Musculoskeletal Effects of Altered GH Action

Abstract

Growth hormone (GH) is a peptide hormone that can signal directly through its receptor or indirectly through insulin-like growth factor 1 (IGF-1) stimulation. GH draws its name from its anabolic effects on muscle and bone but also has distinct metabolic effects in multiple tissues. In addition to its metabolic and musculoskeletal effects, GH is closely associated with aging, with levels declining as individuals age but GH action negatively correlating with lifespan. GH’s effects have been studied in human conditions of GH alteration, such as acromegaly and Laron syndrome, and GH therapies have been suggested to combat aging-related musculoskeletal diseases, in part, because of the decline in GH levels with advanced age. While clinical data are inconclusive, animal models have been indispensable in understanding the underlying molecular mechanisms of GH action. This review will provide a brief overview of the musculoskeletal effects of GH, focusing on clinical and animal models.

Molecular characterization of physis tissue and hormonal profiles of female rats neonatally exposed to low-dose bisphenol A

“…One of the major functions of GH and IGF-1 is to promote linear growth. Our study indicated that BPA may have adverse effects on longitudinal growth according to its potential impact on the inhibition of GH level and stimulation of OC level, but GH level fluctuates with a well-defined rhythm (Wang et al, 2021), which can signal directly through its receptor or indirectly through IGF-1 stimulation (Young et al, 2022). However, only basal levels of hormones were measured in this study; therefore, may not be sensitive parameters and our results should be interpreted with caution.…”

“…Additionally, compared with traditional in vitro studies, the present study allowed us to visualize the gene expression in physis tissues from organisms exposed to BPA (Iskandarani et al, 2021). Since serum osteocalcin (OC) is a surrogate parameter of bone metabolism (Seidlová-Wuttke et al, 2004) and evidence indicates that growth hormone (GH) deficiency, partial GH insensitivity, and altered response to insulin-like growth factor 1 (IGF-1) could contribute to growth failure (Young et al, 2022), serum OC, GH, and IGF-1 levels were measured to evaluate the effects of BPA exposure on bone metabolism and growth potential.…”

Effects of 18 Months of Growth Hormone Replacement Therapy on Bone Mineral Density in Patients with Adult Growth Hormone Deficiency: A Retrospective Study

“…Unfortunately, we did not observe a correlation between IGF-1 levels and BMD at any time point. It may be due to the following reasons: (1) changes in serum IGF-1 are more sensitive to changes in BMD, with a signifcant increase in IGF-1 during the frst month of rhGH treatment, but the changes in BMD are relatively slow and complex, and the formation of new bone takes 6-12 months, so changes in BMD are not concordant with changes in serum IGF-1 levels [3,6]; (2) the duration of the disease varied in each subject, as did the duration of GH defciency, IGF-1, which can decrease markedly within a short time after onset, but the decrease in BMD lagged relatively behind; (3) changes in BMD are associated with various factors, such as serum 25-(OH)VD₃ levels, dietary habits, sunlight exposure, and exercise, and failure to use sex hormone replacement therapy in postmenopausal women can also interfere with BMD changes, as can previous hyperpituitarism in some patients with pituitary tumors [33]; (4) although GH acts mainly indirectly through IGF-1, in addition to that, GH can also act directly on bone [23]; (5) the analysis using only the values of IGF-1 did not exclude the interference of age on IGF-1, and the IGF-1 SD score for age should be widely used in the future clinical or scientifc research. We also found no correlation between peak GH and BMD or Z-scores, and when we grouped BMD and Z-scores according to peak GH, no diference was found between the groups.…”

“…Multiple studies have shown that replacement therapy with rhGH in patients with AGHD also produces some improvement in body composition and can reduce body fat mass (BFM), increase lean body mass [22,23], and enhance patient quality of life [18,24].…”

Sarcopenia and Endocrine Ageing: Are They Related?

“…As a result, the decrease in GH/IGF-1 contributes to muscle loss [ 24 ]. Enhancement in muscle strength and a shift in fiber types have been shown in certain trials of aged participants who receive GH therapy and resistance training [ 32 , 33 ].…”