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Regulation of the Pituitary Gland by Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
The regulation of FSH production and release is multifaceted. The major stimulator of FSH synthesis and release is hypothalamic GnRH, while gonadal steroids provide feedback information that can be inhibitory or stimulatory, depending on the physiological conditions. The gonads also produce three dimeric proteins—inhibin, activin, and follistatin—which exert a direct effect on FSH secretion from the gonadotrophs without affecting LH. Although the primary source of inhibin is the gonads of both sexes, both activin and follistatin are produced in extragonadal tissues, including the anterior pituitary, and can affect FSH through an autocrine/paracrine mechanism. Activin can influence the gonadotropins at many levels. First, it directly stimulates FSH biosynthesis and release from the gonadotrophs. Second, it up-regulates GnRHR gene expression, leading to alterations in the synthesis and release of both gonadotropins in response to GnRH. Third, activin can stimulate GnRH release from GnRH neurons, thereby affecting both FSH and LH secretion. Inhibin and follistatin negatively affect these effects by preventing the binding of activin to its receptor at the cell membrane, and by blocking the activation of downstream signal transduction pathways.
Participation of Cytokines and Growth Factors in Biliary Epithelial Proliferation and Mito-Inhibition during Ductular Reactions
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Anthony J. Demetris, J.G. Lunz, Vladimir Subbotin, Tong Wu, Isao Nozaki, Sarah Contrucci, Xia Yin
In vitro, BEC can produce TGF (beta) mRNA and protein and express the ligand-binding T(beta)R-II.40 Stimulation of cultured BEC with TGF(beta) results in the phosphorylation of SMAD2 and production of p21 protein, which inhibits cell cycle progression.40 In vivo, TGF (beta) 1 is produced primarily by stellate and inflammatory cells, but also by BEC in diseased livers.166,167 TGF(beta)2 is produced primarily by BEC in fibrotic livers.168 Activin A is produced by hepatocytes in normal liver and in stellate cells in diseased livers, particularly at the edge of regenerative nodules. This is the site of ongoing hepatocyte necrosis and ductular reactions.169 After BDL, the BEC stain strongly for TGF(beta)l protein102,167 and its mRNA is upregulated56 at 1 and 4 weeks after ligation, consistent with the down regulation of BEC proliferation at this time.78 In addition, the mannose 6-phosphate/insulin-like growth factor II receptor, which facilitates proteolytic activation of TGF (beta) 1, is also up-regulated in hyperplastic BEC at 1 and 4 weeks after ligation. TGF(beta) 1 may also play a role in morphogenesis as no apical polarization is seen in livers with biliary atresia, compared to the normal embryonic biliary tree.170 TGF(beta)1 can also inhibit progenitor cell proliferation.
Genetics of Endocrine Disorders and Diabetes Mellitus
Published in George H. Gass, Harold M. Kaplan, Handbook of Endocrinology, 2020
Bess Adkins Marshall, Abby Solomon Hollander
Several factors that regulate GH production do so through their effects on GHF-1 expression. Factors that increase the intracellular cAMP in the somatotroph will increase GHF-1 expression, whereas those that decrease intracellular cAMP will attenuate GHF-1. When GRF binds to its receptor on the somatotroph, it causes an increase in intracellular cAMP.17 GRFR is known to belong to the family of Gs-linked cell surface receptors.18 Somatostatin, however, has the opposite effect on intracellular cAMP and is a negative regulator of GH secretion. Somatostatin binds to a receptor that belongs to the family of Gi-linked cell surface receptors.18 Activin is a hormone synthesized in the pituitary gonadotrophs. It is known to stimulate follicle-stimulating hormone (FSH) secretion, but also acts as a negative regulator of GH. Activin binds to the distal GHF-1 binding site and reduces binding of GHF-1 to its recognition elements. Because activin down-regulates GH through a different mechanism than somatostatin, their suppressive effects are additive.19
Common therapeutic advances for Duchenne muscular dystrophy (DMD)
Published in International Journal of Neuroscience, 2021
Arash Salmaninejad, Yousef Jafari Abarghan, Saeed Bozorg Qomi, Hadi Bayat, Meysam Yousefi, Sara Azhdari, Samaneh Talebi, Majid Mojarrad
Myostatin is mainly expressed in skeletal muscles and in small amount in adipose tissue Moreover, myostatin forms complex with different proteins such as myostatin propeptide and its inhibitor, follistatin [200]. Follistatin acts as an antagonist of myostatin and its absence leads to muscle mass reduction. Overexpression of follistatin by delivering its gene via AAV vector into muscle resulted in muscle growth [201]. Follistatin also binds to activin A and B and other TGF-β family members, in this line, it also known as an activin-binding protein. Activin A is a muscle atrophy inducer. It is demonstrated that follistatin interacts with activin A and also myostatin and inhibits their activity which leads to increased muscle mass. In addition, it reduces inflammation, and regeneration and recovery of muscle is rapid [202]. It showed in phase I and IIa pre-clinical trials that intramuscular injection of specific follistatin isoform (FS344) by AAV gene delivering, improved the distance walk in 6MWT at Becker muscular dystrophy (BMD) patients [203].
