Yueyang Liu, Rong Fu, Hui Jia, Kefan Yang, Fu Ren, Ming-Sheng Zhou
{"title":"GHRH and its analogues in central nervous system diseases.","authors":"Yueyang Liu, Rong Fu, Hui Jia, Kefan Yang, Fu Ren, Ming-Sheng Zhou","doi":"10.1007/s11154-024-09920-x","DOIUrl":"https://doi.org/10.1007/s11154-024-09920-x","url":null,"abstract":"<p><p>Growth hormone-releasing hormone (GHRH) is primarily produced by the hypothalamus and stimulates the release of growth hormone (GH) in the anterior pituitary gland, which subsequently regulates the production of hepatic insulin-like growth factor-1 (IGF-1). GH and IGF-1 have potent effects on promoting cell proliferation, inhibiting cell apoptosis, as well as regulating cell metabolism. In central nerve system (CNS), GHRH/GH/IGF-1 promote brain development and growth, stimulate neuronal proliferation, and regulate neurotransmitter release, thereby participating in the regulation of various CNS physiological activities. In addition to hypothalamus-pituitary gland, GHRH and GHRH receptor (GHRH-R) are also expressed in other brain cells or tissues, such as endogenous neural stem cells (NSCs) and tumor cells. Alternations in GHRH/GH/IGF-1 axis are associated with various CNS diseases, for example, Alzheimer's disease, amyotrophic lateral sclerosis and emotional disorders manifest GHRH, GH or IGF-1 deficiency, and GH or IGF-1 supplementation exerts beneficial therapeutic effects on these diseases. CNS tumors, such as glioma, can express GHRH and GHRH-R, and activating this signaling pathway promotes tumor cell growth. The synthesized GHRH antagonists have shown to inhibit glioma cell growth and may hold promising as an adjuvant therapy for treating glioma. In addition, we have shown that GHRH agonist MR-409 can improve neurological sequelae after ischemic stroke by activating extrapituitary GHRH-R signaling and promoting endogenous NSCs-derived neuronal regeneration. This article reviews the involvement of GHRH/GH/IGF-1 in CNS diseases, and potential roles of GHRH agonists and antagonists in treating CNS diseases.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Meal replacements on obesity and leptin: a systematic review and meta-analysis.","authors":"Somaye Fatahi, Danial Fotros, Mohammad Hassan Sohouli, Koroush Vahidshahi, Pejman Rohani, Nathalia Sernizon Guimarães","doi":"10.1007/s11154-024-09918-5","DOIUrl":"https://doi.org/10.1007/s11154-024-09918-5","url":null,"abstract":"<p><p>The global prevalence of obesity and overweight is a significant concern in the field of public health. Numerous interventional studies have been conducted to assess the possible meal replacements (MRs) effect on anthropometric indicators and indices and laboratory test that reflect obesity. However, there are no comprehensive results in this field. The study aim was to understand the possible effects of MRs on body weight, body mass index (BMI), fat mass, waist circumferences (WC), and leptin levels. A systematic search was conducted in five electronic databases in order to find randomized clinical trials (RCTs) that examined the possible MRs effect on obesity. Analyses were performed in R software, version 4.2.1. The random-effects model analysis was used to provide pooled mean difference and 95% confidence intervals (95% CI). Seventy studies were included. Body weight (WMD: -3.35 kg, 95% CI: -4.28 to -2.42), BMI (WMD: -1.12 kg/m2, 95% CI: -1.51 to -0.72), fat mass (WMD: -2.77 kg, 95% CI: -3.59 to -1.6), WC (WMD: -2.82 cm, 95% CI: -3.51 to -2.12) were significantly reduced after MRs compared to control. No significant effect was observed on leptin (WMD: -3.37 ng/ml, 95% CI: -8.23 to 1.49). Subgroup analyses indicated that impact of total MRs on anthropometric factors was greater in comparison to partial MRs. Considering other lifestyle factors, MRs can lead to anthropometric indicators and indices reduction.