To whoever knows... Who was the person that said this is the test to take an how did figure this out?
Was it someone at PM?
here is part of my research I found on the subject
Chapman IM, Hartman ML, Pieper KS, et al. Recovery of Growth Hormone Release from Suppression by Exogenous Insulin-Like Growth Factor I (IGF-I): Evidence for a Suppressive Action of Free Rather Than Bound IGF-I. Journal of Clinical Endocrinology & Metabolism 1998;83(8):2836-42. Recovery of Growth Hormone Release from Suppression by Exogenous Insulin-Like Growth Factor I (IGF-I): Evidence for a Suppressive Action of Free Rather Than Bound IGF-I
To determine the time course of recovery of GH release from insulin-like growth factor I (IGF-I) suppression, 11 healthy adults (18–29 yr) received, in randomized order, 4-h iv infusions of recombinant human IGF-I (rhIGF-I; 3 μg/kg•h) or saline (control) from 25.5–29.5 h of a 47.5-h fast. Serum GH was maximally suppressed within 2 h and remained suppressed for 2 h after the rhIGF-I infusion; during this 4-h period, GH concentrations were approximately 25% of control day levels [median (interquartile range), 1.2 (0.4–4.0) vs. 4.8 (2.8–7.9) μg/L; P < 0.05]. A rebound increase in GH concentrations occurred 5–7 h after the end of rhIGF-I infusion [7.6 (4.6–11.7) vs. 4.3 (2.5–6.0) μg/L; P < 0.05]. Thereafter, serum GH concentrations were similar on both days. Total IGF-I concentrations peaked at the end of the rhIGF-I infusion (432 ± 43 vs. 263 ± 44 μg/L; P < 0.0001) and remained elevated 18 h after the rhIGF-I infusion (360 ± 36 vs. 202 ± 23 μg/L; P = 0.001). Free IGF-I concentrations were approximately 140% above control day values at the end of the infusion (2.1 ± 0.4 vs. 0.88 ± 0.3 μg/L; P = 0.001), but declined to baseline within 2 h after the infusion. The close temporal association between the resolution of GH suppression and the fall of free IGF-I concentrations, and the lack of any association with total IGF-I concentrations suggest that unbound (free), not protein-bound, IGF-I is the major IGF-I component responsible for this suppression. The rebound increase in GH concentrations after the end of rhIGF-I infusion is consistent with cessation of an inhibitory effect of free IGF-I on GH release.
Yuen K, Frystyk J, Umpleby M, Fryklund L, Dunger D. Changes in Free Rather Than Total Insulin-Like Growth Factor-I Enhance Insulin Sensitivity and Suppress Endogenous Peak Growth Hormone (GH) Release following Short-Term Low-Dose GH Administration in Young Healthy Adults. Journal of Clinical Endocrinology & Metabolism 2004;89(8):3956-64. Changes in Free Rather Than Total Insulin-Like Growth Factor-I Enhance Insulin Sensitivity and Suppress Endogenous Peak Growth Hormone (GH) Release following Short-Term Low-Dose GH Administration in Young Healthy Adults
High-dose GH administration is commonly associated with impaired insulin sensitivity (SI) in humans. Paradoxically we have shown that low-dose GH (1.7 μg/kg•d) administration enhances β-cell function in young healthy adults. In the present double-blind, placebo-controlled, cross-over study, we explored the physiological effects of this low GH dose on glucose metabolism in 12 young healthy adults (seven males, 19–29 yr). At pretreatment and after each 14-d treatment block, overnight metabolic profiles were assessed followed by a hyperinsulinemic euglycemic clamp, whereas fasting blood samples were collected weekly.
In subjects treated with GH first (group A, n = 6), GH treatment increased total IGF-I (P < 0.05) and IGF binding protein-3 (P < 0.01) after 7 d, but these levels subsequently returned to pretreatment levels after 14 d. In contrast, free IGF-I increased (P < 0.05), and overnight GH pulse peak amplitude decreased (P < 0.01) after 14 d. In subjects treated with placebo first (group B, n = 6), all biochemical parameters were unchanged after placebo treatment, whereas the changes in free and total IGF-I were similar to those of group A after GH treatment. Combined clamp data from both groups A and B (n = 12) showed that 14-d GH treatment decreased overnight plasma insulin levels (P < 0.02) and hepatic glucose appearance (P < 0.05) and increased SI (P < 0.01). Of note, the GH-induced changes in SI positively correlated with the changes in free IGF-I (r = 0.72, P < 0.01).
In conclusion, low-dose GH administration enhanced SI and suppressed endogenous peak GH release, and we hypothesize that these effects are the direct result of increased serum levels of free IGF-I.
