Recombinant Growth Hormone Research Articles

Osteometabolic profile and bone mass in the transition phase: ethnic differences in Brazilians treated with somatropin during childhood

ObjectiveThe main growth hormone action is to promote linear growth increasing protein synthesis stimulation and osteoblastic activity. Peak bone mass extends from adolescence to 30 years of age. Several factors may influence this acquisition and prevent fracture risk in adulthood, such as genetic potential, GH, ethnicity, and lifestyle factors. This study aims to compare bone mass and osteometabolic profile of white and Afro-descendant Brazilian adolescents in the transition phase, who were treated with human recombinant growth hormone in childhood. MethodsThe authors selected 38 adolescents from the Transition Outpatient Clinic of the University of São Paulo. Lumbar spine and total body bone mineral density (BMD) and bone mineral content (BMC), serum calcium, 25-OH-vitamin D and bone markers were analyzed at the rhGH withdrawal. ResultsThe mean age was 16.8 ± 1.6 years. There were 21 Afro-descendant and 17 whites. Thirty-four percent of the sample presented vitamin D insufficiency, 66% inadequate calcium intake and 44.7% physical inactivity. The Afro-descendants showed a lower lumbar spine and total body Z scores than those of the whites (p = 0.04 and p = 0.03, respectively), as well as their mean body weight (p = 0.03). There were no differences in the remaining osteometabolic parameters. ConclusionAs most adolescents had vitamin D insufficiency, low calcium intake, and physical inactivity, calcium, and cholecalciferol supplementation and lifestyle changes should be encouraged. The Brazilian Afro-descendant may be a vulnerable group for low bone mass, requiring special strategies to increase bone accrual and body weight. More studies are necessary to compare ethnic differences in this population.

Recombinant growth hormone therapy for cystic fibrosis in children and young adults

Recombinant growth hormone therapy for cystic fibrosis in children and young adults

Recombinant growth hormone therapy for X-linked hypophosphatemia in children

Recombinant growth hormone therapy for X-linked hypophosphatemia in children

Impact of Antioxidant Feed and Growth Manipulation on the Redox Regulation of Atlantic Salmon Smolts.

Accumulating evidence indicates a close relationship between oxidative stress and growth rate in fish. However, the underlying mechanisms of this relationship remain unclear. This study evaluated the combined effect of dietary antioxidants and growth hormone (GH) on the liver and the muscle redox status of Atlantic salmon. There were two sequential experimental phases (EP) termed EP1 and EP2, each lasting for 6 weeks. In EP1, Atlantic salmon were fed either low-(L, 230 mg/kg ascorbic acid (Asc), 120 mg/kg α-tocopherol (α-TOH)), or high-(H, 380 mg/kg Asc, 210 mg/kg α-TOH)vitamin diets. The vitamins were supplemented as stable forms and the feeding was continued in EP2. In EP2, half of the fish were implanted with 3 μL per g body weight of recombinant bovine GH (Posilac®, 1 mg rbGH g BW−1) suspended in sesame oil, while the other half were held in different tanks and sham-implanted with similar volumes of the sesame oil vehicle. Here, we show that increasing high levels of vitamin C and E (diet H) increased their content in muscle and liver during EP1. GH implantation decreased vitamin C and E levels in both liver and muscle but increased malondialdehyde (MDA) levels only in the liver. GH also affected many genes and pathways of antioxidant enzymes and the redox balance. Among the most consistent were the upregulation of genes coding for the NADPH oxidase family (NOXs) and downregulation of the oxidative stress response transcription factor, nuclear factor-erythroid 2-related factor 2 (nrf2), and its downstream target genes in the liver. We verified that GH increases the growth rate until the end of the trail and induces an oxidative effect in the liver and muscle of Atlantic salmon. Dietary antioxidants do lower oxidative stress but have no effect on the growth rate. The present study is intended as a starting point to understand the potential interactions between growth and redox signaling in fish.

