BACKGROUND: Ultraviolet-B (UVB) radiation is the leading environmental cause of skin damage and photoaging. The epidermis and dermis layers of the skin mainly absorb UVB. UVB stimulates apoptosis, cell cycle arrest, generation of reactive oxygen species, and degradation of collagen and elastin fibers.
OBJECTIVE: This study investigated the potential of human growth hormone (hGH) in protecting the skin fibroblasts and keratinocytes (HFFF-2 and HaCaT cell lines) from UVB-induced damage.
METHODS: The MTT assay was performed to evaluate UVB-induced mitochondrial damage via assessing the mitochondrial dehydrogenase activity, and flow cytometry was carried out to investigate the effects of UVB and hGH on the cell cycle and apoptosis of UVB-irradiated cells. In addition, the fold change mRNA expression levels of Type I collagen and elastin in HFFF-2 cells were evaluated using the qRT-PCR method following UVB exposure.
RESULTS: We observed that treatment of cells with hGH before UVB exposure inhibited UVB-induced loss of mitochondrial dehydrogenase activity, apoptosis, and sub-G1 population formation in both cell lines. We also found that hGH-treated HFFF-2 cells showed up-regulated mRNA expression of Type I collagen, elastin, and IGF-1 in response to UVB irradiation.
CONCLUSIONS: These findings suggest hGH as a potential anti-UVB compound that can protect skin cells from UVB-induced damage. Our findings merit further investigation and can be used to better understand the role of hGH in skin photoaging.

Due to its involvement in skin maintenance and repair, topical administration of recombinant human growth hormone (rhGH) is an interesting strategy for therapeutic purposes. We have formulated and characterized a topical rhGH-loaded liposomal formulation (rhGH-Lip) and evaluated its safety, biological activity, and preventive role against UVB-induced skin damage. The rhGH-Lip had an average size and zeta potential of 63 nm and -33 mV, respectively, with 70 % encapsulation efficiency. The formulation was stable at 4 °C for at least one year. The SDS-PAGE and circular dichroism results showed no structural alterations in rhGH upon encapsulation. In vitro, studies in HaCaT, HFFF-2, and Ba/F3-rhGHR cell lines confirmed the safety and biological activity of rhGH-Lip. Franz diffusion cell study showed increased rhGH skin permeation compared to free rhGH. Animal studies in nude mice showed that liposomal rhGH prevented UVB-induced epidermal hyperplasia, angiogenesis, wrinkle formation, and collagen loss, as well as improving skin moisture. The results of this study show that rhGH-Lip is a stable, safe, and effective skin delivery system and has potential as an anti-wrinkle formulation for topical application. This study also provides a new method for the topical delivery of proteins and merits further investigation.

OBJECTIVE: Sweat glands and cutaneous vessels possess growth hormone (GH) and insulin-like growth factor 1 (IGF-1) receptors. Here, we assessed if exercise increases GH and IGF-1 in skin interstitial fluid, and whether baseline and exercise-induced increases in GH and IGF-1 concentrations in skin interstitial fluid/blood are associated with heat loss responses of sweating and cutaneous vasodilation.
METHODS: Sixteen young adults (7 women) performed a 50-min moderate-intensity exercise bout (50% VO2peak) during which skin dialysate and blood samples were collected. In a sub-study (n = 7, 4 women), we administered varying concentrations of GH (0.025-4000 ng/mL) and IGF-1 (0.000256-100 µg/mL) into skin interstitial fluid via intradermal microdialysis. Sweat rate (ventilated capsule) and cutaneous vascular conductance (CVC) were measured continuously for both studies.
RESULTS: Exercise increased sweating and CVC (both P < 0.001), paralleled by increases of serum GH and skin dialysate GH and IGF-1 (all P ≤ 0.041) without changes in serum IGF-1. Sweating was positively correlated with baseline dialysate and serum GH levels, as well as exercise-induced increases in serum GH and IGF-1 (all P ≤ 0.044). Increases in CVC were not correlated with any GH and IGF-1 variables. Exogenous administration of GH and IGF-1 did not modulate resting sweat rate and CVC.
CONCLUSIONS: (1) Exercise increases GH and IGF-1 levels in the skin interstitial fluid, (2) exercise-induced sweating is associated with baseline GH in skin interstitial fluid and blood, as well as exercise-induced increases in blood GH and IGF-1, and (3) cutaneous vasodilation during exercise is not associated with GH and IGF-1 in skin interstitial fluid and blood.

