Endogenous Growth Hormone Secretion Research Articles

Somapacitan (Sogroya)


 CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
 The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.
 This review assesses somapacitan (Sogroya), 5 mg/1.5 mL (3.3 mg/mL), 10 mg/1.5 mL (6.7 mg/mL), 15 mg/1.5 mL (10 mg/mL) as a prefilled pen for subcutaneous injection.
 Indication: For the long-term treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone (growth hormone deficiency).

Somapacitan (Sogroya)


 CADTH recommends that Sogroya should be reimbursed by public drug plans for the long-term treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone (growth hormone deficiency [GHD]) if certain conditions are met.
 Sogroya should only be covered to treat children who are at least 2.5 years of age, have not reached puberty yet, and are diagnosed with GHD.
 Sogroya should only be reimbursed for a patient who is under the care of a pediatric endocrinologist and whose growth plates have not closed if Sogroya does not cost more than somatropin and somatrogon.

Diagnosis and testing for growth hormone deficiency across the ages: a global view of the accuracy, caveats, and cut-offs for diagnosis.

Growth hormone deficiency (GHD) is a clinical syndrome that can manifest either as isolated or associated with additional pituitary hormone deficiencies. Although diminished height velocity and short stature are useful and important clinical markers to consider testing for GHD in children, the signs and symptoms of GHD are not always so apparent in adults. Quality of life and metabolic health are often impacted in patients with GHD; thus, making an accurate diagnosis is important so that appropriate growth hormone (GH) replacement therapy can be offered to these patients. Screening and testing for GHD require sound clinical judgment that follows after obtaining a complete medical history of patients with a hypothalamic-pituitary disorder and a thorough physical examination with specific features for each period of life, while targeted biochemical testing and imaging are required to confirm the diagnosis. Random measurements of serum GH levels are not recommended to screen for GHD (except in neonates) as endogenous GH secretion is episodic and pulsatile throughout the lifespan. One or more GH stimulation tests may be required, but existing methods of testing might be inaccurate, difficult to perform, and can be imprecise. Furthermore, there are multiple caveats when interpreting test results including individual patient factors, differences in peak GH cut-offs (by age and test), testing time points, and heterogeneity of GH and insulin-like growth factor 1 assays. In this article, we provide a global overview of the accuracy and cut-offs for diagnosis of GHD in children and adults and discuss the caveats in conducting and interpreting these tests.

Detection of the growth hormone secretagogue MK-0677 in equine hair following oral administration.

MK-0677 (ibutamoren) is an orally active non-peptide growth hormone secretagogue that binds to the ghrelin receptor stimulating the secretion of endogenous growth hormone. It is one of the most prevalent performance-enhancing compounds currently available online and is potentially subject to abuse both in human and equine sports. The aim of the current study was to investigate whether it could be detected in equine hair following oral administration of MK-0677 mesylate to a Thoroughbred racehorse. MK-0677 and its O-dealkylated metabolite were extracted using an existing method for prohibited substances in equine hair and analysed by liquid chromatography tandem mass spectrometry. This enabled the detection of MK-0677 in all hair samples collected, up to 209 days in mane and 358 days in tail. A follow-up methodology with an extensive wash procedure was carried out for selected hair samples, which unambiguously verified the presence of MK-0677. Wash criteria to differentiate between internal incorporation (via bloodstream) and external deposition (via sweat and sebum) was also assessed and indicated internal incorporation for the samples collected at later time points (≥52 days) and a combination of internal incorporation and external deposition for hair samples collected at the earlier time point (2days).

