Diurnal and Daily Variations in Growth Hormone and Growth Hormone Stimulation Test in Male Cynomolgus Monkeys.
This study characterized growth hormone (GH) secretion patterns and responsiveness to exogenous GH-releasing hormone (GHRH) in adult male cynomolgus monkeys, with the goal of evaluating their suitability as a model for pituitary toxicity research. Two groups of ten animals were used to assess diurnal and day-to-day GH variation via serial serum sampling, while a separate four-animal-per-group crossover examined GH responses to intravenous pralmorelin hydrochloride (a GHRH analog) versus saline. GH was measured by ELISA. The study found a diurnal pattern resembling that of humans, with GH rising in the late morning, dipping around midday, and peaking at night. Considerable inter- and intra-individual daily variation was also observed over five consecutive days. In the stimulation test, GHRH-treated animals showed significantly higher GH concentrations at 0.5 and 1 hour post-administration compared to controls. The authors conclude that cynomolgus monkeys share key GH secretion characteristics with humans and may serve as a relevant non-clinical model. Limitations include small sample sizes, male-only subjects, and the non-human primate setting, meaning direct translation to human physiology or clinical applications requires caution.
Why this grade: The study was conducted entirely in cynomolgus monkeys (n=4–10 per group) with no human subjects, limiting direct clinical inference despite the physiological parallels drawn to humans.
Background/aim Growth hormone (GH) secretion patterns differ across species. Humans exhibit a nocturnal surge, while rodents exhibit ultradian pulses. In cynomolgus monkeys, diurnal and daily variations and responsiveness to exogenous GH-releasing hormone (GHRH) remain insufficiently defined in non-clinical studies. This study aimed to characterize GH secretion patterns and evaluate responsiveness to exogenous GHRH in adult male cynomolgus monkeys for pituitary toxicity studies. Materials and methods Serum from 10 animals was collected between 10:00 and 22:30 and again at 10:30 on the following day to evaluate diurnal variation. Serum from 10 additional animals was collected once daily between 9:00 and 10:00 across five days to evaluate daily variation. In the GH stimulation test, four animals received intravenous pralmorelin hydrochloride (as GHRH) and four received physiological saline between 11:00 and 11:30. Serum was collected before and at 0.5, 1, and 2 h after administration. GH concentration was measured with enzyme-linked immunosorbent assay. Results Diurnal variation was observed, with concentrations increasing from 10:00 to 11:30, transiently dropping to their lowest at 12:30 and peaking at 22:30, similar to the pattern in humans. Daily variation was also observed inter- and intra-individually across five days. In the stimulation test, compared to the control group, the GHRH group showed higher GH concentrations at 0.5 h ( p p Conclusion In adult male cynomolgus monkeys, diurnal and daily GH variations and responsiveness to exogenous GHRH were confirmed. Morning GHRH administration in the stimulation test, when basal GH is low and diurnal influence is minimal, and multi-timepoint sampling are recommended for reliable GH assessment. These findings suggest that cynomolgus monkeys are a suitable model for pituitary toxicity studies.
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