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"What do we know about abnormally low prolactin levels in polycystic ovary syndrome? A narrative review.","authors":"Nicoletta Cera, Joana Pinto, Duarte Pignatelli","doi":"10.1007/s11154-024-09912-x","DOIUrl":"https://doi.org/10.1007/s11154-024-09912-x","url":null,"abstract":"<p><p>Hyper and hypoprolactinemia seem to be related to the occurrence of metabolic alterations in PCOS patients. In contrast, between significantly elevated and significantly low, prolactin levels seem to be protective against metabolic consequences. In the present review, we found 4 studies investigating hypoprolactinemia in patients with PCOS. We also identified 6 additional studies that reported low levels of PRL in PCOS patients. Although its prevalence is not considered high (13.2-13.9%), its contribution is certainly significant to the metabolic alterations observed in PCOS (insulin resistance, obesity, diabetes mellitus, and fatty liver disease). Dopamine inhibits the secretion of prolactin and GnRH. If dopamine levels are low or the dopamine receptor is less expressed or mutated, the levels of prolactin and GnRH increase, and consequently, LH also increases. On the other hand, hyperprolactinemia, in prolactinomas-typical levels, acting through kisspeptin inhibition causes GnRH suppression and hypogonadotropic hypogonadism. In situations of hypoprolactinemia due to excessive dopamine agonist treatment, dosage reduction is important to minimize the decrease in prolactin levels. Nevertheless, there is a lack of prospective studies confirming these hypotheses, as well as randomized clinical trials with appropriate drugs targeting both hyperprolactin and hypoprolactin in patients with PCOS.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iacopo Gesmundo, Francesca Pedrolli, Renzhi Cai, Wei Sha, Andrew V Schally, Riccarda Granata
{"title":"Growth hormone-releasing hormone and cancer.","authors":"Iacopo Gesmundo, Francesca Pedrolli, Renzhi Cai, Wei Sha, Andrew V Schally, Riccarda Granata","doi":"10.1007/s11154-024-09919-4","DOIUrl":"https://doi.org/10.1007/s11154-024-09919-4","url":null,"abstract":"<p><p>The hypothalamic hormone growth hormone-releasing hormone (GHRH), in addition to promoting the synthesis and release of growth hormone (GH), stimulates the proliferation of human normal and malignant cells by binding to GHRH-receptor (GHRH-R) and its main splice variant, SV1. Both GHRH and GHRH-Rs are expressed in various cancers, forming a stimulatory pathway for cancer cell growth; additionally, SV1 possesses ligand independent proliferative effects. Therefore, targeting GHRH-Rs pharmacologically has been proposed for the treatment of cancer. Various classes of synthetic GHRH antagonists have been developed, endowed with strong anticancer activity in vitro and in vivo, in addition to displaying anti-inflammatory, antioxidant and immune-modulatory functions. GHRH antagonists exert indirect effects by blocking the pituitary GH/hepatic insulin-like growth factor I (IGF-I) axis, or directly inhibiting the binding of GHRH on tumor GHRH-Rs. Additionally, GHRH antagonists block the mitogenic functions of SV1 in tumor cells. This review illustrates the main findings on the antitumor effects of GHRH antagonists in experimental human cancers, along with their underlying mechanisms. The development of GHRH antagonists, with reduced toxicity and high stability, could lead to novel therapeutic agents for the treatment of cancer and inflammatory diseases.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joel Costoya, Simonetta I Gaumond, Ravinder S Chale, Andrew V Schally, Joaquin J Jimenez
{"title":"A novel approach for the treatment of AML, through GHRH antagonism: MIA-602.","authors":"Joel Costoya, Simonetta I Gaumond, Ravinder S Chale, Andrew V Schally, Joaquin J Jimenez","doi":"10.1007/s11154-024-09917-6","DOIUrl":"https://doi.org/10.1007/s11154-024-09917-6","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is the most aggressive and prevalent form of leukemia in adults. The gold-standard intervention revolves around the use of chemotherapy, and in some cases hematopoietic stem cell transplantation. Drug resistance is a frequent complication resulting from treatment, as it stands there are limited clinical measures available for refractory AML besides palliative care. The goal of this