Growth Hormone Release Research Articles

GHRH and reproductive systems: Mechanisms, functions, and clinical implications.

Growth hormone-releasing hormone (GHRH) has classically been considered a regulatory neuropeptide of the hypothalamic-pituitary system, which mediates its anabolic effects through hepatic GH/IGF-I axis. However, during the last decades it has been demonstrated that this key regulatory hormone may be produced in numerous peripheral tissues outside the central nervous system, participating in fundamental physiological functions through a complex balance between its purely endocrine action, and the recently local (autocrine/paracrine) discovered role. Among peripheral sites, its presence in the male and female reproductive systems stands out. In this review, we will first explore the role of the GHRH/GHRH-R hormone axis as a central player in the gonadal function; then, we will discuss available information regarding the presence of GHRH/GHRH-R and the potential physiological roles in reproductive systems of various species; and finally, we will address how reproductive system-related disorders-such as infertility problems, endometriosis, or tumor pathologies (including prostate, or ovarian cancer)-could benefit from hormonal interventions related to the manipulation of the GHRH axis.

Reducing Cardiovascular Risk in HIV: The Unseen Impact of Visceral Fat

While modern antiretroviral therapy (ART) for people with HIV (PWH) increases life expectancy, there is still an increased risk of developing cardiovascular disease (CVD) in this population. As one factor associated with this increased risk is excess visceral abdominal fat (EVAF), the Visceral Adiposity Measurement and Observations Study (VAMOS) aimed to assess the impact of EVAF on CVD risk in PWH taking modern ART. Participants were grouped according to visceral adipose tissue (VAT) surface area <130 cm2 (non-EVAF group) or ≥130 cm2 (EVAF group), quantified by CT scan. Findings presented at IDWeek 2024 revealed significant differences between EVAF and non-EVAF groups in 10-year atherosclerotic CVD (ASCVD) risk score, as well as many of their individual components. VAMOS also showed correlations between increasing VAT surface area and increasing 10-year ASCVD risk score and insulin resistance measures. Accordingly, VAT may represent a targetable factor to reduce ASCVD risk. Also shown was an inverse relationship between growth hormone (GH) levels and VAT surface area. As GH reductions related to obesity are associated with elevated CVD risk, increasing GH levels may consequently reduce ASCVD risk score. Analysis of two Phase III trials of the GH-releasing hormone (GHRH) analogue tesamorelin, which can significantly reduce VAT in PWH, was also presented at IDWeek 2024. A significant overall trend in 10-year ASCVD risk score reduction was shown in tesamorelin-treated participants, around half of which were already taking lipid lowering therapies. This suggests a benefit of targeting and reducing EVAF to further impact ASCVD risk.

The development of growth hormone-releasing hormone analogs: Therapeutic advances in cancer, regenerative medicine, and metabolic disorders.

Growth Hormone-Releasing Hormone (GHRH) and its analogs have gained significant attention for their therapeutic potential across various domains, including oncology, regenerative medicine, and metabolic disorders. Originally recognized for its role in regulating growth hormone (GH) secretion, GHRH has since been discovered to exert broader physiological effects beyond the pituitary gland, with GHRH receptors identified in multiple extrahypothalamic tissues, including tumor cells. This review explores the development of both GHRH agonists and antagonists, focusing on their mechanisms of action, therapeutic applications, and future potential. GHRH agonists have shown promise in promoting tissue regeneration, improving cardiac function, and enhancing islet survival in diabetes. Meanwhile, GHRH antagonists, particularly those in the MIA and AVR series, demonstrate potent antitumor activity by inhibiting cancer cell proliferation and downregulating growth factor pathways, while also exhibiting anti-inflammatory properties. Preclinical studies in models of lung, prostate, breast, and gastrointestinal cancers indicate that GHRH analogs could offer a novel therapeutic approach with minimal toxicity. Additionally, GHRH antagonists are being investigated for their potential in treating neurodegenerative diseases and inflammatory conditions. This review highlights the versatility of GHRH analogs as a promising class of therapeutic agents, poised to impact multiple fields of medicine.