Effect of long-acting growth hormone treatment on endogenous growth hormone secretion in prepubertal patients with idiopathic short stature: A preliminary study

Long-acting growth hormone (LAGH) is emerging to be a new preparation for treatment of short stature. We aimed to determine whether 12-month treatment with LAGH in patients with idiopathic short stature has an effect on the nocturnal endogenous growth hormone (GH) secretion and metabolic consequences and efficacy. Participants included 10 GH-naïve prepubertal children with idiopathic short stature (ISS). One patient was withdrawn due to own decline during study. Participants were randomized on a 1:1 ratio to receive either a daily GH (0.37 mg/kg/week) or once-weekly LAGH (0.7 mg/kg/week) over a 12-month period. Nocturnal endogenous GH secretory profiles obtained from 12-h blood samplings at 30-min interval were assessed at baseline and 2 weeks after the completion of GH treatment. Post-treatment changes in height velocity, height standard deviation score (SDS), metabolic parameters, and adverse events were measured. A total of 4 patients received LAGH, and 5 patients received daily GH. Nocturnal endogenous GH secretory profiles, such as mean serum GH concentrations, frequency, amplitude, interpulse interval of spontaneous GH secretory bursts, and mass of GH released per secretory burst were similar at baseline and after 12-month treatment in both groups. The efficacy and safety after LAGH treatment for 12 months were similar to those of daily GH. In conclusions, these findings indicated that LAGH does not suppress endogenous GH secretion, and can be used for treatment of non-GH deficient short stature with similar efficacy and safety compared to daily GH. These may contribute to define and develop treatment and follow-up protocols for LAGH use in ISS patients.

Somatrogon (Ngenla)


 CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
 The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.
 This review assesses somatrogon (Ngenla), 24 mg/1.2 mL (20 mg/mL) as a pre-filled pen or 60 mg/1.2 mL (50 mg/mL) as a pre-filled pen for SC injection.
 Indication: The long-term treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone (growth hormone deficiency).

Somatrogon: First Approval.

Somatrogon (NGENLA®), a long-acting human growth hormone based on C-terminal peptide technology, is in development by Pfizer and OPKO Health for the treatment of growth hormone deficiency in pediatric and adult patients. Administered as a once-weekly subcutaneous injection, somatrogon reduces treatment burden relative to once-daily human growth hormone therapy while providing non-inferior efficacy. Somatrogon received its first approval in October 2021 in Canada for the long-term treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone (growth hormone deficiency). This article summarizes the milestones in the development of somatrogon leading to this first approval for the treatment of growth hormone deficiency.

Lonapegsomatropin: Pediatric First Approval.

Lonapegsomatropin (lonapegsomatropin-tcgd; SKYTROFA®), a long-acting prodrug of somatropin (human growth hormone), is in development by Ascendis Pharma as a treatment for growth hormone deficiency in pediatric and adult patients. Lonapegsomatropin received its first approval in August 2021 in the USA for the treatment of pediatric patients at least 1 year of age (and weighing ≥ 11.5 kg) with growth failure due to inadequate secretion of endogenous growth hormone. Lonapegsomatropin is administered as a once-weekly subcutaneous injection; the sustained release of somatropin from lonapegsomatropin eliminates the need for daily somatropin injections. This article summarizes the milestones in the development of lonapegsomatropin leading to this first pediatric approval for the treatment of growth hormone deficiency.

The history, physiology and treatment safety of growth hormone.

Growth hormone treatment was introduced in the 1950s to address growth disturbances and metabolic abnormalities. Hundreds of thousands of children have been treated, with gradual expansion of treatment indications. From initially being offered only to patients with severe growth hormone deficiency, today many children are treated for conditions in which the associated short stature is not primarily thought to be due to deficient endogenous growth hormone secretion. This review discusses the history, physiology and safety of growth hormone treatment, with focus on the long-term risks of mortality, cardiovascular morbidity and cancer. Conclusion: Continuous follow-up is needed to increase our knowledge of the long-term treatment safety.

Stimulation of endogenous pulsatile growth hormone secretion by activation of growth hormone secretagogue receptor reduces the fat accumulation and improves the insulin sensitivity in obese mice.