review is to renew interest in a novel targeted hormone therapy in the treatment of AML utilizing growth hormone-releasing hormone (GHRH) antagonism, given it may provide a potential solution for current barriers to achieving complete remission post-therapy. Recapitulating pre-clinical evidence, GHRH antagonists (GHRH-Ant) have significant anti-cancer activity across experimental human AML cell lines in vitro and in vivo and demonstrate significant inhibition of cancer in drug resistant analogs of leukemic cell lines as well. GHRH-Ant act in manners that are orthogonal to anthracyclines and when administered in combination synergize to produce a more potent anti-neoplastic effect. Considering the adversities associated with standard AML therapies and the developing issue of drug resistance, MIA-602 represents a novel approach worth further investigation.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The molecular basis of hypoprolactinaemia.","authors":"Bryan Padraig Finn, Mehul T Dattani","doi":"10.1007/s11154-024-09906-9","DOIUrl":"https://doi.org/10.1007/s11154-024-09906-9","url":null,"abstract":"<p><p>Hypoprolactinaemia is an endocrinopathy which is typically encountered as part of a combined pituitary hormone deficiency picture. The vast majority of genetic causes identified to date have been in the context of congenital hypopituitarism with multiple co-existent endocrinopathies. This is primarily with its closest hormonal relation, namely growth hormone. Acquired hypoprolactinaemia is generally rare in paediatric patients, and usually occurs together with other hormonal deficiencies. Congenital hypopituitarism occurs with an incidence of 1:4,000-10,000 cases and mutations in the following transcription factors account for the majority of documented genetic causes: PROP-1, POU1F1, LHX3/4 as well as documented case reports for a smaller subset of transcription factors and other molecules implicated in lactotroph development and prolactin secretion. Isolated prolactin deficiency has been described in a number of sporadic case reports in the literature, but no cases of mutations in the gene have been described to date. A range of genetic polymorphisms affecting multiple components of the prolactin signalling pathway have been identified in the literature, ranging from RNA spliceosome mutations (RNPC3) to loss of function mutations in IGSF-1. As paediatricians gain a greater understanding of the long-term ramifications of hypoprolactinaemia in terms of metabolic syndrome, type 2 diabetes mellitus and impaired fertility, the expectation is that clinicians will measure prolactin more frequently over time. Ultimately, we will encounter further reports of hypoprolactinaemia-related clinical presentations with further genetic mutations, in turn leading to a greater insight into the molecular basis of hypoprolactinaemia in terms of signalling pathways and downstream mediators. In the interim, the greatest untapped reserve of genetic causes remains within the phenotypic spectrum of congenital hypopituitarism.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The homeo-FIT-prolactin hypothesis: the role of prolactin in metabolic homeostasis - association or causality?","authors":"Jesper Krogh","doi":"10.1007/s11154-024-09916-7","DOIUrl":"https://doi.org/10.1007/s11154-024-09916-7","url":null,"abstract":"<p><p>The homeo-fit-prolactin hypothesis proposes a causal metabolic role for prolactin with hypoprolactinemia and hyperprolactinemia leading to adverse metabolic alterations. However, prolactin within the normal range and up to four times the upper reference limit may be a consequence of metabolic adaption and have a positive metabolic role similar to increased insulin in pre-diabetes. As a consequence, drugs that would increase prolactin levels within this threshold may hold promising effects, particularly for patients with type 2 diabetes. A documented positive metabolic effect of prolactin just above the normal threshold would not just be of benefit to patients with diabetes but assist in the decision to treat mild hyperprolactinemia in other patient groups as well, e.g. drug-induced hyperprolactinemia or idiopathic hyperprolactinemia. Prolactin receptors are present in the pancreas, liver, and adipose tissue, and pre-clinical studies suggest a positive and causal effect of prolactin on the gluco-insulinemic profile and lipid metabolism. This narrative review examines the evidence for the homeo-fit-prolactin hypothesis with a particular focus on results from human studies.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yibing Chen, Qian Jiang, Xiaowei Xing, Tao Yuan, Pingping Li
