scholarly journals The Musashi1 RNA-Binding Protein Functions as a Leptin-Regulated Enforcer of Pituitary Cell Fate and Hormone Production

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A654-A654
Author(s):  
Jewel Banik* ◽  
Juchan Lim* ◽  
Hardy L Linda ◽  
Angela Katherine Odle ◽  
Gwen V Childs ◽  
...  
Keyword(s):  
Cell Fate ◽  
Anterior Pituitary ◽  
Binding Protein ◽  
Mrna Translation ◽  
Pituitary Cell ◽  
Pituitary Hormone ◽  
Hormone Production ◽  
Lineage Specification ◽  
Regulatory Phosphorylation ◽  
Translational Activation

Abstract The pituitary gland is the major endocrine organ that produces and secretes hormones in response to hypothalamic signals to regulate important processes like growth, reproduction, and stress. The anterior pituitary adapts to metabolic and reproductive needs by exhibiting cellular plasticity, resulting in altered hormone production and secretion. The adipokine, leptin, serves a critical role to couple energy status to pituitary function. We have recently reported that the cell fate determinant, Musashi, functions as a post-transcriptional regulator of target mRNA translation in the mouse pituitary and have speculated that Musashi may modulate pituitary cell plasticity. However, the underlying mechanisms governing such pituitary plasticity are not fully understood. Musashi is an mRNA binding protein that is required for self-renewal, proliferation, and to control the differentiation of stem and progenitor cells. We have recently shown that Musashi is expressed in Sox2+ pituitary stem cells and surprisingly, we also found Musashi expression in all differentiated hormone expressing cell lineages in the adult anterior pituitary. The role of Musashi in these mature differentiated cells is unknown. We have observed that a range of critical pituitary mRNAs, including the lineage specification transcription factors Prop1 and Pou1f1, as well as hormone mRNAs including Tshb, Prl, and Gnrhr, all contain consensus Musashi binding elements (MBEs) in their 3’ untranslated regions (3’ UTRs). Using RNA electrophoretic mobility shift assays (EMSAs) and luciferase mRNA translation reporter assays we show that Musashi binds to these mRNAs and exerts inhibitory control of mRNA translation. Moreover, we determined that leptin stimulation opposes the ability of Musashi to exert translational repression of the Pou1f1 and Gnrhr 3’ UTRs. This de-repression does not require regulatory phosphorylation of Musashi on two conserved C-terminal serine residues. Interestingly in the same cell assay system, Musashi exerts translational activation of the Prop1 3’ UTR. We observed that this translational activation requires Musashi phosphorylation on the two regulatory C-terminal serine residues, consistent with the requirement for regulatory phosphorylation to drive translational activation of Musashi target mRNAs during Xenopus oocyte cell maturation. The distinction between MBEs in 3’ UTRs that exert repression (Pou1f1, Prl, Tshb, and Gnrhr) and the Prop1 3’ UTR that directs translational activation is under investigation. We propose that Musashi acts as a bifunctional regulator of pituitary hormone production and lineage specification and may function to maintain pituitary hormone plasticity in response to changing organismal needs.

scholarly journals Estrogen mediates sex differences in preoptic neuropeptide and pituitary hormone production in medaka

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Junpei Yamashita ◽  
Yuji Nishiike ◽  
Thomas Fleming ◽  
Daichi Kayo ◽  
Kataaki Okubo
Keyword(s):  
Anterior Pituitary ◽  
Pituitary Hormones ◽  
Pituitary Hormone ◽  
Sexually Dimorphic ◽  
Hormone Production ◽  
Anterior Pituitary Hormones ◽  
Vertebrate Brain ◽  
Pituitary Adenylate Cyclase ◽  
Evolutionarily Conserved ◽  
Sexually Dimorphic Expression

AbstractThe preoptic area (POA) is one of the most evolutionarily conserved regions of the vertebrate brain and contains subsets of neuropeptide-expressing neurons. Here we found in the teleost medaka that two neuropeptides belonging to the secretin family, pituitary adenylate cyclase-activating polypeptide (Pacap) and vasoactive intestinal peptide (Vip), exhibit opposite patterns of sexually dimorphic expression in the same population of POA neurons that project to the anterior pituitary: Pacap is male-biased, whereas Vip is female-biased. Estrogen secreted by the ovary in adulthood was found to attenuate Pacap expression and, conversely, stimulate Vip expression in the female POA, thereby establishing and maintaining their opposite sexual dimorphism. Pituitary organ culture experiments demonstrated that both Pacap and Vip can markedly alter the expression of various anterior pituitary hormones. Collectively, these findings show that males and females use alternative preoptic neuropeptides to regulate anterior pituitary hormones as a result of their different estrogen milieu.

scholarly journals History and perspectives of pituitary folliculo-stellate cell research