Application of recombinant Growth Hormone (rGH) in formulated Feed on Growth of Asian Seabass Lates calcarifer

This study aimed to gain rGH dose for the growth of Asian Seabass This research was conducted from July to September 2020 in Madong Village, Tanjungpinang City, Riau Islands Province. The method used was a completely randomized design (CRD) with 4 treatments and 3 replications, namely K: without rGH, A: 10 mg rGH / kg of feed, B: 12 ​​mg of rGH / kg of feed and C: 14 mg of rGH / kg of feed. The results of the absolute weight parameter study showed the values ​​of K (24.79 ± 3.13 g), A (23.87 ± 1.91 g), B (42.01 ± 1.87 g) and C (41.93 ± 0.99 g). The daily growth rate parameters indicated the values ​​of K (0.59 ± 0.07 g), A (0.57 ± 0.05 g), B (1.00 ± 0.04 g) and C (1.00 ± 0.02 g). This study concludes that the rGH affects the growth of Asian Seabass seed. It can be seen from the best treatment namely the treatment with a dose of rGH 12 mg/kg of feed with an absolute weight parameter value of 42.01 ± 1.87 g and a daily growth rate of 1.00 ± 0.04 g / day.

Compliance to Growth Hormone Therapy in Children and Adolescents with Growth Hormone Deficiency and Turner Syndrome and Impact on Height Velocity: A Prospective Study

Adherence to recombinant growth hormone (rGH) in children is necessary to ensure good treatment outcome. Reported non-compliance to rGH in children varied from 5-82% with little data involving Asian population. The objectives of this study are to evaluate the compliance of children and adolescents to rGH, effect of non-compliance on growth and factors affecting non-adherence. Methods: This is a prospective cohort study over 1-year aiming at all patients age less than 18 years old treated with rGH in our centre. Compliance was assessed from the number of returned medications and electronic record within device. Poor compliance was defined as utilised dose <86% prescribed (equivalent to missing injection ≥1 per week). Result: Thirty-four patients were recruited including 20 (59%) patients with GH deficiency and 14 (41%) with Turner syndrome. Poor compliance was noted in 35% of patients. Poor compliance in GHD patients was significantly associated with an older age (mean 12.55 ± 3.33 vs 9.28 ± 3.20 years old, p=0.038) and longer duration of treatment (mean 5.41 ± 3.0 vs 2.93 ± 2.18 years, p=0.046). Frequent reasons for missing doses were forgetfulness and inadequate medications. Participants with poor compliance had significantly reduced height velocity (HV) and HV standard deviation score (SDS) compared to those with good compliance (p<0.05). Conclusion: Poor compliance is more common in adolescents, those on longer duration of treatment and leads to significantly reduced height velocity. Regular monitoring throughout the course of rGH is important. Measures to improve compliance must address the underlying reasons.

Detection of prohibited growth factors (GFs) in doping control: serum concentration ranges in a reference population of athletes

Growth factors (GFs) are a wide class of polypeptides that can regulate cellular proliferation, migration and differentiation. Due to their ability to extensively impact on tissue regeneration, the use of GFs in sports is currently prohibited in and out of competition and included in the 2022 List of Prohibited Substances of the World Anti‐Doping Agency (WADA). At present, methods of detection of prohibited GFs for doping control purposes have been developed exclusively for recombinant Growth Hormone (recGH) and Insulin‐like growth factor1 (IGF‐1).Since GFs are endogenously produced substances, their abuse can be detected by fixing “reporting threshold” to differentiate their normal, physiological levels and the exogenous administration. Such a strategy imposes the determination of “normality ranges” for the athletic population.We considered the principal banned GFs, that are fibroblast growth factor (FGF), platelet‐derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF), measuring their levels – including those of their major isoforms – in 92 serum samples, collected from elite athletes in the framework of doping control tests. Preliminarily, we confirmed all the above considered growth factors are actually measurable in serum, defining also their respective limits of detection. Furthermore, we were able to identify differences in concentration levels possibly related to gender and age. Finally, we established normal serum concentration ranges, that can be used as reference normal population values necessary to fix threshold values able to discriminate the physiological levels and the recourse of doping practices.

Increased testicular insulin-like growth factor 1 is associated with gonadal activation by recombinant growth hormone in immature rats

