{"title":"Time course and reaction types of serum IGF-1 and its relationship to BMI and leptin regarding inpatients with anorexia nervosa","authors":"Christiane Hellwig-Walter , Maik Brune , Dieter Schellberg , Magdalena Buckert , Daniela Wesche , Ulrich Cuntz , Hans-Christoph Friederich , Beate Wild","doi":"10.1016/j.ghir.2022.101470","DOIUrl":"10.1016/j.ghir.2022.101470","url":null,"abstract":"<div><h3>Objective</h3><p>Anorexia nervosa (AN) is a severe mental disorder that is characterized by restriction of energy intake, low weight, and endocrine abnormalities. One of the known endocrine changes in relation to underweight is in the GH/IGF-I axis. The aim of the study was (a) to investigate longitudinal characteristics of the IGF-I-change during therapy and weight gain in adult AN, (b) to determine relationships between IGF-I and leptin, (c) to characterize patients with weak and pronounced hormonal reactions to underweight.</p></div><div><h3>Design</h3><p>Data was assessed from 19 AN patients. Over the first two months, serum IGF-I concentrations were assessed on a weekly basis; thereafter on a monthly basis. The trend of IGF-I values over time was analyzed using individual growth models.</p></div><div><h3>Results</h3><p>In total, <em>n</em> = 177 IGF-I measurements were analyzed. IGF-I increased significantly dependent on BMI (slope = 20.81, <em>p</em> < 0.001), not modulated by duration of disease. The increase in IGF-I was significantly related to the increase in leptin concentrations over time (slope = 15.57, <em>p</em> < 0.001). Patients with a weaker hormonal reaction to underweight were significantly older compared to patients with a pronounced hormonal reaction (t(17) = 3.07, <em>p</em> = 0.007).</p></div><div><h3>Conclusions</h3><p>During treatment, IGF-I change is clearly related to BMI as well as to leptin. Age appears to be associated with the IGF-I response to underweight.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"64 ","pages":"Article 101470"},"PeriodicalIF":1.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90100572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carolina Peixe , Miriam Sánchez-García , Ashley B. Grossman , Márta Korbonits , Pedro Marques
{"title":"Biochemical discrepancies in the evaluation of the somatotroph axis: Elevated GH or IGF-1 levels do not always diagnose acromegaly","authors":"Carolina Peixe , Miriam Sánchez-García , Ashley B. Grossman , Márta Korbonits , Pedro Marques","doi":"10.1016/j.ghir.2022.101467","DOIUrl":"10.1016/j.ghir.2022.101467","url":null,"abstract":"<div><p><span>The most frequent diagnosis underlying the finding of an elevated growth hormone (GH) and insulin-like growth factor-1 (IGF-1) is acromegaly due to a GH-secreting pituitary tumour. However, GH and IGF-1 levels can be discordant </span>in patients with acromegaly due to early or partially treated disease, or there might be another cause of high GH or high IGF-1 unrelated to acromegaly, such as pre-analytical and technical pitfalls, physiological circumstances and pathological conditions. High GH and normal or low serum IGF-1, or alternatively, normal GH with elevated serum IGF-1, should be carefully assessed to avoid misinterpreting the activity of acromegaly or misdiagnosing a patient with acromegaly. We summarise here these biochemical discrepancies in the evaluation of the somatotroph axis.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"64 ","pages":"Article 101467"},"PeriodicalIF":1.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77397512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yogesh C. Bangar, Ankit Magotra, A.S. Yadav, C.S. Patil
{"title":"Meta-analysis of MspI derived variants of growth hormone gene associated with milk yield in dairy cattle","authors":"Yogesh C. Bangar, Ankit Magotra, A.S. Yadav, C.S. Patil","doi":"10.1016/j.ghir.2022.101459","DOIUrl":"10.1016/j.ghir.2022.101459","url":null,"abstract":"<div><h3>Objective</h3><p>The present work aimed to obtain common effect sizes for the gene frequency and association of <em>Msp</em>I derived variants of growth hormone (GH) gene with milk yield in dairy cows.</p></div><div><h3>Methods</h3><p><span>We performed a systematic review and meta-analysis of 35 published studies identified in literature search from 2000 to 2020 (</span><em>n</em> = 4164). These studies were specific to fragment size (329) for genotypes viz.