{"title":"Clinical research progress on β-cell dysfunction in T2DM development in the Chinese population.","authors":"Yibing Chen, Qian Jiang, Xiaowei Xing, Tao Yuan, Pingping Li","doi":"10.1007/s11154-024-09914-9","DOIUrl":"https://doi.org/10.1007/s11154-024-09914-9","url":null,"abstract":"<p><p>The prevalence of type-2 diabetes mellitus (T2DM) has increased over 10-fold in the past 40 years in China, which now has the largest T2DM population in the world. Insulin resistance and β-cell dysfunction are the typical features of T2DM. Although both factors play a role, decreased β-cell function and β-cell mass are the predominant factors for progression to T2DM. Considering the differences between Chinese T2DM patients and those of other ethnicities, it is important to characterize β-cell dysfunction in Chinese patients during T2DM progression. Herein, we reviewed the studies on the relationships between β-cell function and T2DM progression in the Chinese population and discussed the differences among individuals of varying ethnicities. Meanwhile, we summarized the risk factors and current treatments of T2DM in Chinese individuals and discussed their impacts on β-cell function with the hope of identifying a better T2DM therapy.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Agnieszka Siejka, Hanna Lawnicka, Saikat Fakir, Nektarios Barabutis
{"title":"Growth hormone - releasing hormone in the immune system.","authors":"Agnieszka Siejka, Hanna Lawnicka, Saikat Fakir, Nektarios Barabutis","doi":"10.1007/s11154-024-09913-w","DOIUrl":"10.1007/s11154-024-09913-w","url":null,"abstract":"<p><p>GHRH is a neuropeptide associated with a diverse variety of activities in human physiology and immune responses. The present study reviews the latest information on the involvement of GHRH in the immune system and inflammation, suggesting that GHRH antagonists may deliver a new therapeutic possibility in disorders related to immune system dysfunction and inflammation.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prolactin deficiency in the context of other pituitary hormone abnormalities : Special issue: hypoprolactinemia: a neglected endocrine disorder.","authors":"Ilan Shimon","doi":"10.1007/s11154-024-09902-z","DOIUrl":"https://doi.org/10.1007/s11154-024-09902-z","url":null,"abstract":"<p><p>Prolactin deficiency is rare. It generally occurs when pituitary disorders, such as large pituitary tumors, pituitary apoplexy, and other conditions associated with sellar mass effect lead to global failure of pituitary function and hypopituitarism. In these situiations, prolactin is commonly the last pituitary hormone affected, after growth hormone and gonadotropins are lost and thyroid-stimulating hormone and adrenocorticotopic hormone secretion is impaired. Prolactin deficiency accompanies several congenital syndromes due to mutations in PROP1 and Pit1/ POU1F and in X-linked IGSF1 deficiency syndrome, and several aqcuired conditions including Sheehan syndrome, IgG4-related hypophysitis, and immune checkpoint-inhibitor-induced hypophysitis. In women, prolactin deficiency prevents lactation following childbirth among other symptoms associated with hypopituitarism. Human prolactin is not available commercially as replacement therapy. However, recombinant human prolactin administered daily to women with hypoprolactinemia and alactogenesis was found to lead to the production of significant milk volume sufficient for lactation.</p>","PeriodicalId":21106,"journal":{"name":"Reviews in Endocrine & Metabolic Disorders","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}