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Open research questions in Growth Hormone and Insulin-like Growth Factors

44 unresolved questions extracted from the limitations and future-work sections of 219 Growth Hormone and Insulin-like Growth Factors papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Higher circulating levels of IGFBP-1 and IGFBP-2 have been established as markers of protection from incident type 2 diabetes, yet their associations with cardiovascular disease remain unclear.

    Discordant associations of IGF-binding proteins 1 & 2 with diabetes and cardiovascular disease: insights from UK Biobank · 2026 · DOI

  • Recent studies have shown that adipose (pro)renin receptor ([P]RR) may play a role in fat accumulation, and we previously reported increased adipose (P)RR expression in growth hormone (GH) deficiency in mice; however, the association between human adipose (P)RR expression and GH deficiency remains unclear.

    Association between adipose (pro)renin receptor expression and growth hormone deficiency in patients with non-functioning hypothalamic-pituitary masses · 2026 · DOI

  • Strengths and limitations This study provides a detailed phenotypic characterization and relatively long-term follow-up of growth-promoting therapy in a rare cohort of patients with FBN1-related AD/GD2.

    FBN1 TB5 domain variants in acromelic dysplasia: multisystem manifestations, genotype–phenotype correlations, and partial responses to growth hormone therapy · 2026 · DOI

  • While IGFL1 has been increasingly recognized as a biomarker in several tumor types as well as in inflammatory diseases [22–26], little is known about its exact function.

    Enhanced IGFL1 translation in response to IL-1β is controlled by distinct 3’UTR elements · 2026 · DOI

  • The strength of this study was that it was conducted within a large cohort of the general population in Japan, where the incidence of hemorrhagic stroke is relatively high. Our study was based on systematic surveillance for incident stroke and employed standardized epidemiological methods for measuring biomarkers. This study has several potential limitations. First, only single-point measurements of biomarkers and risk factors at baseline were available, which could lead to regression dilution bias. Second, statistical power was limited, particu- larly in subtype analyses (SAH and ICH), location-specific analyses (deep and lobar ICH), and tertile-based analyses; therefore, these findings should be interpreted with caution. Nevertheless, these analyses may still provide meaning- ful insights into the association between IGF-I and hem- orrhagic stroke, and possibly its underlying mechanisms. Third, although we adjusted for potential confounders, we cannot rule out residual confounding from unmeasured fac- tors, such as antithrombotic medication use, which was not available in this study. Fourth, the study population was limited to Japanese residents, so generalizability should be considered with caution. Nevertheless, because biomarkers and risk factors for hemorrhagic stroke may be common across racial and ethnic groups, the evidence may pro- vide a basis for extrapolation to other populations. Lastly, we used frozen serum samples to estimate sFas and IGF-I and did not examine long-term changes in the samples. A previous report showed that these biomarkers remained stable in serum samples stored for up to nine years at -70 °C in another Japanese cohort, where sample management methods were nearly identical to those in our study [32]. 1 3Translational Stroke Research (2026) 17:57 57 Page 6 of 7 As additional analyses stratified by storage duration yielded similar results, it is unlikely that long-term storage affected the findings.

    Associations of Blood Soluble Fas and IGF-I with Risk of Hemorrhagic Stroke: The Circulatory Risk Communities Study (CIRCS) · 2026 · DOI

  • Research over the past decade has established IGFBP2 as a pleiotropic regulator modulating glucose and lipid homeostasis in a tissue-specific and context-dependent manner. This review highlights the intricate signaling networks through which IGFBP2 acts across metabolic tissues, including EGFR-STAT3 signaling in the liver, integrin-dependent pathways in adipose and vascular contexts, and insulin-responsive signaling in skeletal muscle, with possible additional links to AMPK-related mechanisms. In addition, emerging evidence suggests that IGFBP2 is responsive to nutritional status, weight-loss interventions, and broader metabolic remodeling, supporting its role as a nutrition-sensitive component of metabolic regulation. However, its eects, particularly in adipose tissue and the cardiovascular system, remain highly context- dependent, ranging from metabolically protective associations in some settings to potential links with pathological remodeling or adverse vascular phenotypes in others. A major challenge lies in deciphering the molecular determinants, including post- translational modifications and tissue microenvironmental cues, that govern these divergent outcomes.

    Tissue-specific roles of IGFBP2 in glucose and lipid metabolism in obesity-related metabolic diseases · 2026 · DOI

  • Most studies to date have been conducted in vitro, and direct evidence from animal models linking IGFBP-6 to redox-modulated fibrotic or oncogenic phenotypes is limited.