<em>,</em> CC (224, 105 bp), CD (329, 224, 105 bp) and DD (329 bp). Pooled standard mean differences (SMDs) as effect sizes between allele pairs were derived using different genetic models. The heterogeneity between effects sizes across studies was estimated using I<sup>2</sup> Index (%).</p></div><div><h3>Results</h3><p>The common effect size for gene frequency of allele C (224, 105 bp) was significantly (<em>P</em> < 0.05) higher in 2881 <span><em>Bos taurus</em></span>/cross cows (0.82; 95% CI: 0.74, 0.89; I<sup>2</sup> = 97.81%) than 1283 <span><em>Bos indicus</em></span> cows (0.15; 95% CI: 0.12, 0.18; I<sup>2</sup> = 71.90%), with overall gene frequency was 0.33 (95% CI: 0.21, 0.46; I<sup>2</sup> = 99.29%). Additive (CC vs. DD) and dominant (CC + CD vs. DD) did not revealed significant (<em>P</em> > 0.05) association with milk yield. However, completely over dominant (CC + DD vs. CD) and recessive (CC vs. CD + DD) models showed significant (<em>P</em><span> < 0.05) and positive SMDs with milk yield specially at early lactations. There was no evidence of heterogeneity (I</span><sup>2</sup> = 0.00%) between SMDs across studies.</p></div><div><h3>Conclusions</h3><p>This meta-analysis suggested potential association of C allele for enhancing milk production of dairy cows.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"63 ","pages":"Article 101459"},"PeriodicalIF":1.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84620827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of growth hormone for fertility in women with hypopituitarism","authors":"Julie Chen , Laurence Katznelson","doi":"10.1016/j.ghir.2022.101458","DOIUrl":"10.1016/j.ghir.2022.101458","url":null,"abstract":"<div><p><span><span>Growth hormone (GH) is an important regulator of the female reproductive system. In vitro and non-human in vivo studies demonstrate a role of GH in </span>steroidogenesis, </span>folliculogenesis<span><span>, and post-fertilization development. Given its ability to modulate the reproductive system and potentiate the effects of gonadotropins<span>, a beneficial role of GH replacement therapy to optimize fertility has been suggested. Women with hypopituitarism have lower pregnancy and live birth rates. Limited data suggest a role of GH in enhancing fertility management in women with hypopituitarism. GH replacement therapy may be especially relevant in women with hypopituitarism as well as in women considered poor ovarian responders and require </span></span>assisted reproductive techniques.</span></p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"63 ","pages":"Article 101458"},"PeriodicalIF":1.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78765154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jithine Jayakumar Rajeswari , Emilio J. Vélez , Suraj Unniappan
{"title":"Liver and muscle-specific effects of phoenixin-20 on the insulin-like growth factor system mRNAs in zebrafish","authors":"Jithine Jayakumar Rajeswari , Emilio J. Vélez , Suraj Unniappan","doi":"10.1016/j.ghir.2022.101456","DOIUrl":"10.1016/j.ghir.2022.101456","url":null,"abstract":"<div><h3>Objective</h3><p>Phoenixin-20 (Pnx-20) is a bioactive peptide with endocrine-like actions in vertebrates. Recent studies suggest Pnx-20 promotes growth hormone/insulin-like growth factors (Gh/Igf) axis, an important endocrine regulator of growth in mammals and fish.</p></div><div><h3>Design</h3><p>In this research, we determined whether Pnx-20 affects the different members of the Igf family, its binding proteins and receptors (Igf-system) in zebrafish liver and muscle.</p></div><div><h3>Results</h3><p><em>In vivo</em> administration of Pnx-20 downregulated <em>igfs</em>, <em>igf</em> receptor<em>s</em> (<em>igfrs</em>) and <em>igf</em> binding protein (<em>igfbp</em>) 5 mRNA expression in the liver of male and female zebrafish at both 1 and 6 h post-intraperitoneal (IP) injection. Interestingly, this effect occurred at a relatively earlier timepoint in female zebrafish suggesting sex-specific differences in Pnx-20 action. Besides, either 6 or 24 h <em>in vitro</em> incubations with Pnx-20 downregulated the expression of all <em>igfs</em>, <em>igf</em>rs and <span><em>igfbp5</em></span> mRNAs (except <em>igf2a</em>) analyzed in a zebrafish liver cell (ZFL) line. Moreover, siRNA-mediated knockdown of Pnx-20 upregulated all Igf-system mRNAs analyzed in ZFL cells. Together, these results (both <em>in vivo</em> and <em>in vitro</em>) revealed a general suppressive action for both endogenous and exogenous Pnx-20 on the hepatic Igf-system of zebrafish. In contrast, a general sex-specific upregulation of the Igf-system mRNAs analyzed was found in the muscle of Pnx-20 injected fish. Future research should explore the sex- and time-differences observed in the present study.