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https://www.readbyqxmd.com/read/28425851/altered-structure-and-function-of-adipose-tissue-in-long-lived-mice-with-growth-hormone-related-mutations
#1
Justin Darcy, Samuel McFadden, Andrzej Bartke
A major focus of biogerontology is elucidating the role(s) of the endocrine system in aging and the accumulation of age-related diseases. Endocrine control of mammalian longevity was first reported in Ames dwarf (Prop1(df)) mice, which are long-lived due to a recessive Prop1 loss-of-function mutation resulting in deficiency of growth hormone (GH), thyroid-stimulating hormone, and prolactin. Following this report, several other GH-related mutants with altered longevity have been described including long-lived Snell dwarf and growth hormone receptor knockout mice, and short-lived GH overexpressing transgenic mice...
March 21, 2017: Adipocyte
https://www.readbyqxmd.com/read/28356564/combined-pituitary-hormone-deficiency-due-to-gross-deletions-in-the-pou1f1-pit-1-and-prop1-genes
#2
Eleonore Bertko, Jürgen Klammt, Petra Dusatkova, Mithat Bahceci, Nazli Gonc, Louise Ten Have, Nurgun Kandemir, Georg Mansmann, Barbora Obermannova, Wilma Oostdijk, Heike Pfäffle, Denise Rockstroh-Lippold, Marina Schlicke, Alpaslan Kemal Tuzcu, Roland Pfäffle
Pituitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined pituitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure. We analyzed 70 CPHD patients from 64 families. Deletions were found in three Turkish families and one family from northern Iraq. In one family we identified a 4.96 kb deletion that comprises the first two exons of POU1F1...
March 30, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28351423/epigenetic-aging-signatures-in-mice-livers-are-slowed-by-dwarfism-calorie-restriction-and-rapamycin-treatment
#3
Tina Wang, Brian Tsui, Jason F Kreisberg, Neil A Robertson, Andrew M Gross, Michael Ku Yu, Hannah Carter, Holly M Brown-Borg, Peter D Adams, Trey Ideker
BACKGROUND: Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. RESULTS: We first examined whether mice and humans experience similar patterns of change in the methylome with age...
March 28, 2017: Genome Biology
https://www.readbyqxmd.com/read/28351383/diverse-interventions-that-extend-mouse-lifespan-suppress-shared-age-associated-epigenetic-changes-at-critical-gene-regulatory-regions
#4
John J Cole, Neil A Robertson, Mohammed Iqbal Rather, John P Thomson, Tony McBryan, Duncan Sproul, Tina Wang, Claire Brock, William Clark, Trey Ideker, Richard R Meehan, Richard A Miller, Holly M Brown-Borg, Peter D Adams
BACKGROUND: Age-associated epigenetic changes are implicated in aging. Notably, age-associated DNA methylation changes comprise a so-called aging "clock", a robust biomarker of aging. However, while genetic, dietary and drug interventions can extend lifespan, their impact on the epigenome is uncharacterised. To fill this knowledge gap, we defined age-associated DNA methylation changes at the whole-genome, single-nucleotide level in mouse liver and tested the impact of longevity-promoting interventions, specifically the Ames dwarf Prop1 (df/df) mutation, calorie restriction and rapamycin...
