FOXO transcription factors are required for normal somatotrope function and growth

Endocrinology ◽  
2021 ◽  
Author(s):  
Caitlin E Stallings ◽  
Jyoti Kapali ◽  
Brian W Evans ◽  
Stacey R McGee ◽  
Buffy S Ellsworth
Keyword(s):  
Growth Hormone ◽  
Transcription Factors ◽  
Pituitary Gland ◽  
Molecular Mechanisms ◽  
Pituitary Growth Hormone ◽  
Related Family ◽  
Foxo Transcription Factors ◽  
Gland Function ◽  
And Function ◽  
Free Serum

Abstract Understanding the molecular mechanisms underlying pituitary organogenesis and function is essential for improving therapeutics and molecular diagnoses for hypopituitarism. We previously found that deletion of the forkhead factor, Foxo1, in the pituitary gland early in development delays somatotrope differentiation. While these mice grow normally, they have reduced growth hormone expression and free serum IGF1 levels, suggesting a defect in somatotrope function. FOXO factors show functional redundancy in other tissues, so we deleted both Foxo1 and its closely related family member, Foxo3, from the primordial pituitary. We find that this results in a significant reduction in growth. Consistent with this, male and female mice in which both genes have been deleted in the pituitary gland (dKO) exhibit reduced pituitary growth hormone expression and serum IGF1 levels. Expression of the somatotrope differentiation factor, Neurod4, is reduced in these mice. This suggests a mechanism underlying proper somatotrope function is the regulation of Neurod4 expression by FOXO factors. Additionally, dKO mice have reduced Lhb expression and females also have reduced Fshb and Prl expression. These studies reveal FOXO transcription factors as important regulators of pituitary gland function.

Human Pituitary Growth Hormone, by Allen W. Root, M.D. Springfield, Illinois: Charles C Thomas, 1972, 259 pp. $10.50

PEDIATRICS ◽  
1973 ◽  
Vol 52 (1) ◽  
pp. 158-159
Author(s):  
Selna L. Kaplan
Keyword(s):  
Growth Hormone ◽  
Pituitary Gland ◽  
Control Mechanisms ◽  
Human Pituitary ◽  
Comprehensive Review ◽  
Pituitary Growth Hormone ◽  
Biochemical Effects ◽  
Clinical Syndromes

This book, divided into four sections, provides a comprehensive review of the biochemical effects of growth hormone as well as the clinical syndromes associated with abnormalities of its secretion and metabolism. The book opens with a historical résumé of the "discovery" of this hormone, identification of its varied biologic actions, and isolation from the pituitary gland. The second part discusses the development of radioimmunoassay for measurement of growth hormone by Roth and associates and the subsequent surge in studies of the control mechanisms for the secretion of growth hormone.

scholarly journals Foxo Transcription Factors Control Regulatory T Cell Development and Function

Immunity ◽  
2011 ◽  
Vol 34 (1) ◽  
pp. 135
Author(s):  
Yann M. Kerdiles ◽  
Erica L. Stone ◽  
Daniel R. Beisner ◽  
Maureen A. McGargill ◽  
Irene L. Ch'en ◽  
...  
Keyword(s):  
Transcription Factors ◽  
T Cell ◽  
Regulatory T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Foxo Transcription Factors ◽  
And Function

scholarly journals Foxo Transcription Factors Control Regulatory T Cell Development and Function

Immunity ◽  
2010 ◽  
Vol 33 (6) ◽  
pp. 890-904 ◽  
Author(s):  
Yann M. Kerdiles ◽  
Erica L. Stone ◽  
Daniel L. Beisner ◽  
Maureen A. McGargill ◽  
Irene L. Ch'en ◽  
...  
Keyword(s):  
Transcription Factors ◽  
T Cell ◽  
Regulatory T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Foxo Transcription Factors ◽  
And Function

scholarly journals Does Calorie Restriction Modulate Inflammaging via FoxO Transcription Factors?