Genetic toxin-antitoxin element hok/sok from the natural Escherichia coli R1 plasmid ensures segregational stability of plasmids. Bacterial cells that have lost all copies of the plasmid encoding the short-lived antitoxin are killed by the stable toxin. When introduced into bacterial expression vectors, the hok/sok element can increase the productive time of recombinant protein biosynthesis by slowing down accumulation of non-producing cells lacking the expression plasmid. In this work, we studied the effects of position and orientation of the hok/sok element in the standard pET28a plasmid with the inducible T7lac promoter and kanamycin resistance gene. It was found that the hok/sok element retained its functional activity regardless of its location and orientation in the plasmid. Bacterial cells retained the hok/sok-containing plasmids after four days of cultivation without antibiotics, while the control plasmid without this element was lost. Using three target proteins - E. coli type II asparaginase (ASN), human growth hormone (HGH), and SARS-CoV-2 virus nucleoprotein (NP) - it was demonstrated that the maximum productivity of bacteria for the cytoplasmic proteins (HGH and NP) was observed only when the hok/sok element was placed upstream of the target gene promoter. In the case of periplasmic protein localization (ASN), the productivity of bacteria during cultivation with the antibiotic decreased for all variants of the hok/sok location. When the bacteria were cultivated without the antibiotic, the productivity was better preserved when the hok/sok element was located upstream of the target gene promoter. The use of the pEHU vector with the upstream location of the hok/sok element allowed to more than double the yield of HGH (produced as inclusion bodies) in the absence of antibiotic and to maintain ASN biosynthesis at the level of at least 10 mg/liter for four days during cultivation without antibiotics. The developed segregation-stabilized plasmid vectors can be used to obtain various recombinant proteins in E. coli cells without the use of antibiotics.

Pegvisomant, the first and currently only clinically available growth hormone receptor antagonist, is an effective therapeutic option for the medical treatment of acromegaly, a rare disorder characterized by excessive growth hormone secretion. With now over 20 years of real world experience, its safety and efficacy is well-established. However, several aspects of its clinical use are still controversially discussed. The high cost of pegvisomant has limited its use in several countries, and recent studies have reported a lower efficacy than the initial clinical trials. A reported increase in tumor volume under therapy varies between studies and has been attributed to either actual growth or re-expansion after cessation of somatostatin receptor ligand therapy. Furthermore, different combinations of pegvisomant and other therapeutic agents aiming at reduction of acromegaly disease activity have been proposed to increase or retain effectiveness while lowering side effects and cost. This review aims to assess current clinical data on the safety and efficacy of pegvisomant while also addressing controversies surrounding its use.

Growth hormone (GH) deficiency (GHD) is a rare disorder. The diagnosis of GHD requires a combination of two provocative GH tests. This study aimed to find agreement between commonly used medications to determine which combined tests have high reliability of agreement. This retrospective cohort included 201 children who underwent GH provocation testing from January 2012 to December 2022. The insulin tolerance test (ITT) with the clonidine stimulation test (CST) or glucagon stimulation test (GST) with the CST were performed. We calculated Cohen\'s kappa to determine the agreement between the test medications by considering the post-stimulation peak GH level with a cut-off value of 10 ng/mL as the primary outcome. A total of 151 patients underwent the two provocative tests and were included in the analysis. Of these patients, 119 underwent the ITT and CST and 54 (45.3%) were diagnosed with GHD. However, 32 patients underwent the GST and CST and 18 (56.2%) were diagnosed with GHD. The kappa value for ITT and CST was 0.258 (25.8%), indicating fair agreement between clonidine and insulin (p = 0.005). However, the kappa value for CST and GST was 0.178 (17.8%), representing slight agreement. The correlation coefficient revealed a very strong relationship between ITT and CST. Clonidine has fair agreement and a very strong correlation coefficient with ITT when used to diagnose GHD in children. Among the commonly used pharmacological tests for GH provocation in our unit, the CST was considered the best pharmacological test in terms of safety and reduced parental anxiety.

Dairy farm profitability depends on milk yield, so the dairy industry manages cows to improve their productivity. Both bovine somatotropin (bST) and early lactation increased milking frequency (IMF) and milk yield (MY) in dairy cows. The objective of this study was to evaluate the effects of mid-lactation bST administration on milk production in established lactation when combined with the milk yield carry-over effect from early lactation IMF. Thirteen multiparous Holstein cows were milked unilaterally for 20 days in early lactation. The left udder halves were milked twice daily (2X) and the right udder halves were milked four times daily (4X). Udder halves milked 4X produced 8.60 ± 1.40 kg more than 2X on the final day of IMF treatment. Cows were then returned to 2X milking for the remainder of lactation and sampled on alternate days from 74-94 days in milk (DIM). Bovine somatotropin was administered to all cows at 80 DIM. The 4X halves continued to make 2.66 ± 0.12 kg/d more milk than 2X through 94 DIM. Fat, protein, and lactose yields were significantly greater in the 4X halves compared to the 2X from 74-94 DIM. Overall milk yield increased by 2.71 kg/d with bST administration. However, there was no significant interaction between MF and bST administration. We can infer from these data that the mechanisms by which bST and IMF in early lactation increase milk yield are complementary due to their non-synergistic nature of enhancing MY.