Obese individuals often show low growth hormone (GH) secretion, which leads to reduced lipid mobilization and further fat accumulation. Pharmacological approaches to increase GH levels in obese individuals by GH injection or GH-releasing hormone receptor agonist showed promising effects on fat reduction. However, side effects on glucose metabolism and the heavy costs on making large peptides hindered their clinical application. Here, we tested whether stimulation of endogenous GH secretion by a synthetic GH secretagogue receptor (GHSR) agonist, hexarelin, improved the metabolism in a hyperphagic obese mouse model. Male melanocortin 4 receptor knockout mice (MC4RKO) were pair-fed and received continuous hexarelin (10.56μg/day) or vehicle infusion by an osmotic pump for 3-4weeks. Hexarelin treatment significantly increased the pulsatile GH secretion without detectable alteration on basal GH secretion in MC4RKO mice. The treated mice showed increased lipolysis and lipid oxidation in the adipose tissue, and reduced de novo lipogenesis in the liver, leading to reduced visceral fat mass, reduced triglyceride content in liver, and unchanged circulating free fatty acid levels. Importantly, hexarelin treatment improved the whole-body insulin sensitivity but did not alter glucose tolerance, insulin levels, or insulin-like growth factor 1 (IGF-1) levels. The metabolic effects of hexarelin were likely through the direct action of GH, as indicated by the increased expression level of genes involved in GH signaling pathways in visceral adipose tissues and liver. In conclusion, hexarelin treatment stimulated the pulsatile GH secretion and reduced the fat accumulation in visceral depots and liver in obese MC4RKO mice with improved insulin sensitivity without altered levels of insulin or IGF-1. It provides evidence for managing obesity by enhancing pulsatile GH secretion through activation of GHSR in the pituitary gland.

Quantification of the endogenous growth hormone and prolactin lowering effects of a somatostatin-dopamine chimera using population PK/PD modeling

A phase 1 clinical trial in healthy male volunteers was conducted with a somatostatin-dopamine chimera (BIM23B065), from which information could be obtained on the concentration-effect relationship of the inhibition of pulsatile endogenous growth hormone and prolactin secretion. Endogenous growth hormone profiles were analyzed using a two-step deconvolution-analysis-informed population pharmacodynamic modeling approach, which was developed for the analyses of pulsatile profiles. Prolactin concentrations were modelled using a population pool model with a circadian component on the prolactin release. During treatment with BIM23B065, growth hormone secretion was significantly reduced (maximal effect [EMAX] = − 64.8%) with significant reductions in the pulse frequency in two out of three multiple ascending dose cohorts. A circadian component in prolactin secretion was identified, modelled using a combination of two cosine functions with 24 h and 12 h periods. Dosing of BIM23B065 strongly inhibited (EMAX = − 91%) the prolactin release and demonstrated further reduction of prolactin secretion after multiple days of dosing. This study quantified the concentration-effect relationship of BIM23B065 on the release of two pituitary hormones, providing proof of pharmacology of the chimeric actions of BIM23B065.

Mode of GH administration and gene expression in the female rat brain.

The endogenous secretion of growth hormone (GH) is sexually dimorphic in rats with females having a more even and males a more pulsatile secretion and low trough levels. The mode of GH administration, mimicking the sexually dimorphic secretion, has different systemic effects. In the brains of male rats, we have previously found that the mode of GH administration differently affects neuron-haemoglobin beta (Hbb) expression whereas effects on other transcripts were moderate. The different modes of GH administration could have different effects on brain transcripts in female rats. Hypophysectomised female rats were given GH either as injections twice daily or as continuous infusion and GH-responsive transcripts were assessed by quantitative reverse transcription polymerase chain reaction in the hippocampus and parietal cortex (cortex). The different modes of GH-administration markedly increased Hbb and 5'-aminolevulinate synthase 2 (Alas2) in both brain regions. As other effects were relatively moderate, a mixed model analysis (MMA) was used to investigate general effects of the treatments. In the hippocampus, MMA showed that GH-infusion suppressed glia- and neuron-related transcript expression levels, whereas GH-injections increased expression levels. In the cortex, GH-infusion instead increased neuron-related transcripts, whereas GH-injections had no significant effect. Interestingly, this contrasts to previous results obtained from male rat cortex where GH-infusion generally decreased expression levels. In conclusion, the results indicate that there is a small but significant difference in response to mode of GH administration in the hippocampus as compared to the cortex. For both modes of GH administration, there was a robust effect on Hbb and Alas2.

Determination of growth hormone releasing peptides metabolites in human urine after nasal administration of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin.

