-
Archives of Endocrinology and Metabolism 2019The somatotropic axis is the main hormonal regulator of growth. Growth hormone (GH), also known as somatotropin, and insulin-like growth factor 1 (IGF-1) are the key... (Review)
Review
The somatotropic axis is the main hormonal regulator of growth. Growth hormone (GH), also known as somatotropin, and insulin-like growth factor 1 (IGF-1) are the key components of the somatotropic axis. This axis has been studied for a long time and the knowledge of how some molecules could promote or impair hormones production and action has been growing over the last decade. The enhancement of large-scale sequencing techniques has expanded the spectrum of known genes and several other candidate genes that could affect the GH-IGF1-bone pathway. To date, defects in more than forty genes were associated with an impairment of the somatotropic axis. These defects can affect from the secretion of GH to the bioavailability and action of IGF-1. Affected patients present a large heterogeneous group of conditions associated with growth retardation. In this review, we focus on the description of the GH-IGF axis genetic defects reported in the last decade. Arch Endocrinol Metab. 2019;63(6):608-17.
Topics: Genotype; Growth Disorders; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Mutation; Phenotype; Signal Transduction
PubMed: 31939486
DOI: 10.20945/2359-3997000000191 -
Growth Hormone & IGF Research :... 2023Patients with Noonan syndrome typically have a target height <2 standard deviations compared to the general population, and half of the affected adults remain... (Review)
Review
Patients with Noonan syndrome typically have a target height <2 standard deviations compared to the general population, and half of the affected adults remain permanently below the 3rd centile for height, though their short stature might result from a multifactorial etiology, not-yet fully understood. The secretion of growth hormone (GH) following the classic GH stimulation tests is often normal, with baseline insulin-like growth factor-1 (IGF-1) levels at the lower normal limits, but patients with Noonan syndrome have also a possible moderate response to GH therapy, leading to a final increased height and substantial improvement in growth rate. Aim of this review was to evaluate both safety and efficacy of GH therapy in children and adolescents with Noonan syndrome, also evaluating as a secondary aim the possible correlations between the underlying genetic mutations and GH responses.
Topics: Adolescent; Humans; Child; Growth Hormone; Noonan Syndrome; Human Growth Hormone; Insulin-Like Growth Factor I; Growth Disorders; Mutation; Body Height
PubMed: 37084633
DOI: 10.1016/j.ghir.2023.101532 -
Nature Reviews. Endocrinology Jun 2022Growth hormone (GH) and insulin-like growth factor 1 (IGF1) are important regulators of bone remodelling and metabolism and have an essential role in the achievement and... (Review)
Review
Growth hormone (GH) and insulin-like growth factor 1 (IGF1) are important regulators of bone remodelling and metabolism and have an essential role in the achievement and maintenance of bone mass throughout life. Evidence from animal models and human diseases shows that both GH deficiency (GHD) and excess are associated with changes in bone remodelling and cause profound alterations in bone microstructure. The consequence is an increased risk of fractures in individuals with GHD or acromegaly, a condition of GH excess. In addition, functional perturbations of the GH-IGF1 axis, encountered in individuals with anorexia nervosa and during ageing, result in skeletal fragility and osteoporosis. The effect of interventions used to treat GHD and acromegaly on the skeleton is variable and dependent on the duration of the disease, the pre-existing skeletal state, coexistent hormone alterations (such as those occurring in hypogonadism) and length of therapy. This variability could also reflect the irreversibility of the skeletal structural defect occurring during alterations of the GH-IGF1 axis. Moreover, the effects of the treatment of GHD and acromegaly on locally produced IGF1 and IGF binding proteins are uncertain and in need of further study. This Review highlights the pathophysiological, clinical and therapeutic aspects of skeletal fragility associated with perturbations in the GH-IGF1 axis.