Chen J-W, Hojlund K, Beck-Nielsen H, Sandahl Christiansen J, Orskov H, Frystyk J. Free Rather than Total Circulating Insulin-Like Growth Factor-I Determines the Feedback on Growth Hormone Release in Normal Subjects. Journal of Clinical Endocrinology & Metabolism 2005;90(1):366-71. Free Rather than Total Circulating Insulin-Like Growth Factor-I Determines the Feedback on Growth Hormone Release in Normal Subjects
Pituitary GH secretion is feedback regulated by circulating IGF-I. However, it remains to be determined whether the feedback control is mediated through circulating free or total IGF-I. To study this, we compared the temporal changes in circulating levels of GH vs. free and total IGF-I during fasting.
Seventeen healthy normal-weight subjects (body mass index 23.4 ± 0.6 kg/m2) were studied during 80 h of fasting. Serum was assayed for GH every 3 h; total, free, and bioactive IGF-I, IGF binding protein (IGFBP)-1, -2, and -3 as well as IGFBP-1 bound IGF-I were assayed every morning.
During fasting, mean 24-h GH levels increased from 1.41 ± 0.20 to 3.01 ± 0.46 and 2.09 ± 0.30 μg/liter (d 1 vs. d 2 and 3; P < 0.03). After 24 h of fasting, free and bioactive IGF-I had decreased by 40 ± 5 and 17 ± 5%, respectively (P < 0.02), and both concentrations remained suppressed for the rest of the study. In contrast, total IGF-I remained unchanged until the end of d 3, at which levels were slightly reduced (P < 0.007). IGFBP-1 increased from 38 ± 2 to 137 ± 24, 212 ± 32, and 214 ± 22 μg/liter (d 1 vs. d 2, d 3, and end of d 3; P < 0.0001), and these changes closely paralleled those of IGFBP-1-bound IGF-I (P < 0.0001). IGFBP-2 increased only transiently at d 2 (P < 0.05), and IGFBP-3 remained unchanged. The increase in mean 24-h GH levels from d 1 to d 2 correlated inversely with the relative reduction in free IGF-I from d 1 to d 2 (r = −0.51; P = 0.04), i.e. the larger the reduction in free IGF-I, the larger the increase in GH. None of the other IGF-related parameters correlated with GH.
In conclusion, the temporal relationship between the increase in GH and the reduction in free IGF-I supports the hypothesis that circulating free IGF-I mediates the feedback regulation of GH secretion.
Brearley C, Priestley A, Leighton-Scott J, Christen M. Pharmacokinetics of recombinant human growth hormone administered by cool.click 2, a new needle-free device, compared with subcutaneous administration using a conventional syringe and needle. BMC Clin Pharmacol 2007;7:10. BMC Clinical Pharmacology | Full text | Pharmacokinetics of recombinant human growth hormone administered by cool.click (TM) 2, a new needle-free device, compared with subcutaneous administration using a conventional syringe and needle
BACKGROUND: Growth hormone (GH) is used to treat growth hormone deficiency (GHD, adult and paediatric), short bowel syndrome in patients on a specialized diet, HIV-associated wasting and, in children, growth failure due to a number of disorders including Turner's syndrome and chronic renal failure, and in children born small for gestational age. Different brands and generic forms of recombinant human growth hormone (r-hGH) are approved for varying indications in different countries. New ways of administering GH are required because the use of a needle and syringe or a device where a patient still has to insert the needle manually into the skin on a daily basis can lead to low adherence and sub-optimal treatment outcomes. The objective of this study was to assess the relative bioavailability of r-hGH (Saizen, Merck Serono) administered by a new needle-free device, cool.click 2, and a standard needle and syringe.
METHODS: The study was performed with 38 healthy volunteers who underwent pituitary somatotrope cell down-regulation using somatostatin, according to a randomized, two-period, two-sequence crossover design. Following subcutaneous administration of r-hGH using cool.click 2 or needle and syringe, pharmacokinetic parameters were analysed by non-compartmental methods. Bioequivalence was assessed based on log-transformed AUC and C(max) values.
RESULTS: The 90% confidence intervals for test/reference mean ratio of the plasma pharmacokinetic variables Cmax and AUC(0-inf) were 103.7-118.3 and 97.1-110.0, respectively, which is within the accepted bioequivalence range of 80-125%. r-hGH administered by cool.click 2 is, therefore, bioequivalent to administration by needle and syringe with respect to the rate and extent of GH exposure. Treatment using cool.click 2 was found to be well tolerated. With cool.click 2 the tmax was less (3.0 hours) than for needle and syringe delivery (4.5 hours), p = 0.002 (Friedman test), although this is unlikely to have any clinical implications.
CONCLUSION: These results demonstrate that cool.click 2 delivers subcutaneous r-hGH exposure that is bioequivalent to the conventional mode of injection. The new device has the additional advantage of being needle-free, and should help to increase patient adherence and achieve good therapeutic outcomes from r-hGH treatment.