Impact of Full-Spectrum and Infrared Lighting on Growth, Oxidative Stress, and Cecal Microbiota in Broilers

Lighting is crucial for the development of broilers as it affects their growth performance, oxidative stress, and overall health. This study investigates the impact of full-spectrum light, infrared light, and LED white light exposure on the growth performance, oxidative stress markers, and cecal microbiota of medium-growth yellow-feathered broilers. A total of 216 medium-growth yellow-feathered chicks (Yuhuang No. 5), five days old, were randomly divided into three groups: 72 chicks in each group, with three replicates of 24 chicks. The birds were raised under different lighting conditions, including LED infrared light (II), full-spectrum therapy light (FB), and LED white light (CG) until day 87. This experiment comprised the early growth phase and measured critical hormones such as Melatonin (Mel), Growth Hormone (GH), and Growth Hormone Releasing Hormone (GHRH), as well as Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Catalase (CAT). Additionally, this study examined the differences in microbiota diversity and composition. The results demonstrated that LED infrared and full-spectrum light exposure significantly (p < 0.05) increased broiler body weight. Particularly, full-spectrum light was effective in comb redness and reducing final comb length and oxidative stress. Furthermore, full-spectrum light improved microbial prosperity and diversity compared with the other lighting conditions. Overall, the findings suggest that full-spectrum lighting is more beneficial for broiler growth, reducing oxidative stress, and promoting gut health compared with LED infrared lighting. These insights can be applied to optimizing broiler farming practices, thereby improving productivity and animal welfare.

Effects of GHRH and its analogues on the Vascular System.

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.

GHRH in diabetes and metabolism.

Despite over a century of insulin therapy and recent advances in glucose monitoring, diabetes and its complications remain a significant burden. Current medications are not durable, with symptoms often returning after treatment ends, and responses vary between patients. Additionally, the effectiveness of many medications diminishes over time, highlighting the need for alternative approaches. Maintaining β-cell mass and promoting β-cell regeneration offer more curable treatments, while cell replacement therapies could be an option if regeneration is not feasible. For both strategies, enhancing β-cell survival is crucial. Growth hormone-releasing hormone (GHRH) was originally discovered for its ability to stimulate the production and release of growth hormone (GH) from the pituitary. Beyond the hypothalamus, GHRH is produced in peripheral tissues, with its receptor, GHRHR, expressed in tissues such as the pituitary, pancreas, adipose tissue, intestine, and liver. Several studies have shown that GHRH and its analogs enhance the survival of insulin-producing pancreatic β-cells both in vitro and in animal models. These beneficial effects strongly support the potential of GHRH agonists and antagonists for the clinical treatment of human metabolic diseases or for enhancing β-cell survival in cells used for transplantation. In the current review, we will discuss the roles of hypothalamic and extrahypothalamic GHRH in metabolism in physiological and pathological contexts, along with the underlying mechanisms. Furthermore, we will discuss the potential beneficial effects of GHRH analogs for the treatment of metabolic diseases.

Regulatory Effects of Copper on Ghrelin Secretion in Rat Fundic Glands.