</p></div><div><h3>Conclusions</h3><p>Collectively, this research shows that Pnx-20 is a tissue-specific regulator of the liver (suppressor) and muscle (stimulant) Igf signaling in both male and female zebrafish.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"63 ","pages":"Article 101456"},"PeriodicalIF":1.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77836395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Maddalena Sirufo , Lina Maria Magnanimi , Lia Ginaldi , Massimo De Martinis
{"title":"The true story of the “strong and gentle” Acciano's Giant","authors":"Maria Maddalena Sirufo , Lina Maria Magnanimi , Lia Ginaldi , Massimo De Martinis","doi":"10.1016/j.ghir.2022.101457","DOIUrl":"10.1016/j.ghir.2022.101457","url":null,"abstract":"<div><p><span>This is the story of a giant who lived in Abruzzo 200 years ago. He became a symbol for his people and a strong resilience generator. Gigantism, in the history of humanity has always attracted attention, albeit passing over the centuries from myth, from divinity to the freak phenomenon, the freak of nature that becomes a spectacle to show off. The attraction for understanding the pathophysiological mechanisms underlying gigantism developed by the end of 19th century. Increased levels of growth hormone (GH) or insulin-like </span>growth hormone 1 (IGF1) causes overgrowth in pituitary gigantism. The imposing size of the body, in our imagination, represents strength and health, reason why in our imagination it almost becomes a divine mythical image. The story of the Acciano's Giant represents a cultural heritage that passes from one generation to the next, that contributes in giving a sense of identity and continuity. It provides a link from past to present and to the future. Encourages a sense of identity and responsibility contributing to social cohesion, helping individuals to feel members of one community. A disease, represented by the Giant, has become a symbol capable of bringing the community together and giving it the strength to react to environment, nature and history. This is a lesson that teaches us the sense of community.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"63 ","pages":"Article 101457"},"PeriodicalIF":1.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40325446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hormonal, metabolic, and angiogenic responses to all-out sprint interval exercise under systemic hyperoxia","authors":"Michihiro Kon , Yoshiko Ebi , Kohei Nakagaki","doi":"10.1016/j.ghir.2022.101445","DOIUrl":"10.1016/j.ghir.2022.101445","url":null,"abstract":"<div><h3>Objective</h3><p>Hyperoxic gas inhalation during exercise may negatively affect all-out sprint interval exercise (SIE)-induced hormonal, metabolic, and angiogenic responses. We investigated the effects of acute all-out SIE under systemic hyperoxia on hormonal, metabolic, and angiogenic responses.</p></div><div><h3>Design</h3><p><span>This was a randomised-crossover trial. Ten healthy males (mean ± standard error of age = 23.1 ± 0.9 years; height = 171.0 ± 1.6 cm; body mass = 66.2 ± 2.0 kg; body mass index = 22.6 ± 0.5 kg/m</span><sup>2</sup>) completed the following two experimental regimens: 1) SIE under normoxia and 2) SIE under systemic hyperoxia (FiO<sub>2</sub><span> = 60%). The subjects performed four bouts of 30-s maximal cycling efforts with 4 min recovery between efforts. The circulating levels of hormonal (growth hormone, epinephrine, and norepinephrine), metabolic (glucose, free fatty acid, and lactate), and angiogenic (vascular endothelial growth factor, matrix metalloproteinase-2 and -9, and endostatin) markers were measured before and at 0 (immediately after the regimen), 30, and 120 min after both regimens.</span></p></div><div><h3>Results</h3><p>In response to both SIE regimens, the peak and mean power outputs gradually decreased over the intermittent exercise session compared with those in the first bout (p < 0.01) with no significant differences between the regimens. Both regimens significantly increased the circulating concentrations of all hormonal, metabolic, and angiogenic markers (p < 0.01). However, there were no significant differences in the levels of these markers in response to the two regimens at any time point (p > 0.05).</p></div><div><h3>Conclusion</h3><p>These findings suggest that acute systemic hyperoxia does not influence the hormonal, metabolic, and angiogenic responses to all-out SIE.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"63 ","pages":"Article 101445"},"PeriodicalIF":1.4,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39926431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qin Shen , Xia Wang , Haodi Bai , Xin Tan , Xing Liu
