scholarly journals MicroRNA-7a2 Regulates Prolactin in Developing Lactotrophs and Prolactinoma Cells

Endocrinology ◽  
2020 ◽  
Vol 162 (2) ◽  
Author(s):  
Mary P LaPierre ◽  
Svenja Godbersen ◽  
Mònica Torres Esteban ◽  
Anaïs Nura Schad ◽  
Mathias Treier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mirna Family ◽  
Dynamic Network ◽  
Loss Of Function ◽  
Gradual Loss ◽  
Prolactin Gene ◽  
Multiple Cell ◽  
Complex Regulation ◽  
Mouse Pituitary ◽  
Shed Light

Abstract Prolactin production is controlled by a complex and temporally dynamic network of factors. Despite this tightly coordinated system, pathological hyperprolactinemia is a common endocrine disorder that is often not understood, thereby highlighting the need to expand our molecular understanding of lactotroph cell regulation. MicroRNA-7 (miR-7) is the most highly expressed miRNA family in the pituitary gland and the loss of the miR-7 family member, miR-7a2, is sufficient to reduce prolactin gene expression in mice. Here, we used conditional loss-of-function and gain-of-function mouse models to characterize the function of miR-7a2 in lactotroph cells. We found that pituitary miR-7a2 expression undergoes developmental and sex hormone–dependent regulation. Unexpectedly, the loss of mir-7a2 induces a premature increase in prolactin expression and lactotroph abundance during embryonic development, followed by a gradual loss of prolactin into adulthood. On the other hand, lactotroph development is delayed in mice overexpressing miR-7a2. This regulation of lactotroph function by miR-7a2 involves complementary mechanisms in multiple cell populations. In mouse pituitary and rat prolactinoma cells, miR-7a2 represses its target Raf1, which promotes prolactin gene expression. These findings shed light on the complex regulation of prolactin production and may have implications for the physiological and pathological mechanisms underlying hyperprolactinemia.

Age-Related Decrease of Growth Hormone and Prolactin Gene Expression in the Mouse Pituitary*

Endocrinology ◽  
1987 ◽  
Vol 121 (4) ◽  
pp. 1251-1255 ◽  
Author(s):  
MARK D. CREW ◽  
STEPHEN R. SPINDLER ◽  
ROY L. WALFORD ◽  
AKIO KOIZUMI
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Age Related ◽  
Prolactin Gene ◽  
Mouse Pituitary

scholarly journals Understanding biological ageing in terms of constitutive signals: Convergence to an average decrease in cellular sensitivity and information transmission

2019 ◽  
Author(s):  
Alvaro Martinez Guimera ◽  
Daryl P. Shanley
Keyword(s):  
Information Transmission ◽  
Biological Function ◽  
Loss Of Function ◽  
Biological Ageing ◽  
Average Decrease ◽  
Network Sensitivity ◽  
Gradual Loss ◽  
Cellular Sensitivity ◽  
Stochastic Damage ◽  
Shed Light

Biological ageing is a process that encompasses observations often too heterogeneous to draw coherent conceptual frameworks that may shed light into the generality of the underlying gradual loss of function. Whilst the concept of stochastic damage is often invoked as the driver of the ageing process, this can be too abstract to understand ageing at a higher mechanistic resolution. However, there do exist general mechanisms that describe how stochastic damage interferes with biological function, such as through genetic mutations. In a similar manner, we argue that a ‘molecular habituation’ phenomenon occurs during biological ageing where constitutive signals arising from damage accumulation drive an average decrease in network sensitivity and information transmission, as well as an increase in noise, across cells and tissue.

scholarly journals Actin-Related Protein 4 Interacts with PIE1 and Regulates Gene Expression in Arabidopsis

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 520
Author(s):  
Wenfeng Nie ◽  
Jinyu Wang
Keyword(s):  
Gene Expression ◽  
Plant Growth ◽  
Chromatin Remodeling ◽  
Leaf Size ◽  
Early Flowering ◽  
Physical Interaction ◽  
Loss Of Function ◽  
Single Nucleotide Change ◽  
Chromatin Remodeling Complex ◽  
Related Proteins

