Reviews in Endocrine & Metabolic Disorders最新文献

Despite initial discovery in pancreatic tumors, GHRH is a 44-amino acid peptide primarily expressed in the hypothalamus. Recent RNA sequencing clarifies GHRH expression: predominantly hypothalamic in humans, with some basal ganglia presence, while extending to additional central nervous system (CNS) regions in other species. GHRH binds to its G-protein coupled receptor (GHRHR) in the arcuate (ARC), ventromedial (VMH), and periventricular (PeN) nuclei of the hypothalamus to exert its effects. Notably, the highest non-brain expression is found in somatotroph cells of the pituitary, directly targeting growth hormone (GH) production. GHRH is the primary regulator of pulsatile GH secretion, counteracted by somatostatin. While early models proposed alternating GHRH/somatostatin bursts, others implicate somatostatin as the primary regulator of GH pulse timing. These models fail to fully explain species and gender differences, particularly regarding nutritional status. The discovery of ghrelin, acting via GHS-R1a on GHRH neurons, significantly advanced understanding of GH regulation. Ghrelin interacts intricately with GHRH, modulating its expression and neuronal activity. Ghrelin also exerts GHRH-independent GH stimulation and synergizes with GHRH. The crucial role of GHRH in GH regulation is demonstrated by its key involvement in the action of other GH regulators, such as leptin, neuropeptide Y (NPY), and orexins. However, these interactions have also revealed that the physiological effects of GHRH extend far beyond its canonical role as a GH secretagogue. In this context, GHRH is thought to be a key regulator of the sleep-wake cycle and may be involved in whole-body energy homeostasis. The objective of this review is to summarize the current knowledge on GHRH and to discuss the potential pleiotropic effect of this hypothalamic neuropeptide, far beyond its classical action as regulator of the somatotroph axis.

Growth hormone-releasing hormone (GHRH) is a crucial endocrine hormone that exerts its biological effects by binding to specific receptors on the cell surface, known as GHRH receptors (GHRH-R). This binding activates downstream signaling pathways. In addition to promoting growth hormone secretion by the pituitary gland, GHRH also functions to maintain multisystem homeostasis by interacting with peripheral tissues that express GHRH-R. Due to the multiple roles of GHRH in body development and tissue repair, a variety of GHRH analogue peptides have been synthesized. Based on their effects on GHRH-R, these GHRH analogues can be classified as GHRH-R agonists and antagonists. Recently, the interaction of GHRH and its analogues with blood vessels, such as promoting angiogenesis and inhibiting vascular calcification (VC), has gained significant attention. This article reviews the effects of GHRH and its analogues on blood vessels.

The hypothalamic polypeptide growth hormone-releasing hormone (GHRH) stimulates the secretion of growth hormone (GH) from the pituitary through binding and activation of the pituitary type of GHRH receptor (GHRH-R), which belongs to the family of G protein-coupled receptors with seven potential membrane-spanning domains. Various splice variants of GHRH-R (SV) in human neoplasms and other extrapituitary tissues were demonstrated and their cDNA was sequenced. Among the SVs, splice variant 1 (SV1) possesses the greatest similarity to the full-length GHRH-R and remains functional by eliciting cAMP signaling and mitogenic activity upon stimulation by GHRH. In this review, we briefly discuss the activation, regulation, molecular mechanisms and signaling pathways of GHRH-Rs and their SVs in various tissues and also summarize the expression, biological activities and potential function of GHRH, its analogs and their receptors. A large body of work have extensively studied and evaluated potential clinical applications of agonists and antagonists of GHRH in diverse fields, including oncology, endocrinology, obesity, diabetes, other metabolic dysfunctions, cardiology, immune functions, mood disorders, Alzheimer's and lung disease, ophthalmology, inflammation, wound healing and other applications. These results strongly support the potential therapeutic use of GHRH analogs in human medicine in the near future.