Topics: Acromegaly; Animals; Dwarfism, Pituitary; Growth Hormone; Human Growth Hormone; Humans; Insulin-Like Growth Factor I
PubMed: 35288658
DOI: 10.1038/s41574-022-00649-8 -
Endocrine-related Cancer Sep 2023Despite landmark advances in cancer treatments over the last 20 years, cancer remains the second highest cause of death worldwide, much ascribed to intrinsic and... (Review)
Review
Despite landmark advances in cancer treatments over the last 20 years, cancer remains the second highest cause of death worldwide, much ascribed to intrinsic and acquired resistance to the available therapeutic options. In this review, we address this impending issue, by focusing the spotlight on the rapidly emerging role of growth hormone action mediated by two intimately related tumoral growth factors - growth hormone (GH) and insulin-like growth factor 1 (IGF1). Here, we not only catalog the scientific evidences relating specifically to cancer therapy resistance inflicted by GH and IGF1 but also discuss the pitfalls, merits, outstanding questions and the future need of exploiting GH-IGF1 inhibition to tackle cancer treatment successfully.
Topics: Humans; Human Growth Hormone; Insulin-Like Growth Factor I; Neoplasms; Growth Hormone
PubMed: 37283510
DOI: 10.1530/ERC-22-0414 -
Frontiers in Endocrinology 2022Growth hormone (GH) is mainly secreted by eosinophils of anterior pituitary gland. GH plays an important role in regulating the growth and development of many tissues... (Review)
Review
Growth hormone (GH) is mainly secreted by eosinophils of anterior pituitary gland. GH plays an important role in regulating the growth and development of many tissues and cells, so it is used in the treatment of many diseases. In recent years, the regulation of GH on ovarian function has attracted much attention. GH has been applied in controlled ovarian hyperstimulation, particularly in the patients with advanced age, diminished ovarian reserve (DOR) and poor ovarian response (POR). GH can directly bind to the growth hormone receptor (GHR) on the ovary to promote the growth, maturation and ovulation of follicles, as well as to inhibit follicular atresia. GH so as to promote the occurrence of early follicles, enhance the sensitivity of follicles to gonadotropins, accelerate the maturation of oocyte nucleus, improve mitochondrial activity and the quality of oocytes through the insulin-like growth factor (IGF) system, which is an indirect regulation. The deep-seated effects of GH on human reproduction and ovarian aging need further basic research and clinical practice.
Topics: Female; Humans; Growth Hormone; Ovary; Follicular Atresia; Human Growth Hormone; Aging
PubMed: 36699044
DOI: 10.3389/fendo.2022.1072313 -
Protein and Peptide Letters 2020Biological markers (biomarkers) play a key role in drug development, regulatory approval and clinical care of patients and are linked to clinical and surrogate outcomes.... (Review)
Review
Biological markers (biomarkers) play a key role in drug development, regulatory approval and clinical care of patients and are linked to clinical and surrogate outcomes. Both acromegaly and Growth Hormone Deficiency (GHD) are pathological conditions related to important comorbidities that, in addition to having stringent diagnostic criteria, require valid markers for the definition of treatment, treatment monitoring and follow-up. GH and insulin-like growth factor-I (IGF-I) are the main biomarkers of GH action in children and adults while, in acromegaly, both GH and IGF-I are established biomarkers of disease activity. However, although GH and IGF-I are widely validated biomarkers of GHD and acromegaly, their role is not completely exhaustive or suitable for clinical classification and follow-up. Therefore, new biological markers for acromegaly and GH replacement therapy are strongly needed. The aim of this paper is to review and summarize the current state in the field pointing out new potential biomarkers for acromegaly and GH use/abuse.
Topics: Acromegaly; Adult; Biomarkers; Child; Female; Hormone Replacement Therapy; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male
PubMed: 32310036
DOI: 10.2174/0929866527666200420103816 -
Frontiers in Endocrinology 2024
Topics: Humans; Dwarfism; Human Growth Hormone
PubMed: 38606084
DOI: 10.3389/fendo.2024.1403112 -
International Journal of Molecular... Jun 2023Congenital growth hormone deficiency (GHD) is a rare disease caused by disorders affecting the morphogenesis and function of the pituitary gland. It is sometimes found... (Review)
Review
Congenital growth hormone deficiency (GHD) is a rare disease caused by disorders affecting the morphogenesis and function of the pituitary gland. It is sometimes found in isolation but is more frequently associated with multiple pituitary hormone deficiency. In some cases, GHD may have a genetic basis. The many clinical signs and symptoms include hypoglycaemia, neonatal cholestasis and micropenis. Diagnosis should be made by laboratory analyses of the growth hormone and other pituitary hormones, rather than by cranial imaging with magnetic resonance imaging. When diagnosis is confirmed, hormone replacement should be initiated. Early GH replacement therapy leads to more positive outcomes, including reduced hypoglycaemia, growth recovery, metabolic asset, and neurodevelopmental improvements.