As essential structural components of ATP-dependent chromatin-remodeling complex, the nucleolus-localized actin-related proteins (ARPs) play critical roles in many biological processes. Among them, ARP4 is identified as an integral subunit of chromatin remodeling complex SWR1, which is conserved in yeast, humans and plants. It was shown that RNAi mediated knock-down of Arabidopsis thaliana ARP4 (AtARP4) could affect plant development, specifically, leading to early flowering. However, so far, little is known about how ARP4 functions in the SWR1 complex in plant. Here, we identified a loss-of-function mutant of AtARP4 with a single nucleotide change from glycine to arginine, which had significantly smaller leaf size. The results from the split luciferase complementation imaging (LCI) and yeast two hybrid (Y2H) assays confirmed its physical interaction with the scaffold and catalytic subunit of SWR1 complex, photoperiod-independent early flowering 1 (PIE1). Furthermore, mutation of AtARP4 caused altered transcription response of hundreds of genes, in which the number of up-regulated differentially expressed genes (DEGs) was much larger than those down-regulated. Although most DEGs in atarp4 are related to plant defense and response to hormones such as salicylic acid, overall, it has less overlapping with other swr1 mutants and the hta9 hta11 double-mutant. In conclusion, our results reveal that AtARP4 is important for plant growth and such an effect is likely attributed to its repression on gene expression, typically at defense-related loci, thus providing some evidence for the coordination of plant growth and defense, while the regulatory patterns and mechanisms are distinctive from other SWR1 complex components.

scholarly journals Identification of the functional components of the Ras signaling pathway regulating pituitary cell-specific gene expression.

1994 ◽  
Vol 14 (3) ◽  
pp. 1553-1565 ◽  
Author(s):  
K E Conrad ◽  
J M Oberwetter ◽  
R Vaillancourt ◽  
G L Johnson ◽  
A Gutierrez-Hartmann
Keyword(s):  
Gene Expression ◽  
Pituitary Cell ◽  
Mitogen Activated Protein Kinase ◽  
Specific Gene ◽  
Ras Signaling ◽  
Raf Kinase ◽  
Prolactin Gene ◽  
Ras Signaling Pathway ◽  
Mitogen Activated Protein ◽  
Prolactin Promoter

Ras, a small GTP-binding protein, is required for functional receptor tyrosine kinase signaling. Ultimately, Ras alters the activity of specific nuclear transcription factors and regulates novel patterns of gene expression. Using a rat prolactin promoter construct in transient transfection experiments, we show that both oncogenic Ras and activated forms of Raf-1 kinase selectively stimulated the cellular rat prolactin promoter in GH4 rat pituitary cells. We also show that the Ras signal is completely blocked by an expression vector encoding a dominant-negative Raf kinase. Additionally, using a molecular genetic approach, we determined that inhibitory forms of p42 mitogen-activated protein kinase and an Ets-2 transcription factor interfere with both the Ras and the Raf activation of the rat prolactin promoter. These findings define a functional requirement for these signaling constituents in the activation of the prolactin gene, a cell-specific gene which marks the lactotroph pituitary cell type. Further, this analysis allowed us to order the components in the Ras signaling pathway as it impinges on regulation of prolactin gene transcription as Ras-->Raf kinase-->mitogen-activated protein kinase-->Ets. In contrast, we show that intact c-Jun expression inhibited the Ras-induced activation of the prolactin promoter, defining it as a negative regulator of this pathway, whereas c-Jun was able to enhance the Ras activation of an AP-1-driven promoter in GH4 cells. These data show that c-Jun is not the nuclear mediator of the Ras signal for the highly specialized, pituitary cell-specific prolactin cellular promoter. Thus, we have defined a model system which provides an ideal paradigm for studying Ras/Raf signaling pathways and their effects on neuroendocrine cell-specific gene regulation.

scholarly journals Resilience, plasticity and robustness in gene expression during aging in the brain of outbred deer mice

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
E Soltanmohammadi ◽  
Y Zhang ◽  
I Chatzistamou ◽  
H. Kiaris
Keyword(s):  
Gene Expression ◽  
Cholesterol Metabolism ◽  
Expression Profiles ◽  
Deer Mice ◽  
Abrupt Changes ◽  
Transcriptional Changes ◽  
Thrombospondin 4 ◽  
Whole Transcriptome ◽  
The Brain ◽  
Shed Light