As evidenced by the clinical symptoms in hyper- or hypothyroidism, thyroid hormones have strong effects on cardiovascular and metabolic functions. While these actions had been initially attributed to direct molecular mechanisms in the respective peripheral tissues such as heart, muscle or adipose tissue, a recent paradigm shift has occurred with accumulating observations that demonstrated important indirect effects via the brain on these systems. However, the individual contributions of the peripheral versus central thyroid hormone actions for the well-known phenotypical symptoms are still not entirely understood. Similarly, the neuroanatomical substrates for these central actions have remained largely enigmatic, although many studies point to the hypothalamus as a major target of thyroid hormone action. This review critically discusses the role of the central actions of thyroid hormone for the regulation of heart rate, body temperature, energy expenditure and food intake, and integrates some novel findings to summarize the current state of the field.

Multiple guidelines for thyroid nodule management have been developed by endocrinologists, often in collaboration with surgeons and radiologists. While there is now a lot of scientific information available to meet the needs of healthcare providers, there is not always uniformity and standardization among recommendations. Consequently, the interpretation and application of guidelines in clinical practice remain somewhat limited. In this context, the management of "small" thyroid nodule warrants full discussion. Looking at treatment guidelines, surgery is the first-line option and the risk of cancer relapse can be assessed only after at least thyroidectomy; in addition, according to guidelines of minimally invasive treatment, thermal ablation may be considered for patients with small classical papillary carcinoma. However, the Thyroid Imaging Reporting And Data Systems do not recommend biopsy in nodules less than 1 cm; and performing biopsy may yield a result that is suspicious or consistent with malignancy without specifying the cancer subtype. With these premises, facing cases of "small" nodule less than 1 cm is challenging. Even if the recommendations of guidelines sound singularly appropriate, they may seem conflicting. Coordinated guidelines are needed.

Purpose: Hypoestrogenism is associated with loss of bone mass and strength. Melatonin has become a strategy due to its actions on bone tissue. This review summarizes the available data on the effects of chronic melatonin administration on bone tissue in animal models with hypoestrogenism.

Data sources: A systematic search of the PubMed, Web of Science, and Scopus, databases up to November 27, 2023, was conducted using specified key terms and Boolean operators (bone AND bones OR bone density OR bone diseases OR osteogenesis OR osteoporosis AND melatonin).

Study selection: only controlled studies in English and with rodents.

Study design: systematic review.

Data extraction: animals' characteristics (sex and hypoestrogenism confirmation), dose, route, and duration of administration of melatonin, and outcomes from the properties of bone.

Results: A total of 25 studies were identified after the screening process. In the hypoestrogenic state, melatonin administration improved bone mineral density, bone volume ratio, trabecular number in 19 studies, and maximal load/strength and stiffness test in 7. 4 studies reported improved matrix mineralization in bone marrow mesenchymal stem cells. Melatonin increased the expression of RUNX2 in 9 studies, OCN in 6, and OPG in 4, while decreasing RANKL in 3. In 4 studies the melatonin increased the serum osteocalcin levels.

Conclusion: Chronic administration of melatonin appears to improve the biophysical, biomechanical, molecular, and biochemical properties of bone tissue. These benefits promote an osteogenic effect, making melatonin an efficient strategy to preserve microarchitecture and tissue mass in a state of hypoestrogenism.

Neuroendocrine tumors (NETs) are a diverse group of neoplasms whose prevalence is increasing globally, primarily due to advancements in diagnostic techniques. NETs arise from cells of the diffuse endocrine system and can occur in various locations, with the gastrointestinal tract being the most common. Their diverse clinical presentations, which range from asymptomatic to severe hormone-induced syndromes, pose significant diagnostic challenges. In emergency care, prompt recognition and management of complications such as bowel obstruction, ischemic events, hormonal crises, and metastases are critical. This review discusses the radiologic spectrum of NETs in emergent care, emphasizing the role of imaging in timely diagnosis and intervention.