BackgroundIn children, recombinant human growth hormone (rhGH) therapy for treatment of short stature has raised concerns of the early onset of puberty. Puberty is initiated by the activation of the hypothalamus-pituitary-gonad axis. Insulin-like growth factor-1 (IGF1) has been known to mediate physiologic effects of GH. To understand the mechanism of precocious sexual maturation following prepubertal GH therapy, the effects of rhGH on the hypothalamus-pituitary-gonad axis were examined in the immature male rats.MethodsImmature male rats were given by daily injection of rhGH (1 or 2 IU/kg) from postnatal day (PND) 21 to PND 23 or 30. The effects of rhGH on kisspeptin-GnRH-LH system in the hypothalamus-pituitary axis, systemic and testicular IGF1, spermatogenesis, steroidogenesis, and circulating testosterone levels were examined. The effects of rhGH on the IGF1 expression and steroidogenesis were examined in progenitor LCs in vitro.ResultsTesticular steroidogenic pathway and spermatogenesis marker mRNA levels, number and size of 17β-hydroxysteroid dehydrogenase (+) LCs, and blood testosterone levels of rhGH rats were significantly higher than those of controls on PNDs 24 and 31. Hypothalamic Kiss1 and Gnrh1 mRNA of rhGH rats were significantly higher than those of controls on PND 24, indicating early activation of hypothalamic kisspeptin-GnRH neurons by rhGH. Hypothalamic Igf1 mRNA levels of rhGH rats were significantly higher than those of controls on PND 24 but significantly lower than those of controls on PND 31. Testicular Igf1 mRNA levels were significantly higher in rhGH rats than in the controls on PNDs 24 and 31 whereas circulating IGF1 levels were not. In progenitor LCs, rhGH significantly increased Igf1 and steroidogenic pathway mRNA levels and testosterone production.ConclusionsLocal increases in testicular IGF1 might be an important mediator of gonadal maturation via activation of LCs steroidogenesis in immature rats given rhGH.

Association Between Recombinant Growth Hormone Therapy and All-Cause Mortality and Cancer Risk in Childhood: Systematic Review and Meta-Analysis.

ObjectivesThe safety of recombinant human growth hormone (rhGH) treatment in childhood and the role of rhGH therapy in promoting tumorigenesis and progression have been the subject of debate for decades. We aimed to systematically assess the relationship between rhGH therapy in children and adolescents and clinical outcomes, including all-cause mortality, cancer mortality, cancer incidence, and risk of the second neoplasm.MethodsLiterature retrieval, study selection, and data extraction were completed independently and in duplicate. Effect-size estimates are expressed as standardized mortality ratios (SMRs), standardized incidence ratio (SIR), and relative risk (RR) with a 95% CI.ResultsData from 24 articles, involving 254,776 persons, were meta-analyzed. Overall analyses revealed the association of rhGH therapy was not statistically significant with all-cause mortality (SMR = 1.28; 95% CI: 0.58–2.84; P = 0.547; I2 = 99.2%; Tau2 = 2.154) and cancer mortality (SMR = 2.59; 95% CI: 0.55–12.09; P = 0.228; I2 = 96.7%; Tau2 = 2.361) and also cancer incidence (SIR = 1.54; 95% CI: 0.68–3.47; P = 0.229; I2 = 97.5%; Tau2 = 2.287), yet statistical significance was observed for second neoplasm (RR = 1.77; 95% CI: 1.33–2.35; P = 0.001; I2 = 26.7%; Tau2 = 0.055). Differences in the geographic region, gender, treatment duration, mean rhGH dose, overall rhGH exposure dose, and initial disease accounted for heterogeneity in the subgroup analyses.ConclusionOur findings indicate that the rhGH therapy is not related to all-cause mortality and cancer mortality and cancer incidence, yet it seems to trigger a second tumor risk. Future prospective studies are needed to confirm our findings and answer the more challenging question regarding the optimal dose of rhGH therapy in children and adolescents.

Molecular chaperone GroEL-GroES enhances the soluble expression of biologically active ovine growth hormone in the prokaryotic system

Growth hormone (GH) plays important roles in growth and development of mammalian animals and is valuable for many applications. This study aimed to express and purify biological active recombinant ovine growth hormone (roGH) through prokaryotic expression system. The roGH coding sequence was ligated into the prokaryotic expression vector and transformed into Escherichia coli (E. coli) for protein expression. Factors that influence the roGH expression were examined and the appropriate culture temperature (20 °C) and inducer (IPTG) concentration (25 μM) were determined. To enhance the soluble expression of the protein, co-expression with the molecular chaperone GroEL-GroES was utilized and eventually achieved a high yield of soluble roGH expressed in E. coli. Further, the fusion tag in expressed target protein could be efficiently removed through thrombin-specific cleavage. The expressed roGH was identified by Western blotting and the LC-MS spectrum confirmed its molecular weight of 22749.22 Da. Finally, the purified roGH had an expected biological activity when assayed in cell models in vitro and experimental mouse in vivo. In conclusion, the present study established an efficient and simple approach to produce recombinant GH, and facilitate relevant research and applications.