Growth hormone releasing peptides (GHRPs) stimulate secretion of endogenous growth hormone and are listed on the World Anti-Doping Agency (WADA) Prohibited List. To develop an effective method for GHRPs anti-doping control we have investigated metabolites of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin in urine after nasal administration. Each compound was administrated to one volunteer. Samples were collected for 2 days after administration, processed by solid-phase extraction on weak cation exchange cartridges and analyzed by means of nano-liquid chromatography - high resolution mass spectrometry. Six metabolites of GHRP-1 were identified. GHRP-1 in the parent form was not detected. GHRP-1 (2-4) free acid was detected in urine up to 27 h. GHRP-2, GHRP-2 free acid and GHRP-2 (1-3) free acid were detected in urine up to 47 h after administration. GHRP-6 was mostly excreted unchanged and detected in urine 23 h after administration, its metabolites were detectable for 12 h only. Hexarelin and Ipamorelin metabolized intensively and were excreted as a set of parent compounds with metabolites. Hexarelin (1-3) free acid and Ipamorelin (1-4) free acid were detected in urine samples after complete withdrawal of parent substances. GHRPs and their most prominent metabolites were included into routine ultra-pressure liquid chromatography-tandem mass spectrometry procedure. The method was fully validated, calibration curves of targeted analytes were obtained and excretion curves of GHRPs and their metabolites were plotted. Our results confirm that the detection window after GHRPs administration depends on individual metabolism, drug preparation form and the way of administration.

Relationship between Growth Hormone and Cytokines in Short Children Undergoing Growth Hormone Stimulation Testing

Background: The relationship between growth hormone (GH) and cytokines remains unclear. Several studies have suggested that GH increases tumor necrosis factor (TNF)-α production in both children and adults. However, a number of studies have demonstrated a negative correlation between GH and TNF α. The aim of this study is to explore the relationship between endogenous GH secretion and certain pro and anti-inflammatory cytokines in short children undergoing GH stimulation testing for evaluation for GH deficiency. Methods: Plasma growth hormone, TNF α, CRP, IL-6, IL1-β, IL-4 and IL-10 levels are obtained at baseline and every 30 minutes for 150 minutes following two provocative agents (clonidine, and either arginine or glucagon). Results: Among the 23 children, 7 are found to be GH deficient. No significant differences in baseline TNF α levels are found between GH deficient and GH sufficient children. No correlation is identified between TNF α levels and GH levels during stimulation testing. Furthermore, no relationship is found between GH and pro-inflammatory cytokines or GH and anti-inflammatory cytokines. Conclusion: Our results do not demonstrate an acute relationship between endogenous GH secretion and the cytokines examined.

Effect of Growth Hormone on Dawn Phenomenon in Healthy Adults

The purpose of this study was to investigate the involvement of growth hormone in the diurnal variation of insulin sensitivity in healthy adults. Afternoon (16:00 hr) or night (23:00 hr) pretreatment with a subcutaneous injection of normal saline, human growth hormone to mimic the normal nocturnal rise in growth hormone, or octreotide to inhibit endogenous growth hormone secretion to create a state of relative nocturnal growth hormone deficiency, was given 16 hours before undergoing the modified insulin suppression test in healthy subjects. The morning and evening experiments were separated by an interval of at least 3 days. Thus, each subject was tested on six separate occasions arranged in a random order. A higher value of the steady-state plasma glucose (SSPG) is indicative of lower insulin sensitivity. Plasma glucose, serum insulin, insulin-like growth factor-1, nonesterified fatty acids (NEFA), and metabolic clearance rate of insulin (MCRI) were measured. In the normal saline and human growth hormone groups, SSPG levels were lower in the morning than in the evening. Evening SSPG levels, MCRI, and NEFA concentrations were higher in the participants treated with normal saline and growth hormone than in the octreotide group. Differences in SSPG levels between the morning and evening values were higher in the participants pretreated with normal saline and growth hormone than in those treated with octreotide. A diurnal variation in insulin sensitivity existed in healthy subjects. These results provided direct evidence that the role of growth hormone in regulating insulin sensitivity might be related to changes in the MCRI and the metabolism of NEFA in healthy subjects.