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1959
Author(s):  
Sang-Eun Kim ◽  
Ryoichi Mori ◽  
Isao Shimokawa
Keyword(s):  
Transcription Factors ◽  
Calorie Restriction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Functional Decline ◽  
Cell Lineage ◽  
Myeloid Cell ◽  
The Body ◽  
Pyrin Domain ◽  
Foxo Transcription Factors

Calorie restriction (CR) has been shown to extend lifespan and retard aging-related functional decline in animals. Previously, we found that the anti-neoplastic and lifespan-extending effects of CR in mice are regulated by forkhead box O transcription factors (FoxO1 and FoxO3), located downstream of growth hormone (GH)–insulin-like growth factor (IGF)-1 signaling, in an isoform-specific manner. Inflammaging is a term coined to represent that persistent low-level of inflammation underlies the progression of aging and related diseases. Attenuation of inflammaging in the body may underlie the effects of CR. Recent studies have also identified cellular senescence and activation of the nucleotide-binding domain, leucine-rich-containing family, pyrin-domain-containing-3 (NLRP3) inflammasome as causative factors of inflammaging. In this paper, we reviewed the current knowledge of the molecular mechanisms linking the effects of CR with the formation of inflammasomes, particularly focusing on possible relations with FoxO3. Inflammation in the brain that affects adult neurogenesis and lifespan was also reviewed as evidence of inflammaging. A recent progress of microRNA research was described as regulatory circuits of initiation and propagation of inflammaging. Finally, we briefly introduced our preliminary results obtained from the mouse models, in which Foxo1 and Foxo3 genes were conditionally knocked out in the myeloid cell lineage.

scholarly journals MicroRNAs in the Neural Retina

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Kalina Andreeva ◽  
Nigel G. F. Cooper
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Neural Retina ◽  
Posttranscriptional Gene Regulation ◽  
Long Time ◽  
Gene Transcripts ◽  
The Central Nervous System ◽  
And Function ◽  
And Control

The health and function of the visual system rely on a collaborative interaction between diverse classes of molecular regulators. One of these classes consists of transcription factors, which are known to bind to DNA and control the transcription activities of their target genes. For a long time, it was thought that the transcription factors were the only regulators of gene expression. More recently, however, a novel class of regulators emerged. This class consists of a large number of small noncoding endogenous RNAs, namely, miRNAs. The miRNAs compose an essential component of posttranscriptional gene regulation, since they ultimately control the fate of gene transcripts. The retina, as a part of the central nervous system, is a well-established model for unraveling the molecular mechanisms underlying neuronal and glial functions. Numerous recent efforts have been made towards identification of miRNAs and their inferred roles in the visual pathway. In this review, we summarize the current state of our knowledge regarding the expression and function of miRNA in the neural retina and we discuss their potential uses as biomarkers for some retinal disorders.

scholarly journals Experimental modification of rat pituitary growth hormone cell function during and after spaceflight

1996 ◽  
Vol 80 (3) ◽  
pp. 955-970 ◽  
Author(s):  
W. C. Hymer ◽  
R. E. Grindeland ◽  
T. Salada ◽  
P. Nye ◽  
E. J. Grossman ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cell Function ◽  
Cell Types ◽  
Secretory Cells ◽  
Mixed Cell ◽  
Pituitary Growth Hormone ◽  
Gh Cells ◽  
Growth Hormone Cell ◽  
And Function