Design and production of a novel chimeric human growth hormone superagonist fused to human Fc domain.

Background and purpose:Growth hormone (GH) has been known as a crucial metabolic hormone expressed at the pituitary and the other number of cells and tissues and responsible for body growth. Because of the short half-life of GH, daily subcutaneous injections were shown to be more effective for GH therapy. This represents a burden for patients. So, there is a strong effort from the industry to create a long-acting form of GH and lots of technologies like GH fusion proteins are used to increase GH half-life.Experimental approach:In this study, the Fc domain of human IgG1 with serine-glycine linkers was attached to the C-terminal of a GH superagonist via molecular cloning. The presence of recombinant vector in E. coli host was confirmed by PCR. SDS-PAGE and western blot analysis showed the expression of recombinant proteins in the bacterial lysate. The binding ability to growth hormone receptors is determined by ELISA.Findings / Results:Our results showed that the novel SupGH-Fc has a good binding affinity to its receptor in ELISA in comparison to standard GH, although it has a big size.Conclusion and implications:Our data in this study clearly demonstrated the expression of the SupGH-Fc in a recombinant protein expression system. It is an introduction to the production of the new recombinant GH, which can bind to its receptor more effectively than commercial growth hormones and also might have a longer half-life.

Growth Velocity and Economic Aspects of Human Growth Hormone Treatment in an Egyptian Cohort with Multiple Pituitary Hormone Deficiency: A Retrospective Minireview

Abstract 
 Background: Multiple pituitary hormone deficiency (MPHD) is a chronic lifelong disease. Human recombinant growth hormone (hGH) treatment is the optimal therapy for short stature in children with growth hormone (GH) deficiency in patients with MPHD and can effectively increase growth velocity (GV) to attain adult heights within the target range. Objective: to assess the GV during hGH treatment of children with MPHD, to analyze the characteristics of patients and to investigate the possible factors that might affect their height gain. Methods: Data from 18 (8 females) children and adolescents with MPHD with GH, thyroid stimulating hormone, gonadotropin and adrenocorticotropic hormone deficiencies were collected. Subjects were divided into groups: 12 pubescent patients and 6 pre-pubescent patients. Anthropometric measurements were reported regularly for one year. Results: age at onset of study was 13.44±4.66 years. CT and MRI findings were positive in 77.8 %. Peak GH levels after Clonidine and Insulin were 4.06±2.61 and 5.39±4.2 ng/ml respectively. GH was received in a dose of 0.95±0.5 mg/day. Height gain during the period of the study was 3.5±0.47cm /year. The predicted adult height at the first and last visits and delta predicted adult height between the first and last visits were 155.78±10.159, 156.71±7.22 and 0.93±4.64 cm respectively. The cost in dollars was identified using Markov cost-effectiveness simulation model as 98.87±52.4 dollars per one cm height gain, with a total of 346.07±183.42 US dollars/patient/year. For a hGH dose of 0.02±0.01 mg/kg/d (0.95±0.5mg/day). There was a positive correlation between height gain during the study period and both the height SDS at presentation and dose of GH mg/kg/d. Conclusion: the height gain and the cost were higher amongst females than males with MPHD. Height at presentation and hGH dose seemed to be an effective predictor for height gain in patients with MPHD.

Studies of IGF-I and Klotho Protein in Relation to Anabolic-Androgenic Steroid and Growth Hormone Administrations.

It has been suggested to longitudinally monitor Insulin-like growth factor I (IGF-I) as a biomarker for the detection of recombinant growth hormone (GH). Subsequently, it is of interest to understand any confounders of endogenous IGF-I. Herein we have studied if serum IGF-I concentration is affected by the intake of anabolic androgenic steroids (AAS) and the potential connection between IGF-I and klotho protein. Moreover, the usefulness of klotho as a biomarker for recombinant GH intake was assessed in healthy male volunteers. An ongoing administration of AAS did not affect the levels of IGF-I. Klotho protein was ~30% higher in men with an ongoing AAS use compared to those with previous (>2 months ago) AAS use, and the serum klotho protein correlated negatively with luteinizing hormone (LH) (rs = −0.38, p = 0.04) and follicle stimulating hormone (FSH) (rs = −0.35, p = 0.05) levels. Serum IGF-I and klotho concentrations showed no correlation in the AAS using population but showed a strong negative correlation in healthy volunteers (rs = −0.86, p = 0.006). The intake of recombinant GH did not affect the serum concentrations of the klotho levels. In conclusion, IGF-I was not affected by supra-physiological AAS doses in men. Interestingly, an association between AAS intake and serum klotho was seen. The usefulness of klotho as an androgen biomarker warrants further studies, whereas klotho can be discarded as a promising biomarker for GH doping.