March 28, 2017: Genome Biology
https://www.readbyqxmd.com/read/28332357/rare-frequency-of-mutations-in-pituitary-transcription-factor-genes-in-combined-pituitary-hormone-or-isolated-growth-hormone-deficiencies-in-korea
#5
Jin Ho Choi, Chang Woo Jung, Eungu Kang, Yoon Myung Kim, Sun Hee Heo, Beom Hee Lee, Gu Hwan Kim, Han Wook Yoo
PURPOSE: Congenital hypopituitarism is caused by mutations in pituitary transcription factors involved in the development of the hypothalamic-pituitary axis. Mutation frequencies of genes involved in congenital hypopituitarism are extremely low and vary substantially between ethnicities. This study was undertaken to compare the clinical, endocrinological, and radiological features of patients with an isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD)...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/27974186/classical-and-non-classical-causes-of-gh-deficiency-in-the-paediatric-age
#6
REVIEW
Natascia Di Iorgi, Giovanni Morana, Anna Elsa Maria Allegri, Flavia Napoli, Roberto Gastaldi, Annalisa Calcagno, Giuseppa Patti, Sandro Loche, Mohamad Maghnie
Growth hormone deficiency (GHD) may result from a failure of hypothalamic GHRH production or release, from congenital disorders of pituitary development, or from central nervous system insults including tumors, surgery, trauma, radiation or infiltration from inflammatory diseases. Idiopathic, isolated GHD is the most common sporadic form of hypopituitarism. GHD may also occur in combination with other pituitary hormone deficiencies, and is often referred to as hypopituitarism, combined pituitary hormone deficiency (CPHD), multiple pituitary hormone deficiency (MPHD) or panhypopituitarism...
December 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/27974184/genetic-causes-of-isolated-and-combined-pituitary-hormone-deficiency
#7
REVIEW
Mara Giordano
Research over the last 20 years has led to the elucidation of the genetic aetiologies of Isolated Growth Hormone Deficiency (IGHD) and Combined Pituitary Hormone Deficiency (CPHD). The pituitary plays a central role in growth regulation, coordinating the multitude of central and peripheral signals to maintain the body's internal balance. Naturally occurring mutation in humans and in mice have demonstrated a role for several factors in the aetiology of IGHD/CPHD. Mutations in the GH1 and GHRHR genes shed light on the phenotype and pathogenesis of IGHD whereas mutations in transcription factors such as HESX1, PROP1, POU1F1, LHX3, LHX4, GLI2 and SOX3 contributed to the understanding of CPHD...
December 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/27917547/pituitary-stalk-interruption-syndrome-from-clinical-findings-to-pathogenesis
#8
REVIEW
C-Z Wang, L-L Guo, B-Y Han, X Su, Q-H Guo, Y-M Mu
Pituitary stalk interruption syndrome (PSIS) is a rare congenital defect manifesting with varying degrees of pituitary hormone deficiency. The signs and symptoms of PSIS during the neonatal period and infancy are often overlooked and therefore diagnosis is delayed. The typical manifestations of PSIS can be detected by magnetic resonance imaging. Several genes in the Wnt, Notch and Shh signalling pathways related to hypothalamic-pituitary development, such as PIT1, PROP1, LHX3/LHX4, PROKR2, OTX2, TGIF and HESX1, have been found to be associated with PSIS...
January 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/27773885/involvement-of-dna-methylation-in-regulating-rat-prop1-gene-expression-during-pituitary-organogenesis
#9
Hiroto Nishihara, Saishu Yoshida, Naoko Kanno, Naoto Nishimura, Hiroki Ueharu, Jun Ohgane, Takako Kato, Yukio Kato
PROP1 is a pituitary specific transcription factor that plays a crucial role in pituitary organogenesis. The Prop1 shows varied expression patterns that promptly emerge and then fade during the early embryonic period. However, the regulatory mechanisms governing Prop1 expression remain unclear. Here, we investigated whether Prop1 was under epigenetic regulation by DNA methylation. Bisulfite sequencing was performed on DNA obtained from the pituitary glands and livers of rats on embryonic days (E) 13.5 and E14...
February 16, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/27756091/identification-of-novel-prop1-and-pou1f1-mutations-in-patients-with-combined-pituitary-hormone-deficiency
#10
S Birla, R Khadgawat, V P Jyotsna, V Jain, M K Garg, A S Bhalla, A Sharma
Growth hormone deficiency (GHD) results from variations affecting the production and release of growth hormone (GH) and is of 2 types: isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD). IGHD results from mutations in GH1 and GHRHR while CPHD is associated with defects in transcription factor genes PROP1, POU1F1, and HESX1. The present study reports on screening of POU1F1, PROP1, and HESX1 in CPHD patients and the novel variations identified. Fifty-one CPHD patients from 49 unrelated families clinically diagnosed on the basis of biochemical and imaging investigations along with 100 controls were enrolled...
