterone synthesis by adrenocortical cells, thereby causing "cellular aldosterone breakthrough". The availability of BMP-6 in the adrenal cortex may be at least partly involved in the occurrence of cellular escape from aldosterone suppression under chronic treatment with ARB.
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PMID:Roles of bone morphogenetic protein-6 in aldosterone regulation by adrenocortical cells. 2080 37

The existence of a functional bone morphogenetic protein (BMP) system in the pituitary has been recognized. Recent studies have provided evidence that BMPs elicit differential actions in the regulation of prolactin (PRL) and adrenocorticotropin (ACTH) release in lactotropinoma and corticotropinoma cells, respectively. BMPs play a key role in the modulation of somatostatin receptor (SSTR) sensitivity of lactosomatotrope cells in an autocrine/paracrine manner. In addition, SSTR action enhances BMP responsiveness in corticotrope cells. The functional link between BMP receptor signaling and SSTR actions may be crucial for individual tolerance to somatostatin analogs for controlling PRL and ACTH production. Adjustment of the endogenous SSTR sensitivity may be an effective strategy to inhibit the growth activity and hormonal productivity of intractable pituitary tumors.
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PMID:BMP action in the pituitary: its possible role in modulating somatostatin sensitivity in pituitary tumor cells. 2205 14

The role of melatonin, a regulator of circadian rhythm, in adrenocorticotropin (ACTH) production by corticotrope cells has not been elucidated. In this study, we investigated the effect of melatonin on ACTH production in relation to the biological activity of bone morphogenetic protein (BMP)-4 using mouse corticotrope AtT20 cells that express melatonin type-1 (MT1R) but not type-2 (MT2R) receptors. We previously reported that BMP-4 inhibits corticotropin-releasing hormone (CRH)-induced ACTH production and proopiomelanocortin (POMC) transcription by inhibiting MAPK signaling. Both melatonin and an MT1R/MT2R agonist, ramelteon, suppressed CRH-induced ACTH production, POMC transcription and cAMP synthesis. The inhibitory effects of ramelteon on basal and CRH-induced POMC mRNA and ACTH levels were more potent than those of melatonin. Treatment with melatonin or ramelteon in combination with BMP-4 additively suppressed CRH-induced ACTH production. Of note, the level of MT1R expression was upregulated by BMP-4 stimulation. The suppressive effects of melatonin and ramelteon on POMC transcription and cAMP synthesis induced by CRH were not affected by an MT2R antagonist, luzindole. On the other hand, BMP-4-induced Smad1/5/8 phosphorylation and the expression of a BMP target gene, Id-1, were augmented in the presence of melatonin and ramelteon. Considering that the expression levels of BMP receptors, ALK-3/BMPRII, were increased by ramelteon, MT1R action may play an enhancing role in BMP-receptor signaling. Among the MT1R signaling pathways including AKT, ERK and JNK pathways, inhibition of AKT signaling functionally reversed the MT1R effects on both CRH-induced POMC transcription and BMP-4-induced Id-1 transcription. Collectively, MT1R signaling and BMP-4 actions were mutually augmented, leading to fine-tuning of ACTH production by corticotrope cells.
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PMID:Melatonin receptor activation suppresses adrenocorticotropin production via BMP-4 action by pituitary AtT20 cells. 2370 23

Functional interaction of clock genes and pituitary hormones was investigated by focusing on bone morphogenetic protein (BMP)-4 and melatonin actions in anterior pituitary cells. A significant correlation between the mRNA expression of proopiomelanocortin (POMC) and Per2 was revealed in serial cultures of corticotrope AtT20 cells. Knockdown of Per2 expression by siRNA in AtT20 cells resulted in a significant reduction of POMC mRNA level with or without corticotropin-releasing hormone (CRH) stimulation. Treatments with BMP-4 and melatonin, both of which suppress POMC expression, reduced Per2 mRNA as well as protein levels in AtT20 cells. On the other hand, in lactosomatotrope GH3 cells, an expressional correlation was found between prolactin (PRL) and Clock mRNA levels, which was attenuated in the presence of forskolin treatment. The siRNA-mediated knockdown of Clock expression, but not that of Bmal1, significantly reduced PRL mRNA levels in GH3 cells. Interestingly, Clock mRNA and protein levels did not fluctuate with melatonin, BMP-4 or forskolin treatment, although Bmal1 expression was significantly increased by forskolin treatment. Collectively, a significant correlation between the expression of POMC and Per2 and that between PRL and Clock were uncovered in corticotrope and lactosomatotrope cells, respectively. Per2 expression was inhibited by POMC modulators including melatonin and BMP-4, while Clock expression was steadily maintained. Thus, the effects of melatonin and BMP-4 on clock gene expression may imply differential stability of circadian rhythms of adrenocorticotropin (ACTH) and PRL secreted from the anterior pituitary.
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PMID:Interaction of pituitary hormones and expression of clock genes modulated by bone morphogenetic protein-4 and melatonin. 2572 18

The regulation of energy balance involves complex processes in the brain, including coordination by hypothalamic neurons that contain pro-opiomelanocortin (POMC). We previously demonstrated that central bone morphogenetic protein (BMP) 7 reduced appetite. Now we show that a type 1 BMP receptor, BMPR1A, is colocalized with POMC neurons and that POMC-BMPR1A-knockout (KO) mice are hyperphagic, revealing physiological involvement of BMP signaling in anorectic POMC neurons in the regulation of appetite. Surprisingly, the hyperphagic POMC-BMPR1A-KO mice exhibited a lack of obesity, even on a 45% high-fat diet. This is because the brown adipose tissue (BAT) of KO animals exhibited increased sympathetic activation and greater thermogenic capacity owing to a reestablishment of energy balance, most likely stemming from a compensatory increase of BMPR1A in the whole hypothalamus of KO mice. Indeed, control animals given central BMP7 displayed increased energy expenditure and a specific increase in sympathetic nerve activity (SNA) in BAT. In these animals, pharmacological blockade of BMPR1A-SMAD signaling blunted the ability of BMP7 to increase energy expenditure or BAT SNA. Together, we demonstrated an important role for hypothalamic BMP signaling in the regulation of energy balance, including BMPR1A-mediated appetite regulation in POMC neurons as well as hypothalamic BMP-SMAD regulation of the sympathetic drive to BAT for thermogenesis.
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PMID:Reestablishment of Energy Balance in a Male Mouse Model With POMC Neuron Deletion of BMPR1A. 2904 Apr 44