{"title":"Effects of high-dose all-trans retinoic acid on longitudinal bone growth of young rats","authors":"Qin Shen , Xia Wang , Haodi Bai , Xin Tan , Xing Liu","doi":"10.1016/j.ghir.2022.101446","DOIUrl":"10.1016/j.ghir.2022.101446","url":null,"abstract":"<div><h3>Objective</h3><p>The signaling axis consisting of GH-IGF1-IGFBP3 is the primary signal taht acts prepubertally to influence height development. Growth plate<span><span><span><span> thinning and even premature closure have been reported in children with tumors treated with retinoid chemotherapy, resulting in long </span>bone dysplasia. Growth failure may occur despite received GH </span>treatment<span>, but the reason is unknown. This study investigate the effect of high-dose all-trans retinoic acid (ATRA) on the development of long bones in growing </span></span>SD rats.</span></p></div><div><h3>Methods</h3><p>A total of 20 three-week-old male SD rats were randomly divided into a control group and an experimental group (<em>n</em><span> = 10). Rats were treated by gavage with or without high-dose ATRA for 10 days. The body weights of the rats were recorded daily. At the end of the experiment, we measured the length of nose-tail and tibia<span>, stained the tibia and liver for pathological tissue<span><span> and RT-PCR reaction, and measured the levels of serum GH, IGF1 and </span>IGFBP3, and so on.</span></span></span></p></div><div><h3>Results</h3><p>Compared with controls, experimental rats exhibited reduced body weight and shortened nasal-tail and radial tibial length. Cyp26b1 enzyme activity<span><span><span> in the liver was elevated, and histopathological staining revealed that the cartilaginous epiphyseal plate was narrowed, the medullary cavity of trabecular bone was sparse, the number of trabecular bones was decreased, trabecular separation was increased, bone marrow </span>mineralization was enhanced, osteoclastic activity was increased, and circulating GH-IGF1-IGFBP3 levels were decreased. However, RT-PCR reaction results of localized </span>proximal tibiae showed upregulation of IGF1 and downregulation of IGFBP3.</span></p></div><div><h3>Conclusions</h3><p>High-dose ATRA intake over a short period of time can reduce GH-IGF1-IGFBP3 levels, affect cartilage and bone homeostasis, and inhibit bone growth in developing animals.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"62 ","pages":"Article 101446"},"PeriodicalIF":1.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39911457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rafaela S. Girão , Manuel H. Aguiar-Oliveira , Bruna M.R. Andrade , Marcos A.V. Bittencourt , Roberto Salvatori , Evânio V. Silva , André L.M. Santos , Matheus M. Cunha , Wilton M. Takeshita , Alaíde H.A. Oliveira , Eugênia H.O. Valença , Alécia A. Oliveira-Santos , Luiz A. Oliveira-Neto
{"title":"Dental arches in inherited severe isolated growth hormone deficiency","authors":"Rafaela S. Girão , Manuel H. Aguiar-Oliveira , Bruna M.R. Andrade , Marcos A.V. Bittencourt , Roberto Salvatori , Evânio V. Silva , André L.M. Santos , Matheus M. Cunha , Wilton M. Takeshita , Alaíde H.A. Oliveira , Eugênia H.O. Valença , Alécia A. Oliveira-Santos , Luiz A. Oliveira-Neto","doi":"10.1016/j.ghir.2022.101444","DOIUrl":"10.1016/j.ghir.2022.101444","url":null,"abstract":"<div><h3>Objectives</h3><p><span>The growth of the dental arches depends on GH and insulin-like growth factor type 1 (IGF1), but the consequences of GH deficiency (GHD) on their growth are still unclear, probably due to the acquired etiology of GHD in most described series, often associated with additional pituitary deficits (thyrotrophic, corticotrophic and gonadotrophic hormones), and imperfections of related replacement therapies, which may affect the dental arch growth. To avoid these limitations, we took advantage of a unique cohort of subjects with isolated GH deficiency (IGHD) due the same mutation in the </span>GH releasing hormone<span> receptor gene<span>, living with very low serum GH and low to undetectable circulating IGF1 levels. Our purpose was to analyze the dimensions of maxillary and mandibular dental arches.