    Redox Biology and Insulin-like Growth Factor-Binding Protein-6: A Potential Relationship · 2025 · DOI

  • The literature offers no reports on the presence and role of IGF-1 isoforms in the ovaryThe aim of the study was to assess the IGF-1A, B and C isoforms at the level of IGF-1 gene transcription in the ovaries of PCOS women and healthy controls.

    Insulin-like growth factor-1 isoforms in human ovary. Preliminary report on the expression of the IGF-1 gene in PCOS patients and healthy controls. · 2015 · DOI

  • Additionally, the treatment of GHD remains a source of much debate; there is no consensus on the best mechanism for determining the starting dose of GH in patients with GHD.

    Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence · 2015 · DOI

  • This study demonstrated that both age and gender account for variations in specific GFs present in PRP, and this may partially explain some of the inconsistent results of PRP clinical trials.

    Gender and Age Differences in Growth Factor Concentrations From Platelet-Rich Plasma in Adults · 2014 · DOI

  • Future research should focus on establishing criteria for when imaging is necessary, determining the optimal timing and dosage of dopamine agonists for BH₄ deficiency, and evaluating the long-term outcomes of treated versus untreated prolactinoma in this population.

    Prolactinoma Associated with L-Dopa–Resistant Hyperprolactinemia in a Child with Tetrahydropterin (BH4) Deficiency · 2026 · DOI

  • Further studies in larger populations are warranted to better elucidate the role of FGF21 in glucose metabolism and its secretion profile.

    2465-P: FGF21 Is Related to Insulin Secretion during OGTT in Patients with High MASLD Probability: Preliminary Data from a Human Cohort · 2026 · DOI

  • The contribution of apoptosis is well established in athero- sclerosis but remains unclear in hypertensive arterioloscle- rosis [25].

    Associations of Blood Soluble Fas and IGF-I with Risk of Hemorrhagic Stroke: The Circulatory Risk Communities Study (CIRCS) · 2026 · DOI

  • Current prolactin testing recommendations in obese individuals are based primarily on clinical experience and observational research evidence, requiring further validation.

    From the perspective of prolactin: a view on obesity · 2026 · DOI

  • Future research should integrate longitudinal population studies, mechanistic experiments, and circadian rhythm assessments to determine whether prolactin should be considered a driver, regulator, or biomarker of obesity-related metabolic disorders.

    From the perspective of prolactin: a view on obesity · 2026 · DOI

  • The quantitative contribution of extrapituitary prolactin in adipose tissue and immune cells to circulating prolactin levels and its functional significance in human metabolic regulation remain unclear.

    From the perspective of prolactin: a view on obesity · 2026 · DOI

  • Whether an optimal physiological prolactin range is conducive for maintaining energy balance and glucose homeostasis remains largely based on observational and experimental evidence, with limited research and definitive conclusions.

    From the perspective of prolactin: a view on obesity · 2026 · DOI

  • Future human studies combining time-series hormone monitoring are urgently needed to elucidate the role of prolactin rhythm dynamics in metabolic regulation and its potential clinical value.

    From the perspective of prolactin: a view on obesity · 2026 · DOI

  • Whether interventions targeting the prolactin circadian rhythm (such as behavioral modifications, time-based therapy, or pharmacological interventions) can bring about metabolic benefits remains speculative.

    From the perspective of prolactin: a view on obesity · 2026 · DOI

  • Direct causal evidence in humans regarding prolactin circadian rhythm's role in fat accumulation and metabolic abnormalities remains limited, as current hypotheses are based on experimental studies and cross-species comparative data.

    From the perspective of prolactin: a view on obesity · 2026 · DOI

  • These findings suggest that low-dose rhGH may offer therapeutic potential for sarcopenic obesity, warranting further investigation in larger, longer-term studies.

    Effects of low-dose growth hormone treatment on obesity: a meta-analysis of randomized controlled trials · 2025 · DOI

  • The exact explanation for the positive response to rhGH treatment without the expected increase in IGF1 in our patient remains unknown.

    Is growth without IGF1 possible? A case report · 2017 · DOI

  • However, only a few data indicate the role of prolactin in psoriatic arthritis (PsA), whose etiology and disease progression are not fully elucidated, and the diagnosis is very difficult.

    Prolactin as an immunomodulatory factor in psoriatic arthritis · 2013 · DOI

  • However, detailed systematic studies of the cultural diffusion of this drug (including the motivations for use, prevalence, patterns of use, and supply network) are lacking.

    Injecting human growth hormone as a performance-enhancing drug—perspectives from the United Kingdom · 2009 · DOI

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44 open questions have been extracted from the limitations and future-work passages of 219 Growth Hormone and Insulin-like Growth Factors papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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