Copper (Cu) is an effective additive in feed for promoting growth. Growth dan axis comprising growth hormone (GH), somatostatin (SS) and GH-releasing hormone (GHRH), with ghrelin regulating their release. The growth-promoting effects of Cu are closely related to ghrelin, but the specific mechanism behind the relationship remains unknown. We investigated the adjustment of ghrelin synthesis and secretion by Cu. Sprague-Dawley rats were fed basal diets with an addition of 0, 120 or 240 mg/kg Cu sulfate for 28 day to establish a growth-promoting model. Signalling molecules relevant to ghrelin synthesis and secretion were detected and mechanistically explored using enzyme-linked immunosorbent assay, quantitative reverse-transcription polymerase chain reaction and Western blot analysis. The 120 mg/kg supplement improved growth performance; significantly increased the serum levels of ghrelin, ghrelin O-acyltransferase (GOAT), acylated ghrelin (AG), GH, and reactive oxygen species (ROS) and decreased those of SS; significantly increased the mRNA and protein expression of ghrelin, GOAT, ghrelin receptor (GHS-R1α), and activator protein 1 (AP-1); increased the phosphorylation ratio of JNK and p38 MAPK; and inhibited the mRNA and protein expression of SS and SS receptor subtype 2 (SSTR2) in gastric fundic gland tissues. Thus, Cu may affect gastric ghrelin synthesis at the transcriptional level by activating the JNK/p38 MAPK pathway through increased ROS levels and regulating the activation of the downstream redox-sensitive transcription factor AP-1. SS plays a crucial determinant role in ghrelin regulation via intragastric Cu. Cu promotes GOAT activity and ghrelin secretion by inhibiting SS secretion, affecting AG levels, and promoting ghrelin acylation through ghrelin/GOAT/GHS-R1α system, modulating ghrelin secretion.

Growth hormone-releasing hormone and its analogues in health and disease.

Growth hormone-releasing hormone (GHRH) and its ability to stimulate the production and release of growth hormone from the pituitary were discovered more than four decades ago. Since then, this hormone has been studied extensively and research into its functions is still ongoing. GHRH has multifaceted roles beyond the originally identified functions that encompass a variety of direct extrapituitary effects. In this Review, we illustrate the different biological activities of GHRH, covering the effects of GHRH agonists and antagonists in physiological and pathological contexts, along with the underlying mechanisms. GHRH and GHRH analogues have been implicated in cell growth, wound healing, cell death, inflammation, immune functions, mood disorders, feeding behaviour, neuroprotection, diabetes mellitus and obesity, as well as cardiovascular, lung and neurodegenerative diseases and some cancers. The positive effects observed in preclinical models in vitro and in vivo strongly support the potential use of GHRH agonists and antagonists as clinical therapeutics.

GHRH and the prostate.

In the late 1960s and early 1970s, hypothalamic regulatory hormones were isolated, characterized and sequenced. Later, it was demonstrated hypothalamic and ectopic production of growth hormone-releasing hormone (GHRH) in normal and tumor tissues, of both humans and animals. Pituitary-type GHRH receptors (pGHRH-R) had been demonstrated to be expressed predominantly in the anterior pituitary gland but also found in other somatic cells, and significantly present in various human cancers; in addition, the expression of splice variants (SVs) of GHRH receptor (GHRH-R) has been found not only in the pituitary but in extrapituitary tissues, including human neoplasms. In relation to the prostate, besides the pGHRH-R, it has been detected the presence of truncated splice variants of GHRH-R (SV1-SV4) in normal human prostate and human prostate cancer (PCa) specimens; lastly, a novel SV of GHRH-R has been detected in human PCa. Signaling pathways activated by GHRH include AC/cAMP/PKA, Ras/Raf/ERK, PI3K/Akt/mTOR and JAK2/STAT3, which are involved in processes such as cell survival, proliferation and cytokine secretion. The neuropeptide GHRH can also transactivate the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER)-2. Thus, GHRH-Rs have become drug targets for several types of clinical conditions, including prostate-related conditions such as prostatitis, benign hyperplasia and cancer. Over the last fifty years, the development of GHRH-R receptor antagonists has been unstoppable, improving their potency, stability and affinity for the receptor. The last series of GHRH-R antagonists, AVR, exhibits superior anticancer and anti-inflammatory activities in both in vivo and in vitro assays.