</span></span></p></div><div><h3>Methods</h3><p>22 adult IGHD (15 untreated and 7 previously partially treated with GH) and 33 controls were enrolled in a cross-sectional study using the Ortho Insight 3D and MeshMixer software,</p></div><div><h3>Results</h3><p>In untreated IGHD subjects all maxillary arch measures were smaller than controls, while among mandibular arches, only the mandibular canine<span><span> width and the mandibular arch length were reduced. In partially GH treated subjects only the palate depth, the </span>maxillary canine width, the maxillary and mandibular arch lengths remained smaller than controls.</span></p></div><div><h3>Conclusions</h3><p>IGHD reduces the growth of maxillary arch to a greater degree than the mandibular arch, suggesting different control of superior and inferior dental arches. GH treatment increases some of these measures.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"62 ","pages":"Article 101444"},"PeriodicalIF":1.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39912507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stuart A. Morgan , Darlene E. Berryman , Edward O. List , Gareth G. Lavery , Paul M. Stewart , John J. Kopchick
{"title":"Regulation of 11β-HSD1 by GH/IGF-1 in key metabolic tissues may contribute to metabolic disease in GH deficient patients","authors":"Stuart A. Morgan , Darlene E. Berryman , Edward O. List , Gareth G. Lavery , Paul M. Stewart , John J. Kopchick","doi":"10.1016/j.ghir.2021.101440","DOIUrl":"10.1016/j.ghir.2021.101440","url":null,"abstract":"<div><p><span><span>Patients with growth hormone deficiency<span> (GHD) have many clinical features in common with Cushing's syndrome (glucocorticoid excess) – notably visceral obesity, insulin resistance, muscle </span></span>myopathy<span><span> and increased vascular mortality. Within key metabolic tissues, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to the active </span>glucocorticoid<span>, cortisol (11-dehydrocorticosterone and </span></span></span>corticosterone in rodents respectively), and thus amplifies local glucocorticoid action.</p><p>We hypothesize that 11β-HSD1 expression is negatively regulated by growth hormone (GH), and that GHD patients have elevated 11β-HSD1 within key metabolic tissues (leading to increased intracellular cortisol generation) which contributes to the clinical features of this disease.</p><p>To identify the impact of GH excess/resistance on 11β-HSD1 <em>in vivo</em><span><span><span>, we measured mRNA expression in key metabolic tissues of giant mice expressing the bovine GH (bGH) gene, dwarf mice with a disrupted </span>GH receptor (GHRKO) gene and mice expressing a gene encoding a GH </span>receptor antagonist<span> (GHA). Additionally, we assessed urine steroid markers of 11β-HSD1 activity in both GHRKO and bGH animals.</span></span></p><p><span>11β-HSD1 expression was decreased in gastrocnemius muscle (0.43-fold, </span><em>p</em><span> < 0.05), subcutaneous adipose (0.53-fold, </span><em>p</em> < 0.05) and epididymal adipose tissue (0.40-fold, <em>p</em> < 0.05), but not liver, in bGH mice compared to WT controls. This was paralleled by an increased percentage of 11-DHC (inactive glucocorticoid) present in the urine of bGH mice compared to WT controls (2.5-fold, <em>p</em> < 0.01) - consistent with decreased systemic 11β-HSD1 activity. By contrast, expression of 11β-HSD1 was increased in the liver of GHRKO (2.7-fold, <em>p</em> < 0.05) and GHA mice (2.0-fold, <em>p</em> < 0.05) compared to WT controls, but not gastrocnemius muscle, subcutaneous adipose tissue or epididymal adipose tissue.</p><p>In summary, we have demonstrated a negative relationship between GH action and 11β-HSD1 expression which appears to be tissue specific. These data provide evidence that increased intracellular cortisol production within key tissues may contribute to metabolic disease in GHD patients.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"62 ","pages":"Article 101440"},"PeriodicalIF":1.4,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39651866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}