2005 ◽  
Vol 153 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Wilfried Allaerts ◽  
Hugo Vankelecom
Keyword(s):  
Cell Population ◽  
Anterior Pituitary ◽  
Hormone Secretion ◽  
Physiological Role ◽  
Pituitary Cell ◽  
Stem Cell Population ◽  
Cell Group ◽  
Pituitary Hormone ◽  
Topographical Distribution

Historically, the study of folliculo-stellate (FS) cells of the anterior pituitary dates back to the onset of electron microscopical observation of the pituitary gland. The morphological and electrophysiological characteristics, topographical distribution and contribution to intercellular junctions of these FS cells have been instrumental to the understanding of their putative function. Moreover, many studies have documented the role of FS cells as a source of newly discovered peptides, growth factors and cytokines. Quantitative immunohistochemical observation of FS cells in situ and functional in vitro studies, using either cultured FS cells or cells from an immortalized FS cell line, forwarded the notion of immunophenotypical and functional heterogeneity of the FS cell group. Double immunolabeling with a classical FS cell marker (S-100 protein) and with major histocompatibility complex class II markers characteristic for dendritic cells (DC) have shown a considerable overlap of FS cells with DC. The latter cells are immunocompetent cells belonging to the mononuclear phagocyte system. In this review, the FS cell heterogeneity is discussed with respect to the question of their embryological origin and developmental fate and with respect to the physiological relevance of functionally heterogeneous subpopulations. Recent findings of a myeloid origin of part of the interstitial cells of the anterior pituitary are confronted by other developmental paradigms of pituitary cell differentiation. The possibility that FS cells represent an adult stem cell population of the pituitary is critically examined. Also the physiological role of FS cells in the interferon-γ- and nitric oxide-mediated effects on pituitary hormone secretion is discussed. New approaches for the study of this enigmatic cell group using immortalized cell lines and new markers for an hitherto unrecognized pituitary cell population, the so-called ‘side population’, are evaluated.

scholarly journals The Cell Fate Determinant Musashi Is Controlled Through Dynamic Protein:Protein Interactions

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A555-A555
Author(s):  
Katherine Bronson ◽  
Meenakshisundaram Balasubramaniam ◽  
Linda Hardy ◽  
Gwen V Childs ◽  
Melanie C MacNicol ◽  
...  
Keyword(s):  
Cell Fate ◽  
Oocyte Maturation ◽  
Rna Binding ◽  
Mrna Translation ◽  
Hormone Production ◽  
Target Mrna ◽  
Associated Proteins ◽  
Specific Regulation ◽  
Partner Proteins

Abstract The Musashi RNA-binding protein functions as a gatekeeper of cell maturation and plasticity through the control of target mRNA translation. It is understood that Musashi promotes stem cell self-renewal and opposes differentiation. While Musashi is best characterized as a repressor of target mRNA translation, we have shown that Musashi can activate target mRNA translation in a cell context specific manner via regulatory phosphorylation on two evolutionarily conserved C-terminal serine residues. Our recent work has found that Musashi is expressed in pituitary stem cells as well as in differentiated hormone producing cell lineages in the adult pituitary. We hypothesize that Musashi maintains cell fate plasticity in the adult pituitary to allow the gland to modulate hormone production in response to changing organismal needs. Here, we seek to understand the regulation of Musashi function. Both Musashi isoforms (Musashi1 and Musashi2) contain two RNA-recognition motifs (RRMs) that bind to specific sequences in the 3’-UTR of target mRNA transcripts; however, neither isoform has enzymatic properties and thus functions through interactions with other proteins to regulate translational outcomes, but the identity and role of Musashi partner proteins is largely unknown. In this study, we have identified co-associated partner proteins that functionally contribute to Musashi-dependent mRNA translational activation during the maturation of Xenopus oocytes. Using mass spectrometry, we identified 29 co-associated proteins that interact specifically with Musashi1 during oocyte maturation and determined that the Musashi co-associated proteins ePABP, PABP4, LSM14A/B, CELF2, PUM1, ELAV1, ELAV2, and DDX6 attenuated oocyte maturation through individual antisense DNA oligo knockdowns. An assessment of the role of these cofactors in the control of Musashi-dependent target mRNA translation is in progress. In addition to studying co-associated proteins, we have created a computational 3D model of the Musashi1 molecule to assist in our investigation Musashi dimerization. This model has indicated that both Musashi1 dimerization and Musashi1:Musashi2 heterodimerization are energetically favorable, and co-pulldown studies have verified both Musashi1 homo-dimerization and Musashi1:Musashi2 heterodimerization in vivo. Computational modeling of Musashi dimer complexes has also identified the key amino acids necessary for these interactions. The contribution of each co-associated protein’s influence on Musashi-dependent translation, relative to the requirement for Musashi:Musashi dimerization, is expected to provide unparalleled insight into regulation of Musashi action. Moreover, cell type specific regulation of association of Musashi co-factors would directly influence Musashi target mRNA translation in oocyte maturation and during pituitary cell plasticity.