Growth Hormone Dose-Dependent Pubertal Growth: A Randomized Trial in Short Children with Low Growth Hormone Secretion

Background/Aims: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i.e. idiopathic isolated GH deficiency. Methods: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH 33 µg/kg/day for ≥1 year. They were randomized to receive 67 µg/kg/day (GH⁶⁷) given as one (GH^67×1; n = 35) or two daily injections (GH^33×2; n = 36), or to remain on a single 33 µg/kg/day dose (GH^33×1; n = 40). Growth was assessed as height_SDSgain for prepubertal, pubertal and total periods, as well as AH_SDS versus the population and the midparental height. Results: Pubertal height_SDSgain was greater for patients receiving a high dose (GH⁶⁷, 0.73) than a low dose (GH^33×1, 0.41, p < 0.05). AH_SDS was greater on GH⁶⁷ (GH^67×1, -0.84; GH^33×2, -0.83) than GH³³ (-1.25, p < 0.05), and height_SDSgain was greater on GH⁶⁷ than GH³³ (2.04 and 1.56, respectively; p < 0.01). All groups reached their target height_SDS. Conclusion: Pubertal height_SDSgain and AH_SDS were dose dependent, with greater growth being observed for the GH⁶⁷ than the GH³³ randomization group; however, there were no differences between the once- and twice-daily GH⁶⁷ regimens.

The Acute Effects of L-arginine on Hormonal and Metabolic Responses During Submaximal Exercise in Trained Cyclists

L-arginine may enhance endurance performance mediated by two primary mechanisms including enhanced secretion of endogenous growth hormone (GH) and as a precursor of nitric oxide (NO); however, research in trained participants has been equivocal. The purpose was to investigate the effect of acute L-arginine ingestion on the hormonal and metabolic response during submaximal exercise in trained cyclists. Fifteen aerobically trained men (age: 28 ± 5 y; body mass: 77.4 ± 9.5 kg; height: 180.9 ± 7.9 cm; VO2max: 59.6 ± 5.9 ml·kg- 1·min-1) participated in a randomized, double-blind, crossover study. Subjects consumed L-arginine (ARG; 0. 075 g·kg-1 body mass) or a placebo (PLA) before performing an acute bout of submaximal exercise (60 min at 80% of power output achieved at ventilatory threshold). The ARG condition significantly increased plasma L-arginine concentrations (~146%), while no change was detected in the PLA condition. There were no differences between conditions for GH, nonesterified fatty acids (NEFA), lactate, glucose, VO2, VCO2, RER, CHO oxidation, and NOx. There was reduced fat oxidation at the start of exercise (ARG: 0.36 ± 0.25 vs. PLA: 0.42 ± 0.23 g·min-1, p < .05) and an elevated plasma glycerol concentrations at the 45-min time point (ARG: 340.3 vs. PLA: 288.5 μmol·L-1, p < .05) after L-arginine consumption. In conclusion, the acute ingestion of L-arginine did not alter any hormonal, metabolic, or cardio-respiratory responses during submaximal exercise except for a small but significant increase in glycerol at the 45-min time point and a reduction in fat oxidation at the start of exercise.

Determination of insulin-like growth factor-I reference values using an immunoradiometric assay in a Brazilian adult population

Serum levels of total insulin-like growth factor I (IGF-I) reflect endogenous growth hormone (GH) secretion in healthy adults, which makes it a good diagnostic marker for screening of GH-related disorders. Studies also have supported a possible relation between IGF-I levels and the risk and prognostic for some malignancies, besides a relation between IGF-I levels and mortality. As the determination of the IGF-I normal values for local populations is strongly desired, the aim of this investigation was to determine reference values for IGF-I using an immunoradiometric assay (IRMA) in an adult Brazilian population of Rio de Janeiro city, since there is no other study using this methodology in Brazilian population, and that this method is widely used in Brazil and worldwide. The study included samples of blood taken from 484 healthy subjects (251 men and 233 women) aged 18-70. The subjects agreed with this study, approved by the Ethical Committee of the Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, Brazil. The samples were analyzed using a Diagnostic System Laboratories kit. For data analysis, age- and sex-specific figures were fitted after transformation of IGF-I values. In adulthood, a slow age-dependent decrease was found. There was no significant difference in IGF-I values between men and women. This study established age-specific IGF-I reference values, for a healthy Brazilian adult population, determined by a widely IGF-I, IRMA used currently in Brazil.