Topics: Infant, Newborn; Humans; Hypopituitarism; Human Growth Hormone; Pituitary Hormones; Growth Hormone; Hypoglycemia
PubMed: 37373261
DOI: 10.3390/ijms241210114 -
Endocrine-related Cancer Jan 2024It is now apparent that growth hormone (GH), an anterior pituitary hormone predominantly regulating postnatal somatic growth and metabolism, is also expressed in... (Review)
Review
It is now apparent that growth hormone (GH), an anterior pituitary hormone predominantly regulating postnatal somatic growth and metabolism, is also expressed in extrapituitary tissues. An extrapituitary synthetic site of GH that has garnered interest is the de novo or enhanced expression of GH in carcinoma or other cancers. In a number of cancers, including carcinoma of the mammary gland, endometrium, liver, prostate, and colon, the expression of GH is independently associated with more advanced clinicopathologic parameters of the cancer. In some of these cancers, tumor human growth hormone (hGH) expression portends worse survival outcomes for patients. Functionally, tumor-derived hGH exerts both autocrine and paracrine functions on carcinoma cells and cancer-associated stroma. Expression of autocrine/paracrine hGH in cancer drives tumor growth, angiogenesis, metastasis, and resistance to therapy by promotion of cancer cell proliferation, survival, epithelial-to-mesenchymal transition, motility, invasion, cancer stem cell-like behavior, and metastasis. Autocrine/paracrine hGH activates oncogenic signaling pathways and specific transcriptome signatures and enhances the expression of an oncogenic secretome to promote these functions. Hence, extrapituitary expression of GH in cancer promotes cancer progression independent of endocrine hGH, and may be considered as a validated target in oncology.
Topics: Humans; Carcinoma; Epithelial-Mesenchymal Transition; Growth Hormone; Human Growth Hormone
PubMed: 37877767
DOI: 10.1530/ERC-23-0120 -
Growth Hormone & IGF Research :... 2019This brief review highlights new studies in three areas of the GH field, namely diagnostics, therapeutics and biomarkers. The diagnosis of GH deficiency has always... (Review)
Review
This brief review highlights new studies in three areas of the GH field, namely diagnostics, therapeutics and biomarkers. The diagnosis of GH deficiency has always presented a challenge: there is no "gold standard" test of GH status, and GH levels during stimulation testing are affected by many factors that limit diagnostic accuracy. Two new approaches to diagnosis have been proposed: one involves a classical endocrine test of GH production using a GH secretagogue to test the Ghrelin axis, and shows promise in the diagnosis of adult GH deficiency. The other uses a completely different approach analysing the individual's gene expression profile as a surrogate for GH status with high levels of test accuracy. From the therapeutic aspect, there have been significant efforts to produce a long-acting (LA) GH on the premise that this will improve adherence and patient convenience. Aspects of LA-GH pharmacology are considered, and it will be interesting to see in future years what place LA-GH GH takes in the market. Long term surveillance is a vital part of therapeutics; recent studies across Europe have provided reassurance on the safety of recombinant human GH (r-hGH) for those with uncomplicated growth disorders, but do emphasise the need to continue observation through adulthood. The search for biomarkers that precisely reflect GH action in children and adults is an ongoing task. One of the newer bone markers that shows promise is a fragment of collagen type X which now requires further investigation in humans. In parallel with the diagnostic studies, gene expression profiles at the start of r-hGH treatment have been used to predict GH response in children with GHD and girls with Turner syndrome. These data are promising but need evaluation across a range of growth disorders. R-hGH is an effective, safe therapy used in both children and adults. There is however a need to continue to refine diagnosis, treatment and most importantly long-term pharmacovigilance to ensure that the right patients have the best treatment with robust safety profiles.
Topics: Growth Disorders; Human Growth Hormone; Humans; Time Factors
PubMed: 31706073
DOI: 10.1016/j.ghir.2019.10.003