Vasoactive intestinal peptide, but not pituitary adenylate cyclase-activating peptide, modulates the responsiveness of the gonadotroph to LHRH in man

1993 ◽  
Vol 137 (3) ◽  
pp. 529-532 ◽  
Author(s):  
P. J. Hammond ◽  
K. Talbot ◽  
R. Chapman ◽  
M. A. Ghatei ◽  
S. R. Bloom
Keyword(s):  
Adenylate Cyclase ◽  
Vasoactive Intestinal Peptide ◽  
Anterior Pituitary ◽  
Pituitary Cell ◽  
Pituitary Hormone ◽  
Healthy Male ◽  
Anterior Pituitary Hormone ◽  
Pituitary Adenylate Cyclase ◽  
Releasing Factors ◽  
Lhrh Test

ABSTRACT Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are hypothalamic peptides sharing considerable sequence homology which are postulated to be hypophysiotrophic releasing factors. When infused into man, PACAP has no effect on anterior pituitary hormone levels, while VIP causes a significant increase in circulating prolactin concentrations. However, PACAP has recently been shown to augment the release of LH and FSH in response to LHRH in rat anterior pituitary cell culture. In order to ascertain if either peptide has a similar effect in man, PACAP and VIP were infused at 3·6 pmol/kg per min into six healthy male volunteers, and an LHRH test was performed 30 min after the infusion was commenced. Infusion of PACAP did not alter the gonadotrophin response to LHRH significantly. However, VIP augmented the release of LH significantly, both during the infusion and for 30 min thereafter, although there was no effect on FSH release. Thus VIP, but not PACAP, potentiates the release of LH after LHRH injection in man. Journal of Endocrinology (1993) 137, 529–532

scholarly journals Musashi interaction with poly(A)-binding protein is required for activation of target mRNA translation

2019 ◽  
Vol 294 (28) ◽  
pp. 10969-10986 ◽  
Author(s):  
Chad E. Cragle ◽  
Melanie C. MacNicol ◽  
Stephanie D. Byrum ◽  
Linda L. Hardy ◽  
Samuel G. Mackintosh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Oocyte Maturation ◽  
Binding Protein ◽  
Control Cell ◽  
Ectopic Expression ◽  
Mrna Translation ◽  
Stem Cell Differentiation ◽  
Target Mrna ◽  
Target Mrnas ◽  
Translational Activation

The Musashi family of mRNA translational regulators controls both physiological and pathological stem cell self-renewal primarily by repressing target mRNAs that promote differentiation. In response to differentiation cues, Musashi can switch from a repressor to an activator of target mRNA translation. However, the molecular events that distinguish Musashi-mediated translational activation from repression are not understood. We have previously reported that Musashi function is required for the maturation of Xenopus oocytes and specifically for translational activation of specific dormant maternal mRNAs. Here, we employed MS to identify cellular factors necessary for Musashi-dependent mRNA translational activation. We report that Musashi1 needs to associate with the embryonic poly(A)-binding protein (ePABP) or the canonical somatic cell poly(A)-binding protein PABPC1 for activation of Musashi target mRNA translation. Co-immunoprecipitation studies demonstrated an increased Musashi1 interaction with ePABP during oocyte maturation. Attenuation of endogenous ePABP activity severely compromised Musashi function, preventing downstream signaling and blocking oocyte maturation. Ectopic expression of either ePABP or PABPC1 restored Musashi-dependent mRNA translational activation and maturation of ePABP-attenuated oocytes. Consistent with these Xenopus findings, PABPC1 remained associated with Musashi under conditions of Musashi target mRNA de-repression and translation during mammalian stem cell differentiation. Because association of Musashi1 with poly(A)-binding proteins has previously been implicated only in repression of Musashi target mRNAs, our findings reveal novel context-dependent roles for the interaction of Musashi with poly(A)-binding protein family members in response to extracellular cues that control cell fate.

PITUITARY HORMONE PRODUCTION AND RELEASE IN THE THYROIDECTOMIZED RAT AFTER THYROXINE ADMINISTRATION

1963 ◽  
Vol 42 (2) ◽  
pp. 275-292 ◽  
Author(s):  
A. N. Contopoulos ◽  
A. A. Koneff ◽  
J. D. Jameson
Keyword(s):  
Effective Dose ◽  
Normal Control ◽  
Anterior Pituitary ◽  
Female Rats ◽  
Pituitary Hormone ◽  
Hormone Production ◽  
Minimal Effective Dose ◽  
Thyrotrophic Hormone ◽  
Hormonal Content ◽  
Long Evans