Growth hormone is positively associated with surrogate markers of bone turnover during puberty

Puberty is characterized by increases in growth hormone (GH) and insulin-like growth factor-1 (IGF-1) and the pubertal growth spurt. Bone formation and resorption also increase, consistent with increased bone metabolism. To determine the relationship between pubertal bone metabolism, GH and IGF-1. We hypothesized that bone turnover peaks at the time of greatest pubertal GH secretion. Subjects included 86 girls and boys, 9-17 years-old (BMI 10th-90th percentiles). Because higher endogenous GH secretion is associated with a higher nadir following oral glucose, we used the GH nadir following a 2-h OGTT as indicative of GH status. Fasting serum IGF-1, aminoterminal propeptide of type 1 procollagen (P1NP) and carboxy-terminal collagen crosslinks (CTX) were obtained. Subjects were grouped per expected timing of peak growth. Group 1: Tanner 1 girls and Tanner 1-2 boys (period preceding peak growth), Group 2: Tanner 2-3 girls and Tanner 3-4 boys (period of peak growth) and Group 3: Tanner 4-5 girls and Tanner 5 boys (period following peak growth). GH peaked at mid-puberty (Group 2) and IGF-1 in late puberty (Group 3). P1NP and CTX were highest in mid-puberty compared with early and late puberty (P = 0·0009 and 0·006 in girls and P = 0·005 and 0·04 in boys). GH, but not IGF-1, correlated with P1NP (r = 0·46 in both genders, P ≤ 0·008) and CTX (r = 0·37 and 0·38, P = 0·04 and 0·02 in girls and boys, respectively). Similarly, on regression modelling, GH (but not IGF-1) predicted both bone turnover markers in both genders. GH is strongly associated with pubertal bone metabolism, independent of systemic IGF-1 in girls and boys.

Assessment of endogenous growth hormone pulsatility in gelded yearling horses using deconvolution analysis

Hypothesis/objectives: Defining normal Growth Hormone (GH) secretory dynamics in the horse is necessary to understand altered GH dynamics related to issues like welfare and disease. Animals and methods: Twelve healthy yearlings and two mature Standardbreds were used to quantify GH secretion. Endogenous GH half-life was determined after administration of 1.0 µg/kg BW GH releasing hormone (GHRH). Exogenous GH half-life was determined after administration of 20 µg/kg BW recombinant equine GH (reGH) with and without suppression of endogenous GH secretion by somatostatin infusion (50 µg/m2/h). Pulse detection algorithm (Cluster) as well as deconvolution analysis was used to quantify GH secretory dynamics based on GH concentration-time series sampled every 5 min from 22:00 till 06:00 h. In addition, reproducibility, impact of sampling frequency and influence of altering initial GH half-life on parameter estimates were studied. Results: Mean endogenous GH half-life of 17.7 ± 4.4 (SD) min and mean exogenous half-life of 26.0 ± 2.9 min were found. The mean number of GH secretion peaks in 8 h was 12 ± 3.2. Ninety-nine percent of the total amount of GH secreted occurred in pulses, basal secretion was 0.012 ± 0.014 µg/L/min and half-life was 8.9 ± 2.6 min. Compared with a 5-min sampling frequency, 20- and 30-min sampling underestimated the number of secretory events by 45% and 100%, respectively. Conclusions: The deconvolution model used was valid to GH time series in Standardbreds. As in man, the equine pituitary gland secretes GH in volleys consisting of multiple secretory bursts, without measurable intervening tonic secretion. The required GH sampling frequency for the horse should be around 3 min. Clinical relevance: Defining normal GH secretory dynamics in the horse will make it possible to detect alterations in the GH axis due to pathophysiologic mechanisms as well as abuse of reGH.