An 'adenoma' is a benign neoplasm composed of epithelial tissue, and has been standard nomenclature for primary pituitary neoplasms. In 2022, the fifth edition of the WHO Classification of Endocrine Tumours and of Central Nervous System Tumours, renamed pituitary adenomas as neuroendocrine tumours (NETs), assigning an oncology label to pituitary invariably benign neoplasms. Multidisciplinary workshops convened by the Pituitary Society have questioned the process, validity, and merit of this arbitrary change, while addressing the adverse clinical implications of the proposed new nomenclature. Unlike NETs, pituitary adenomas are highly prevalent, indolent and very rarely become malignant, and in general do not affect life expectancy when appropriately managed. A nomenclature change to NET does not advance mechanistic insight, treatment or prognosis but confers a misleading oncology connotation, potentially leading to overtreatment as well as engendering unnecessary patient anxiety. As the majority of pituitary adenomas do not require surgery, exclusion of these disorders is a major shortcoming of the pathology-based WHO classification system which is limited to patients undergoing surgery. Many factors influence prognosis other than histopathology. A new clinical classical classification has been developed for guiding prognosis and therapy of pituitary adenomas by integrating clinical, genetic, biochemical, radiological, pathological, and molecular information for all adenomas arising from anterior pituitary cell lineages. The system uses an evidence-based scoring of risk factors to yield a cumulative grade score that reflects disease severity. It can be used at the bedside to guide pituitary adenoma management. Once validated in prospective studies, this simple classification system could provide a standardised platform for assessing disease severity, prognosis, and effects of therapy on pituitary adenoma outcomes.

The prostate gland is an endocrine-sensitive organ responding to multiple stimuli. Its development and function are regulated by multiple hormones (i.e. steroids such as androgens, estrogens and glucocorticoids) but also by other key hormonal systems such as those comprised by insulin-like growth factor 1 and insulin, which are sourced by different tissues [e.g. testicles/adrenal-gland/adipose-tissue/liver/pancreas, etc.). Particularly important for the endocrine control of prostatic pathophysiology and anatomy are hormones produced and/or secreted by different cell types of the pituitary gland [growth-hormone, luteinizing-hormone, follicle-stimulating hormone, and prolactin, oxytocin, arginine-vasopressin and melanocyte-stimulating hormone], which affect prostate gland function either directly or indirectly under physiological and pathophysiological conditions [e.g. metabolic dysregulation (e.g. obesity), and prostate transformations (e.g. prostate cancer)]. This review summarizes the impact of all pituitary hormone types on prostate gland under these diverse conditions including in vivo and in vitro studies.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has short- and long-term adverse effects. Therefore, further exploration of the pathophysiology of GDM and related biomarkers is important. In this study, we performed a systematic review and meta-analysis to investigate the associations between metabolites in blood detected via metabolomics techniques and the risk of GDM and to identify possible biomarkers for predicting the occurrence of GDM. We retrieved case‒control and cohort studies of metabolomics and GDM published in PubMed, Embase, and Web of Science through March 29, 2024; extracted metabolite concentrations, odds ratios (ORs), or relative risks (RRs); and evaluated the integrated results with metabolites per-SD risk estimates and 95% CIs for GDM. We estimated the results via the random effects model and the inverse variance method. Our study is registered in PROSPERO (CRD42024539435). We included a total of 28 case‒control and cohort studies, including 17,370 subjects (4,372 GDM patients and 12,998 non-GDM subjects), and meta-analyzed 67 metabolites. Twenty-five of these metabolites were associated with GDM risk. Some amino acids (isoleucine, leucine, valine, alanine, aspartate, etc.), lipids (C16:0, C18:1n-9, C18:1n-7, lysophosphatidylcholine (LPC) (16:0), LPC (18:0), and palmitoylcarnitine), and carbohydrates and energy metabolites (glucose, pyruvate, lactate, 2-hydroxybutyrate, 3-hydroxybutyrate) were discovered to be associated with increased GDM risk (hazard ratio 1.06-2.77). Glutamine, histidine, C14:0, and sphingomyelin (SM) (34:1) were associated with lower GDM risk (hazard ratio 0.75-0.84). These findings suggest that these metabolites may play essential roles in GDM progression, and serve as biomarkers, contributing to the early diagnosis and prediction of GDM.