December 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/27740871/brown-adipose-tissue-function-is-enhanced-in-long-lived-male-ames-dwarf-mice
#11
Justin Darcy, Samuel McFadden, Yimin Fang, Joshua A Huber, Chi Zhang, Liou Y Sun, Andrzej Bartke
Ames dwarf mice (Prop1(df/df)) are long-lived due to a loss of function mutation, resulting in deficiency of GH, TSH, and prolactin. Along with a marked extension of longevity, Ames dwarf mice have improved energy metabolism as measured by an increase in their oxygen consumption and heat production, as well as a decrease in their respiratory quotient. Along with alterations in energy metabolism, Ames dwarf mice have a lower core body temperature. Moreover, Ames dwarf mice have functionally altered epididymal white adipose tissue (WAT) that improves, rather than impairs, their insulin sensitivity due to a shift from pro- to anti-inflammatory cytokine secretion...
December 2016: Endocrinology
https://www.readbyqxmd.com/read/27685990/cocaine-and-amphetamine-regulated-transcript-cart-peptide-is-expressed-in-precursor-cells-and-somatotropes-of-the-mouse-pituitary-gland
#12
Amanda H Mortensen, Sally A Camper
Cocaine-and Amphetamine Regulated Transcript (CART) peptide is expressed in the brain, endocrine and neuroendocrine systems and secreted into the serum. It is thought to play a role in regulation of hypothalamic pituitary functions. Here we report a spatial and temporal analysis of Cart expression in the pituitaries of adult and developing normal and mutant mice with hypopituitarism. We found that Prop1 is not necessary for initiation of Cart expression in the fetal pituitary at e14.5, but it is required indirectly for maintenance of Cart expression in the postnatal anterior pituitary gland...
2016: PloS One
https://www.readbyqxmd.com/read/27650955/regulation-of-pituitary-stem-cells-by-epithelial-to-mesenchymal-transition-events-and-signaling-pathways
#13
Leonard Y M Cheung, Shannon W Davis, Michelle L Brinkmeier, Sally A Camper, María Inés Pérez-Millán
The anterior pituitary gland is comprised of specialized cell-types that produce and secrete polypeptide hormones in response to hypothalamic input and feedback from target organs. These specialized cells arise from stem cells that express SOX2 and the pituitary transcription factor PROP1, which is necessary to establish the stem cell pool and promote an epithelial to mesenchymal-like transition, releasing progenitors from the niche. The adult anterior pituitary responds to physiological challenge by mobilizing the SOX2-expressing progenitor pool and producing additional hormone-producing cells...
April 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27596959/isolation-of-adult-pituitary-stem-progenitor-cell-clusters-located-in-the-parenchyma-of-the-rat-anterior-lobe
#14
Saishu Yoshida, Naoto Nishimura, Hiroki Ueharu, Naoko Kanno, Masashi Higuchi, Kotaro Horiguchi, Takako Kato, Yukio Kato
Recent studies have demonstrated that Sox2-expressing stem/progenitor cells play roles in the pituitary cell turnover. Two types of niches have been proposed for stem/progenitor cells, the marginal cell layer (MCL) and the dense cell clusters in the parenchyma. Among them, the appearance of the parenchymal-niche only after birth indicates that this niche is involved in the cell turnover required for the postnatal pituitary. However, little is known about the roles of the parenchymal-niche and its regulation...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27564454/identification-of-a-novel-progenitor-cell-marker-grainyhead-like-2-in-the-developing-pituitary
#15
Whitney Edwards, Leah B Nantie, Lori T Raetzman
BACKGROUND: Pituitary stem/progenitor cells give rise to all of the endocrine cell types within the pituitary gland and are necessary for both development and gland homeostasis. Recent studies have identified several key factors that characterize the progenitor cell population. However, little is known about the factors that regulate progenitor cell differentiation and maintenance. Therefore, it is crucial to identify novel factors that help elucidate mechanisms of progenitor cell function in the developing pituitary...