ABSTRACT Female rats of the Long-Evans strain were thyroidectomized at 35–40 days of age and 56 days later were placed into three groups each receiving injections 1, 2 or 3 μg of thyroxine per day for four days. Uninjected thyroidectomized and normal rats were used as controls. Twenty-four hours after the last injection the pituitaries and plasma were bio-assayed as a measure of pituitary hormone production and secretion. The minimal effective dose in hypophysectomized recipients in terms of whole anterior pituitary, or fraction thereof, are as follows: normal control pituitary – TSH, 1/16; FSH, < 3; ICSH, 1; GH> 1/16; thyroidectomy – TSH, 1/8–1/4; FSH, > 5; ICSH, > 5; GH, 3. Thyroxine administration restored the TSH pituitary content to normal at 1 μg dose, and increased it further at the 2 and 3 μg dose. The pituitary content of GH increased from the post-thyroidectomy levels to near normal levels with increasing doses of thyroxine. The ICSH content of the pituitary was influenced by the administration of thyroxine but no effect was obvious in FSH content. GH was not detectable in plasma of thyroidectomized rats but was present in the plasma of animals receiving 2 or 3 μg of thyroxine. Thyrotrophic hormone content of plasma was decreased after administration of thyroxine. Gonadotrophin was not detected in any plasma. The above changes in hormonal content preceded the reappearance of normal pituitary cytology.

scholarly journals Effects of Melatonin on Anterior Pituitary Plasticity: A Comparison Between Mammals and Teleosts

2021 ◽  
Vol 11 ◽  
Author(s):  
Elia Ciani ◽  
Trude M. Haug ◽  
Gersende Maugars ◽  
Finn-Arne Weltzien ◽  
Jack Falcón ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Pituitary Hormones ◽  
Future Research ◽  
Pituitary Hormone ◽  
Hormone Production ◽  
Physiological Processes ◽  
Important Target ◽  
Specific Receptors ◽  
Positive And Negative Feedback

Melatonin is a key hormone involved in the photoperiodic signaling pathway. In both teleosts and mammals, melatonin produced in the pineal gland at night is released into the blood and cerebrospinal fluid, providing rhythmic information to the whole organism. Melatonin acts via specific receptors, allowing the synchronization of daily and annual physiological rhythms to environmental conditions. The pituitary gland, which produces several hormones involved in a variety of physiological processes such as growth, metabolism, stress and reproduction, is an important target of melatonin. Melatonin modulates pituitary cellular activities, adjusting the synthesis and release of the different pituitary hormones to the functional demands, which changes during the day, seasons and life stages. It is, however, not always clear whether melatonin acts directly or indirectly on the pituitary. Indeed, melatonin also acts both upstream, on brain centers that control the pituitary hormone production and release, as well as downstream, on the tissues targeted by the pituitary hormones, which provide positive and negative feedback to the pituitary gland. In this review, we describe the known pathways through which melatonin modulates anterior pituitary hormonal production, distinguishing indirect effects mediated by brain centers from direct effects on the anterior pituitary. We also highlight similarities and differences between teleosts and mammals, drawing attention to knowledge gaps, and suggesting aims for future research.

scholarly journals Pit-1β reduces transcription and CREB-binding protein recruitment in a DNA context-dependent manner

2005 ◽  
Vol 185 (1) ◽  
pp. 173-185 ◽  
Author(s):  
A L Ferry ◽  
D M Locasto ◽  
L B Meszaros ◽  
J C Bailey ◽  
M D Jonsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Anterior Pituitary ◽  
Binding Protein ◽  
Regulation Of Gene Expression ◽  
Pituitary Hormone ◽  
Dependent Manner ◽  
Creb Binding Protein ◽  
Control Of Gene Expression ◽  
Protein Recruitment

Many transcription factors are expressed as multiple isoforms with distinct effects on the regulation of gene expression, and the functional consequences of structural differences between transcription factor isoforms may allow for precise control of gene expression. The pituitary transcription factor isoforms Pit-1 and Pit-1β differentially regulate anterior pituitary hormone gene expression. Pit-1 is required for the development of and appropriate hormone expression by anterior pituitary somatotrophs and lactotrophs. Pit-1β differs structurally from Pit-1 by the splice-insertion of the 26-residue β-domain in the trans-activation domain, and it differs functionally from Pit-1 in that it represses expression of the prolactin promoter in a cell-type specific manner. In order to identify signal and promoter context requirements for repression by Pit-1β, we examined its function in the presence of physiological regulatory signals as well as wild-type and mutant Pit-1-dependent target promoters. Here, we demonstrate that Pit-1β impairs recruitment of cAMP response element-binding protein (CREB)-binding protein to the promoters that it represses. In addition, we show that repression of target promoter activity, reduction in promoter histone acetylation, and decrease of CREB-binding protein recruitment all depend on promoter context. These findings provide a mechanism for promoter-specific repression by Pit-1β.

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