Novel Loss-of-Function Mutations in NPR2 Cause Acromesomelic Dysplasia, Maroteaux Type.

Acromesomelic dysplasia, Maroteaux type (AMDM) is a rare skeletal dysplasia characterized by severe disproportionate short stature, short hands and feet, normal intelligence, and facial dysmorphism. Homozygous or compound heterozygous mutations in the natriuretic peptide receptor 2 (NPR2) gene produce growth-restricted phenotypes. The current study was designed to identify and characterize NPR2 loss-of-function mutations in patients with AMDM and to explore therapeutic responses to recombinant growth hormone (rhGH). NPR2 was sequenced in two Chinese patients with AMDM via next generation sequencing, and in silico structural analysis or transcript analysis of two novel variants was performed to examine putative protein changes. rhGH treatment was started for patient 1. Three NPR2 mutations were identified in two unrelated cases: two compound heterozygous mutations c.1112G>A p.(Arg371Gln) and c.2887+2T>C in patient 1 and a homozygous mutation c.329G>A p.(Arg110His) in patient 2, yielding distinct phenotypes. RNA extracted from peripheral blood cells of patient 1 showed alternatively spliced transcripts not present in control cells. Homology modeling analyses suggested that the c.1112G>A p.(Arg371Gln) mutation disrupted the binding of NPR-B homodimer to its ligand (C-type natriuretic peptide) in the extracellular domain as a result of global allosteric effects on homodimer formation. Thus, c.2887+2T>C and c.1112G>A p.(Arg371Gln) in NPR2 were loss-of-function mutations. Furthermore, rhGH therapy in patient 1 increased the patient’s height by 0.6SDS over 15 months without adversely affecting the trunk-leg proportion. The short-term growth-promoting effect was equivalent to that reported for idiopathic short stature. Overall, our findings broadened the genotypic spectrum of NPR2 mutations in individuals with AMDM and provided insights into the efficacy of rhGH in these patients.

Effect of systemic administration of recombinant growth hormone on rotator cuff repair a rat model study

Shoulder rotator cuff injuries are prevalent among the elderly. Rotator cuff tears, like osteoarthritis, are an inevitable aspect of aging. The only difference is that soft tissue rather than cartilage is involved in the degenerative process.We hypothesized that exogenous systemic administration of recombinant growth hormone would increase the concentration of various growth factors involved in rotator cuff healing,Forty-eight Sprague-Dawley rats (Charles River, male, 400-450 g) were subjected to unilateral detachment repair of the supraspinatus and infraspinatus tendons at Konkuk University per Institutional Animal Care Committee recommendations.The rats were divided in two groups one were injected with recombinant GH and controls. Initially an artificial rotator cuff tear was created and later repaired with vicryl 4-0. The animals were sacrificed at 1, 3, 6, and 12 weeks. The rotator cuff was removed enmasse. Both groups were compared histologically and immunologically for collagen 1 and 3. Statistical analysis between both the groups was done using SPSS software.The recombinant GH helped in early healing of rotator cuff tears if injected systemically. More clinical trials need to be done before the exact dose can be determined for humans.

Effect of feedings with different protein levels and dietary supplemental rElGH on culture performances of sex reversed Oreochromis niloticus (Linnaeus, 1758)

This study aims to evaluate the culture performance of tilapia (Oreochromis niloticus) that have been treated with 17α-methyltestosterone (MT) and without MT (w-MT), feed with different protein levels (20, 24, and 28%) and recombinant Epinephelus lanceolatus growth hormone (rElGH)-diet. The research was conducted in 9 treatments and triplicate. Tilapia larvae were soaked twice, totaling 500 larvae, at the age of 10 days after hatching (DAH) and the age of 14 DAH was soaked for 4 hours using 1/l MT 2 mg/l solution. Fish maintenance was conducted in an aquarium of 1.0x0.5x0.5 m3 in the first month, and three months later in net cages (2.0x2.0x1.5 m3). Daily growth rate (DGR) and biomass gain (BG) were increased in line with increasing feed protein content and rElGH supplementation. The highest DGR and BG values were MT+28+rElGH (P 0.05) treatment. The highest feed consumption and the lowest feed conversion ratio were also obtained in the MT+28+rElGH treatment (P 0.05). Fish survival was ranged from 79.89 to 90.28% (P 0.05). The highest profit potential was found in the MT+28+rElGH treatment. The efficient aquaculture can be obtained by feeding sex-reversed tilapia at a protein level of 28% and a diet supplemented with rElGH.Keywords:Feed conversion ratioGrowth hormoneProtein retention17α-methyltestosterone