November 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/27487097/long-term-outcomes-genetics-and-pituitary-morphology-in-patients-with-isolated-growth-hormone-deficiency-and-multiple-pituitary-hormone-deficiencies-a-single-centre-experience-of-four-decades-of-growth-hormone-replacement
#16
Julia Rohayem, Hendrik Drechsel, Bettina Tittel, Gabriele Hahn, Roland Pfaeffle, Angela Huebner
BACKGROUND: Growth hormone (GH) has been used to treat children with GH deficiency (GHD) since 1966. AIMS: Using a combined retrospective and cross-sectional approach, we explored the long-term outcomes of patients with GHD, analysed factors influencing therapeutic response, determined persistence into adulthood, investigated pituitary morphology, and screened for mutations in causative genes. METHODS: The files of 96 GH-deficient children were reviewed...
2016: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/27351100/prop1-triggers-epithelial-mesenchymal-transition-like-process-in-pituitary-stem-cells
#17
María Inés Pérez Millán, Michelle L Brinkmeier, Amanda H Mortensen, Sally A Camper
Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the repression and activation of the pituitary transcription factor genes Hesx1 and Pou1f1, respectively. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome-wide analysis of PROP1 DNA binding and effects on gene expression in mutant mice, mouse isolated stem cells and engineered mouse cell lines...
2016: ELife
https://www.readbyqxmd.com/read/27226307/growth-hormone-is-permissive-for-neoplastic-colon-growth
#18
Vera Chesnokova, Svetlana Zonis, Cuiqi Zhou, Maria Victoria Recouvreux, Anat Ben-Shlomo, Takako Araki, Robert Barrett, Michael Workman, Kolja Wawrowsky, Vladimir A Ljubimov, Magdalena Uhart, Shlomo Melmed
Growth hormone (GH) excess in acromegaly is associated with increased precancerous colon polyps and soft tissue adenomas, whereas short-stature humans harboring an inactivating GH receptor mutation do not develop cancer. We show that locally expressed colon GH is abundant in conditions predisposing to colon cancer and in colon adenocarcinoma-associated stromal fibroblasts. Administration of a GH receptor (GHR) blocker in acromegaly patients induced colon p53 and adenomatous polyposis coli (APC), reversing progrowth GH signals...
June 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27190246/original-research-metabolic-alterations-from-early-life-thyroxine-replacement-therapy-in-male-ames-dwarf-mice-are-transient
#19
Justin Darcy, Yimin Fang, Cristal M Hill, Sam McFadden, Liou Y Sun, Andrzej Bartke
Ames dwarf mice are exceptionally long-lived due to a Prop1 loss of function mutation resulting in deficiency of growth hormone, thyroid-stimulating hormone and prolactin. Deficiency in thyroid-stimulating hormone and growth hormone leads to greatly reduced levels of circulating thyroid hormones and insulin-like growth factor 1, as well as a reduction in insulin secretion. Early life growth hormone replacement therapy in Ames dwarf mice significantly shortens their longevity, while early life thyroxine (T4) replacement therapy does not...
October 2016: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27114065/identification-of-novel-ghrhr-and-gh1-mutations-in-patients-with-isolated-growth-hormone-deficiency
#20
Shweta Birla, Rajesh Khadgawat, Viveka P Jyotsna, Vandana Jain, M K Garg, Ashu Seith Bhalla, Arundhati Sharma
OBJECTIVE: Human growth is an elementary process which starts at conception and continues through different stages of development under the influence of growth hormone (GH) secreted by the anterior pituitary gland. Variation affecting the production, release and functional activity of GH leads to growth hormone deficiency (GHD), which is of two types: isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD). IGHD may result from mutations in GH1 and GHRHR while CPHD is associated with defects in transcription factor genes PROP1, POU1F1 and HESX1...
August 2016: Growth Hormone & IGF Research
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