Activin A overexpression promotes rat follicular development through SCF-kit-mediated cell signals
Published in Gynecological Endocrinology, 2020
Yuxia Wang, Luo Shuang, Su Yujie, Ma Xiaohui, Wang Wei, Wang Jidong
The molecular mechanism of follicular development is an unusually complex network system, the details of which are unclear. Activin A is mainly secreted by granulosa cells (paracrine) in the ovaries and has been reported to play a role in promoting cell proliferation and differentiation [1,2]. We predicted that activin A promotes the proliferation of ovarian granulosa cells (GCs). However, the activin A-mediated signaling pathway has not been determined and may involve protein molecules such as Smad2/3, MEK5, ERK5, and Nur77 [3,4]. Some studies showed that the SCF/C-kit signaling system is important in follicular development. Stem cell factor (SCF; also known as kit ligands) is produced by ovarian GCs and functions with the C-kit protein in oocytes. C-kit protein is a tyrosine kinase receptor on the surface of oocytes [5]. SCF and C-kit exert their functions after binding and activation. C-kit is activated by autologous phosphorylation to trigger downstream signal transduction cascade reactions [3,6]. There are specific phosphorylated tyrosine residue sites in C-kit molecules, which can be specifically combined with other signaling proteins [7]. Although SCF and C-kit play an important role in follicular development, their specific mechanism has not been widely examined.
Generation of high-yield insulin producing cells from human-induced pluripotent stem cells on polyethersulfone nanofibrous scaffold
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Reyhaneh Nassiri Mansour, Ghasem Barati, Masoud Soleimani, Pegah Ghoraeian, Maryam Nouri Aleagha, Mousa Kehtari, Hossein Mahboudi, Fatemeh Hosseini, Hadi Hassannia, Mohammad Foad Abazari, Seyed Ehsan Enderami
Different growth factors including EGF, bFGF, betacellulin and activin A were used in this study to differentiate hiPSCs into insulin-secreting cells. Different studies showed that EGF and bFGF which play important roles in cell proliferation and survival have a key role in pancreatic lineage neogenesis. These growth factors were secreted from endocrine precursors during islet neogenesis and used as chemo-attractants in islet cell clustering [36–38]. Activin A is a member of the transforming growth factor-beta (TGF-β) superfamily. This protein increases proliferation of beta and ductal-cells during pancreas development, as well as enhancing insulin secretion in response to glucose stimuli [39]. It is observed that Activin A could induce high expression of endocrine genes including Pdx-1, insulin and glucagon in mouse embryonic stem cells [40]. Some studies showed that betacellulin as an EGF family could promote differentiation of the different types of stem cells into insulin-secreting cells [41,42]. One of the factors used in this study to IPC differentiation of hiPSCs was a B27 supplement. B27 is used as a neural supplement and preserve neural cells characteristics in culture [43]. Different studies proved that stem cells can differentiate into IPCs in neural pathways [44,45]. As a result, this supplement could support pancreatic differentiation used in different IPC differentiation studies.