Growth hormone isoform testing in capillary dried blood spots: Results from single and multiple dose administration studies and large-scale field collections.

A multiphase study was designed to examine the detectability of human growth hormone (GH) use in capillary dried blood spots (DBS). First, 13 subjects self-injected a single, 2-mg dose of somatropin and collected capillary DBS samples for 24 h. Next, nine subjects self-injected 2-mg somatropin, six times over the course of 11 days; DBS were collected intermittently following dosing. Finally, a nondrug, large-scale field study involved DBS collections from an athlete and staff population over 3 years. All DBS samples were self-collected using the Tasso M20 device and were analyzed for the presence of GH using the WADA-approved GH isoforms test. Following the single dose, positive detection within 12 h of dosing was 86% and 56% sensitive on Kits 1 and 2, respectively. In the multidose study, detection within 12 h was 85% and 69% sensitive on Kits 1 and 2, respectively. No positives were detected outside the 12-h window following a single dose, wherein detection was 5.6% sensitive at 24-h in the multidose study. Combining the 12-h windows from both studies, 100% of samples had measurable recombinant (REC) and pituitary (PIT) GH concentrations above the assay LoD, 0.041 ng/ml. Finally, 1213 samples were collected in the large-scale field study: 189 showed REC and PIT concentrations above the LoD; none returned positive results. GH is detectable in capillary DBS using the isoforms method for 12-24 h following use. While detection is short lived, transitioning to a DBS self-collection method can allow more frequent testing and increase deterrence to GH abuse.

Mecasermin (Increlex)


 CADTH recommends that Increlex should be reimbursed by public drug plans for the treatment of treatment of growth failure in children and adolescents from 2 to 18 years with confirmed severe primary insulin-like growth factor-1 deficiency (SPIGFD) if certain conditions are met.
 Increlex should only be covered to treat patients who are at least 2 years of age with confirmed diagnosis of SPIGFD and in whom epiphyseal growth plates have not yet closed.
 Increlex should only be reimbursed if prescribed by a pediatric endocrinologist, if it is not prescribed in combination with recombinant growth hormone treatment, and the price of Increlex is reduced.

Slipped Capital Femoral Epiphysis Associated with Endocrinopathy: A Narrative Review.

Slipped capital femoral epiphysis (SCFE) has a well-documented association with underlying endocrine conditions, including thyroid hormone aberrations and parathyroid dysfunction. Recombinant growth hormone therapy has also been identified as a risk factor for the development of SCFE. Presentation before their 10th birthday or after their 16th birthday along with height of <10th percentile are reliable risk factors for identifying children with an SCFE who are at a heightened risk for an underlying endocrinopathy and can been used to guide selective laboratory testing. Patients with unilateral SCFE presentations with an underlying endocrinopathy are at a heightened risk for contralateral slip development and should be treated with prophylactic fixation.

The Promise and Challenges of Determining Recombinant Bovine Growth Hormone in Milk.

Recombinant bovine growth hormone (rbGH) is produced in large quantities and widely used in a number of countries worldwide to stimulate milk production in dairy animals. The use of this compound in animal production is strictly regulated by food safety directives in force, in particular in the European Union (EU). Although analytical strategies for the detection of rbGH in blood have been successfully reported over the past 15 years, they do not fully answer the expectations of either competent authorities or industrials that would expect measuring its occurrence directly in the milk. As a matrix of excretion but also of consumption, milk appears indeed as the matrix of choice for detecting the use of rbGH in dairy animals. It also allows large volumes to be collected without presenting an invasive character for the animal. However, rbGH detection in milk presents several challenges, mainly related to the sensitivity required for its detection in a complex biological matrix. This review article presents the specific difficulties associated with milk and provides an overview of the analytical strategies reported in the literature and whether they concern indirect or direct approaches to the detection of rbGH administration to animals, with applications either for screening or confirmation purposes.