Elucidating the relationship between blood glucose dynamics and growth hormone responses in glucagon stimulation tests among children with short stature

Introduction: The use of glucagon as a provocative agent for growth hormone (GH) assessment is a cornerstone in pediatric endocrinology. Glucagon's role as a GH secretagogue is integral to growth hormone stimulation tests (GHSTs), which diagnose suspected GH deficiency (GHD) in children. These tests are crucial for assessing the hypothalamic-pituitary-adrenal (HPA) axis's integrity. Despite its prevalent use, the exact mechanisms by which glucagon prompts GH release and the impact of ensuing blood glucose (BG) fluctuations are not fully understood. Objectives: This study aims to explore the relationship between GH and BG levels in children with short stature following glucagon administration. Patients and Methods: A retrospective cohort study involved 42 pediatric patients, aged 6 to 11, with short stature. We analyzed GH and BG levels before and after intramuscular glucagon Simulation test (GST). Blood samples were taken at baseline and multiple intervals post-injection. Results: The results revealed that the mean glucose peaked at 60 minutes and declined to a nadir at 120 minutes, which corresponded with a significant rise in GH levels. GH concentrations peaked at 120 minutes post-injection, with 31% of children showing peak GH levels of less than 7 μg/L. Notably, the study found an inverse correlation between BG and GH at peak glucose times, suggesting a complex interplay between glucose dynamics and GH response. Discussion: Our findings indicate a dynamic interrelation between BG and GH post-glucagon injection, challenging traditional interpretations of GST results. The study reinforces the notion that GHST results should be interpreted with consideration of patient-specific factors such as BMI to ensure accurate evaluation of GH reserve and subsequent clinical decision-making. Conclusion: The study corroborates the dynamic nature of GH and glucose responses following glucagon administration and highlights the need for personalized approaches in interpreting GHSTs. Further investigation is warranted to elucidate the mechanisms influencing this complex relationship, which is crucial for accurate diagnosis and management of GHD in children.

GHRH and its analogues in central nervous system diseases.

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.

Characterization and Regulation of the Neonatal Growth Hormone Surge.

High neonatal growth hormone (GH) secretion has been described in several species. However, the neuroendocrine mechanisms behind this surge remain unknown. Thus, the pattern of postnatal GH secretion was investigated in mice and rats. Blood GH levels were very high on postnatal day (P)1 and progressively decreased until near zero by P17 in C57BL/6 mice without sex differences. This pattern was similar to that observed in rats, except that female rats showed higher GH levels on P1 than males. In comparison, follicle-stimulating hormone exhibited higher secretion in females during the first 3 weeks of life. Hypothalamic Sst mRNA and somatostatin neuroendocrine terminals in the median eminence were higher in P20/P21 mice than in newborns. Knockout mice for GH-releasing hormone (GHRH) receptor showed no GH surge, whereas knockdown mice for the Sst gene displayed increased neonatal GH peak. Leptin deficiency caused only minor effects on early-life GH secretion. GH receptor ablation in neurons or the entire body did not affect neonatal GH secretion, but the subsequent reduction in blood GH levels was attenuated or prevented by these genetic manipulations, respectively. This phenotype was also observed in knockout mice for the insulin-like growth factor-1 (IGF-1) receptor in GHRH neurons. Moreover, glucose-induced hyperglycemia overstimulated GH secretion in neonatal mice. In conclusion, GH surge in the first days of life is not regulated by negative feedback loops. However, neonatal GH secretion requires GHRH receptor, and is modulated by somatostatin and blood glucose levels, suggesting that this surge is controlled by hypothalamic-pituitary communication.

Synchronized long-term delivery of growth hormone and insulin-like growth factor 1 through poly (lactic-co-glycolic acid) nanoparticles on polycaprolactone scaffolds for enhanced osteochondral regeneration