Abstract Background Genes that belong to the same network are frequently co-expressed, but collectively, how the coordination of the whole transcriptome is perturbed during aging remains unclear. To explore this, we calculated the correlation of each gene in the transcriptome with every other, in the brain of young and older outbred deer mice (P. leucopus and P. maniculatus). Results In about 25 % of the genes, coordination was inversed during aging. Gene Ontology analysis in both species, for the genes that exhibited inverse transcriptomic coordination during aging pointed to alterations in the perception of smell, a known impairment occurring during aging. In P. leucopus, alterations in genes related to cholesterol metabolism were also identified. Among the genes that exhibited the most pronounced inversion in their coordination profiles during aging was THBS4, that encodes for thrombospondin-4, a protein that was recently identified as rejuvenation factor in mice. Relatively to its breadth, abolishment of coordination was more prominent in the long-living P. leucopus than in P. maniculatus but in the latter, the intensity of de-coordination was higher. Conclusions There sults suggest that aging is associated with more stringent retention of expression profiles for some genes and more abrupt changes in others, while more subtle but widespread changes in gene expression appear protective. Our findings shed light in the mode of the transcriptional changes occurring in the brain during aging and suggest that strategies aiming to broader but more modest changes in gene expression may be preferrable to correct aging-associated deregulation in gene expression.

scholarly journals Comparative approaches to the study of physiology: Drosophila as a physiological tool

2013 ◽  
Vol 304 (3) ◽  
pp. R177-R188 ◽  
Author(s):  
Wendi S. Neckameyer ◽  
Kathryn J. Argue
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Pattern Formation ◽  
Signaling Pathways ◽  
Human Disease ◽  
Cognitive Disorders ◽  
Model System ◽  
Critical Questions ◽  
Developmental Signaling ◽  
Shed Light

Numerous studies have detailed the extensive conservation of developmental signaling pathways between the model system, Drosophila melanogaster, and mammalian models, but researchers have also profited from the unique and highly tractable genetic tools available in this system to address critical questions in physiology. In this review, we have described contributions that Drosophila researchers have made to mathematical dynamics of pattern formation, cardiac pathologies, the way in which pain circuits are integrated to elicit responses from sensation, as well as the ways in which gene expression can modulate diverse behaviors and shed light on human cognitive disorders. The broad and diverse array of contributions from Drosophila underscore its translational relevance to modeling human disease.

scholarly journals Role of Hypoxia-Mediated Autophagy in Tumor Cell Death and Survival

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 533
Author(s):  
Rania F. Zaarour ◽  
Bilal Azakir ◽  
Edries Y. Hajam ◽  
Husam Nawafleh ◽  
Nagwa A. Zeinelabdin ◽  
...  
Keyword(s):  
Cell Death ◽  
Type I ◽  
Dependent Manner ◽  
Destruction Process ◽  
Tumor Cell Death ◽  
Complex Regulation ◽  
Cancer Immunotherapies ◽  
The Relationship ◽  
Shed Light

Programmed cell death or type I apoptosis has been extensively studied and its contribution to the pathogenesis of disease is well established. However, autophagy functions together with apoptosis to determine the overall fate of the cell. The cross talk between this active self-destruction process and apoptosis is quite complex and contradictory as well, but it is unquestionably decisive for cell survival or cell death. Autophagy can promote tumor suppression but also tumor growth by inducing cancer-cell development and proliferation. In this review, we will discuss how autophagy reprograms tumor cells in the context of tumor hypoxic stress. We will illustrate how autophagy acts as both a suppressor and a driver of tumorigenesis through tuning survival in a context dependent manner. We also shed light on the relationship between autophagy and immune response in this complex regulation. A better understanding of the autophagy mechanisms and pathways will undoubtedly ameliorate the design of therapeutics aimed at targeting autophagy for future cancer immunotherapies.

Cloning of rabbit prolactin cDNA and prolactin gene expression in the rabbit mammary gland

1996 ◽  
Vol 16 (1) ◽  
pp. 27-37 ◽  
Author(s):  
L Gabou ◽  
M Boisnard ◽  
I Gourdou ◽  
H Jammes ◽  
J-P Dulor ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Amino Acid ◽  
Untranslated Regions ◽  
Pcr Analysis ◽  
Cdna Clones ◽  
Rt Pcr ◽  
Prolactin Gene ◽  
New Zealand White Rabbits ◽  
Rna Probe

ABSTRACT cDNA clones coding for rabbit prolactin were isolated from a pituitary library using a rat prolactin RNA probe. One cDNA contained 873 bases including the entire coding sequence of rabbit prolactin, its signal peptide and the 5′ and 3′ untranslated regions of 44 and 145 nucleotides respectively. The deduced amino acid sequence of the cloned prolactin cDNA presented a 93–78% identity with mink, porcine and human prolactins. The prolactin gene transcription was investigated by RT-PCR analysis in several organs of midlactating New Zealand White rabbits. The ectopic transcription of the prolactin gene was examined in more detail in the mammary gland. A strong PCR signal was detected in the mammary gland of virgin does and was also observed during pregnancy and at the beginning of lactation. This PCR signal was very weak in mid-lactating and absent in post-weaning mammary gland.

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