Recombinant human growth hormone (rhGH) is a therapeutic protein, associated with various human diseases, such as growth hormone deficiency. One of the interesting issues in the formulation of therapeutic proteins is excipients like disaccharides. In the current study, we try to compare the effect of sucrose and trehalose on the structure of rhGH in the liquid state at 25°C and 55°C. We use spectroscopic techniques including intrinsic and extrinsic fluorescence, Fourier-transform infrared (FTIR), circular dichroism (CD), dynamic light scattering (DLS), and time-resolved fluorescence. FTIR shows a slight change in the secondary structure of rhGH in presence of the sugars as sucrose is more effective than trehalose. Fluorescence investigations also confirm the enhancements of folding of rhGH and fluorescein isothiocyanate (FITC)-rhGH in presence of sucrose (1.5-fold more than trehalose). Also, we studied sucrose\'s effect on the rete of aggregation of rhGH using spectroscopy of Congo red, and fluorescence imaging of thioflavin T (ThT)-treated samples. It can be suggested that sucrose facilitates the amyloid formation of rhGH during 20 days of incubation at 37°C. This study will help to understand the growth hormone structural behavior in the liquid state in the presence of sucrose and trehalose in vitro.

Neonatal maturity depends on the maternal capacity to provide nutrients for foetal growth. This study aimed to investigate the effects of systemic administration of recombinant porcine somatotropin (pST), one of the main regulators of growth and metabolism, to pregnant gilts during late gestation on circulating nutrients and expression levels of genes in liver and skeletal muscle of their 110-day-old foetuses. Gilts received either daily injections of sterile water (control [CTL] group, n = 15) or of 5 mg of pST (pST group, n = 17) from days 90 to 109 of gestation. At day 110 postconceptus, pairs of foetuses (one of small and one of average size within a litter) were selected. Circulating fructose concentrations were greater, but circulating concentrations of urea were lower in pST than in CTL foetuses. Expression levels of genes involved in carbohydrate and lipid metabolism were more affected by pST treatment in liver than in muscle. Hepatic molecular changes suggest an inhibition of energy-consuming processes (glycogen and lipid biosynthesis) and the activation of energy-producing pathway (mitochondrial oxidation) in pST compared to CTL foetuses. Expression levels of some genes involved in intracellular degradation of proteins were greater in the liver of pST foetuses, and combined with lower uremia, this suggests a higher utilisation of protein sources in pST foetuses than in CTL foetuses. In muscle, molecular changes were mainly observed in the IGF-insulin axis. Altogether, pST-treated gilts seem to have a greater ability to support foetal liver development by the reorientation of energy and protein metabolism.

COVID-19 is a worldwide pandemic caused by SARS-CoV-2, to which adults are usually more susceptible than children. Growth hormone (GH) levels differ between children and adults and decrease with age. There is bidirectional crosstalk between the GH/insulin-like growth factor-1 (IGF-1) pathway and the immune system that plays a significant role in SARS-CoV-2 infection. We evaluated the association between somatotropin treatment (GH replacement therapy) and the risk for SARS-CoV-2 positivity (a marker for COVID-19 infection) in children with growth hormone issues (GHI): growth hormone deficiency (GHD) and idiopathic short stature (ISS). A population-based cross-sectional study in Leumit Health Services (LHS) was performed using the electronic health record (EHR) database. The rates of SARS-CoV-2 positivity were evaluated among children with GHI, treated or untreated with somatotropin. Higher rates of SARS-CoV-2 positivity were found in GHI children, influenced by the same confounders reported in the pediatric population. A lower prevalence of SARS-CoV-2 PCR positivity was found among the somatotropin-treated children. A multivariate analysis documented that somatotropin treatment was associated with a reduced risk of SARS-CoV-2 positivity (Odds Ratio (OR) = 0.47, Confidence Interval (CI) 0.24-0.94, p = 0.032). Thus, somatotropin might be a protective factor against SARS-CoV-2 infections, possibly related to its immunomodulatory activity.