The regeneration of osteochondral defects is challenging due to the complex structure of the osteochondral unit. This study aimed to develop a biomimetic scaffold by loading growth hormone (GH) and insulin-like growth factor-1 (IGF-1) into poly (lactic-co-glycolic acid) (PLGA) nanoparticles and incorporating them into polycaprolactone (PCL) scaffolds to promote synchronized osteochondral regeneration. The nanoparticles were successfully immobilized onto PCL scaffolds pre-modified with polydopamine (PDA) to enhance cell adhesion and proliferation. The scaffolds exhibited a sustained release of GH and IGF-1 over 30 days. In vitro studies using rabbit adipose-derived stem cells (ADSCs) showed that the GH/IGF-1 nanoparticle-loaded scaffolds (PCL/PDA/M-PLGA) significantly promoted cell proliferation, chondrogenic differentiation, and osteogenic differentiation compared to control PCL/PDA scaffolds. In vivo experiments using a rabbit osteochondral defect model revealed that the PCL/PDA/M-PLGA scaffolds facilitated superior osteochondral regeneration, evidenced by increased subchondral bone formation and cartilage matrix deposition. Overall, this study demonstrates the potential of GH/IGF-1 nanoparticle-loaded PCL scaffolds for synchronized osteochondral regeneration and provides a promising strategy for treating osteochondral defects.

GHRH-stimulated pituitary small extracellular vesicles inhibit hepatocyte proliferation and IGF-1 expression by its cargo miR-375-3p

Small extracellular vesicles (sEV) have emerged as a novel mode of intercellular material transport and information transmission. It has been suggested hormones may regulate the production and function of sEV. However, the specific impact of growth hormone-releasing hormone (GHRH) on pituitary sEV production and the role of sEV in the regulation of the GHRH-GH-IGF axis has not been previously reported. The results of the present study demonstrated that GHRH increased the production of pituitary sEV by promoting the expression of Rab27a. More importantly, GHRH induced alterations in protein and miRNA levels within GH3-sEV components. Notably, GH3-sEV with GHRH treatment exhibited the enhanced ability to impede BRL 3A cell proliferation and the expression of IGF-1. Conclusively, for the first time, we corroborate the influence of GHRH on pituitary sEV, thereby presenting novel evidence for how sEV participates in the balance of the GHRH-GH-IGF axis. Importantly, this study provides new insight into a novel balance mechanism mediated by sEV within the endocrine system.Graphical

Growth hormone-releasing hormone and cancer.

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.

A novel approach for the treatment of AML, through GHRH antagonism: MIA-602.

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.

Запальні захворювання кишечника: фокус на грелін

Today, diseases of the digestive organs remain one of the most urgent problems of modern medicine. Scientists pay considerable attention to the biochemical and molecular mechanisms underlying the development of these pathologies. In recent years, new hormones and neurotransmitters have been discovered that regulate energy metabolism and eating behavior, including ghrelin, a gastrointestinal hormone with various biological features and effects: it stimulates the release of growth hormone, stimulates appetite, has an anabolic effect, and affects carbohydrate metabolism. At the current stage, the biological effects of ghrelin are known, namely appetite regulation, anabolic effects, influence on the secretion of other hormones, and the work of the digestive system. The main expression of the hormone is concentrated in the stomach and decreases along the digestive tract. Patients with inflammatory bowel diseases are characterized by a high level of circulating ghrelin in the blood. Ghrelin protects the gut by reducing pro-inflammatory cytokine release and neutrophil infiltration. Ghrelin exerts an antioxidant effect by increasing the release of nitric oxide in the intestine. This paper describes the main physiological mechanisms of ghrelin action in the gastrointestinal tract