Space-flown rats show a number of flight-induced changes in the structure and function of pituitary growth hormone (GH) cells after in vitro postflight testing (W. C. Hymen, R. E. Grindeland, I. Krasnov, I, Victorov, K. Motter, P. Mukherjee, K. Shellenberger, and M. Vasques. J. Appl. Physiol. 73, Suppl.: 151S-157S, 1992). To evaluate the possible effects of microgravity on growth hormone (GH) cells themselves, freshly dispersed rat anterior pituitary gland cells were seeded into vials containing serum +/- microM hydrocortisone (HC) before flight. Five different cell preparations were used: the entire mixed-cell population of various hormone-producing cell types, cells of density < 1.071 g/cm3 (band 1), cells of density > 1.071 g/cm3 (band 2), and cells prepared from either the dorsal or ventral part of the gland. Relative to ground control samples, bioactive GH released from dense cells during flight was reduced in HC-free medium but was increased in HC-containing medium. Band 1 and mixed cells usually showed opposite HC-dependent responses. Release of bioactive GH from ventral flight cells was lower; postflight responses to GH-releasing hormone challenge were reduced, and the cytoplasmic area occupied by GH in the dense cells was greater. Collectively, the data show that the chemistry and cellular makeup of the culture system modifies the response of GH cells to microgravity. As such, these cells offer a system to identify gravisensing mechanisms in secretory cells in future microgravity research.

scholarly journals The emerging role of FOXO transcription factors in pancreatic β cells

2007 ◽  
Vol 193 (2) ◽  
pp. 195-207 ◽  
Author(s):  
Dominique A Glauser ◽  
Werner Schlegel
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Cell Mass ◽  
Endocrine Function ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Foxo Transcription Factors

FOXO transcription factors critically control fundamental cellular processes, including metabolism, cell differentiation, cell cycle arrest, DNA repair, and other reactions to cellular stress. FOXO factors sense the balance between stimuli promoting growth and differentiation versus stress stimuli signaling damage. Integrated through the FOXO system, these divergent stimuli decide on cell fate, a choice between proliferation, differentiation, or apoptosis. In pancreatic β cells, most recent evidence highlights complex FOXO-dependent responses to glucose, insulin, or other growth factors, which include regulatory feedback. In the short term, FOXO-dependent mechanisms help β cells to accomplish their endocrine function, and may increase their resistance to oxidative stress due to transient hyperglycemia. In the long term, FOXO-dependent responses lead to the adaptation of β cell mass, conditioning the future ability of the organism to produce insulin and cope with changes in fuel abundance. FOXO emerges as a key factor for the maintenance of a functional endocrine pancreas and represents an interesting element in the development of therapeutic approaches to treat diabetes. This review on the role of FOXO transcription factors in pancreatic β cells has three parts. In Part I, FOXO transcription factors will be presented in general: structure, molecular mechanisms of regulation, cellular functions, and physiological roles. Part II will focus on specific data about FOXO factors in pancreatic β cells. Lastly in Part III, it will be attempted to combine general and β cell-specific knowledge with the aim to envisage globally the role of FOXO factors in β cell-linked physiology and disease.

scholarly journals The Enigmatic HOX Genes: Can We Crack Their Code?

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 323 ◽  
Author(s):  
Zhifei Luo ◽  
Suhn Rhie ◽  
Peggy Farnham
Keyword(s):  
Transcription Factors ◽  
Embryonic Development ◽  
Molecular Mechanisms ◽  
Hox Genes ◽  
Homeobox Genes ◽  
Large Family ◽  
Cell Types ◽  
Interacting Protein ◽  
Developmental Problems ◽  
And Function

Homeobox genes (HOX) are a large family of transcription factors that direct the formation of many body structures during early embryonic development. There are 39 genes in the subgroup of homeobox genes that constitute the human HOX gene family. Correct embryonic development of flies and vertebrates is, in part, mediated by the unique and highly regulated expression pattern of the HOX genes. Disruptions in these fine-tuned regulatory mechanisms can lead to developmental problems and to human diseases such as cancer. Unfortunately, the molecular mechanisms of action of the HOX family of transcription factors are severely under-studied, likely due to idiosyncratic details of their structure, expression, and function. We suggest that a concerted and collaborative effort to identify interacting protein partners, produce genome-wide binding profiles, and develop HOX network inhibitors in a variety of human cell types will lead to a deeper understanding of human development and disease. Within, we review the technological challenges and possible approaches needed to achieve this goal.

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