Acromegalia em felinos

Acromegaly in felines occurs mainly due to a pituitary adenoma of somatotropic cells, and presents slow and progressive evolution, responsible for increasing the production and secretion of growth hormones (GH). This condition is common in senile or adult male domestic cats, neutered and with short hair. The pathophysiology is due to the excessive release of GH in the adenohypophysis region, whose synthesis is regulated by growth hormone-releasing hormone (GHRH) and somatostatin, responsible for stimulating or inhibiting the secretory axis, respectively. The anabolic action of GH is responsible for increasing the secretion of IGF-1, which is mainly responsible for the clinical signs of acromegaly, such as body growth and organomegaly. The catabolic effect refers to insulin resistance. Clinical signs may be associated with secondary diabetes mellitus (DM), weight gain, exacerbated growth of various tissues and neurological signs as the tumor mass grows. The diagnosis of the disease can be performed through laboratory, imaging and endocrine tests such as the specific immunoassay for GH and/or insulin-like growth factor 1 (IGF-1). Treatment is based on controlling the DM that develops secondary to it, as well as on attempts to reduce or even inhibit the excess release of GH. Treatment can be performed with somatostatin analogues and dopamine agonists. The use of stereotactic radiotherapy can also be recommended, with favorable results for tumor reduction, as well as the surgical technique of transsphenoidal hypophysectomy, which presents better results than other techniques but is a complex surgical procedure. This project aims to inform veterinarians of this endocrine disease and its main currently recognized diagnoses and treatments, emphasizing the need to establish a differential diagnosis for difficult-to-control DM.

12533 A Rare Case of a Growth Hormone Releasing Hormone-Secreting Pulmonary Carcinoid Tumor: Clinical Presentation and Management

Abstract Disclosure: I. Yaseen: None. C. Woods: None. D.B. O'Shea: None. R.K. Crowley: None. D. O'Toole: None. H. Almeamar: None. We present a rare case of an ectopic Growth Hormone Releasing Hormone (GHRH)-secreting pulmonary neoplasm manifesting with acromegaly. A 62-year-old woman presented with Bell’s palsy. An incidental lung mass proved to be a 17.5cm carcinoid tumor, DOTATOC-avid, with bony and liver metastases, Ki67 1% on lung and bone biopsy. After pulmonary service referral to endocrinology, she was noted to have acromegalic features, the most troubling of which was macroglossia associated with mouth ulceration. IGF1 was 549ug/L (57-186), random growth hormone was 225. GHRH in serum was 1937ng/ml (reference < 60). MR Pituitary revealed hyperplasia.The multidisciplinary team discussion was that the lung lesion was unresectable, therefore she was commenced on somatuline autogel 120mg every 28 days and an opinion requested re suitability for Peptide Receptor Radionuclide Therapy. After 6 months of therapy IGF1 normalised to 90ug /L. GHRH reduced to 1056ng/L.Imaging at 8 months showed stability of lung primary and bone / liver metastases, with no benefit likely from PRRT at this time. This case highlights the importance of considering endocrine syndromes in the setting of a lung mass. The prevalence of acromegaly in Ireland is 69 per million people; this is the second Irish case known of GHRH-associated GH excess. Ectopic GH-secreting pulmonary tumors are a rare but important differential in patients presenting with acromegalic features. Complete surgical resection can be curative, underlining the significance of a multidisciplinary approach in management, encompassing endocrinology, thoracic surgery, and pathology. This case of successful medical management adds to the limited literature on such tumors and underscores the potential for non-pituitary neoplasms to cause systemic endocrinopathies. Presentation: 6/1/2024

Octreotide protects against LPS-induced endothelial cell and lung injury

Growth hormone (GH) is a crucial regulator of growth, cell reproduction, and regeneration; and it is controlled by growth hormone-releasing hormone (GHRH) and somatostatin. Lipopolysaccharides (LPS) can compromise endothelial function, leading to increased inflammation and vascular leak. Octreotide (OCT) is an FDA-approved synthetic somatostatin analog (SSA) used to treat acromegaly and neuroendocrine tumors. The present study investigates the effects of OCT on LPS-induced injury in bovine and human lung endothelial cells, as well as in mouse lungs. Our in vitro observations suggest that OCT effectively counteracts LPS-induced endothelial leak, inflammation, and reactive oxygen species (ROS) generation. Furthermore, OCT reduces bronchoalveolar lavage fluid (BALF) protein concentration in an experimental model of Acute Lung Injury (ALI). Our study suggests that OCT mitigates LPS-induced endothelial cell and lung injury, suggesting that it may represent an exciting therapeutic possibility in diseases related to barrier dysfunction.