Sites and Mode of Action of Growth Hormone 253 



Three children given 0.71 g./kg. glucose at 6.0 o' clock in the evening showed an 

 immediate abolition of hormone secretion. Four children given the same dose of 

 glucose at 7.0 o' clock in the morning (Fig. 4) showed no measurable growth hormone 

 during the following three hours. After this period a secondary rise occurred. Plasma 

 N.E.F.A. was low during the first three hours, then rose steadily till the end of the 

 six hour study period. 



Lastly, during elective surgical operations, irrespective of the time of day, plasma 

 growth hormone levels rose rapidly to heights comparable to, or higher than, the 

 peaks found at rest. 



Discussion 



Growth hormone ultimately influences growth by an effect on the stem cells in 

 the cartilages of the epiphysis. How this action occurs is not clear. 



In nine of the children submitted to diurnal studies G. H. was detected in 

 72 of 142 plasma samples [compared to only 8 of 41 samples from a comparable 

 adult series (Hunter et ai, in press)]. The mean level in the children was 

 4.28 ± 7.14 S.D.//mg./ml. and the range was to 53 ,«mg./ml. (compared to a mean 

 of 0.52 ± 0.46 S.D.//mg./ml. and a range of 0—2.7 ,//mg./ml. in the adults). This 

 study reveals that the difference between adults and children is due to much higher 

 and more frequent peaks, but not due to a continuously elevated secretion, in the 

 children. This finding emphasises the futility of attempting to estimate growth 

 hormone status from a single randon sample. 



Before 11 of 30 meals high levels of hormone were recorded. After the meal the 

 levels fell to base line in all cases except one where the child vomited soon after his 

 supper. A complex situation was simplified by the glucose test meal studies. For three 

 hours following the intake of glucose (whether during the morning or the evening) 

 the G. H. levels remained at the base line. A secondary rise occurred during the 

 second three hour period (which tends to correspond to the time preceding the next 

 meal). At the time the hormone level rises plasma N.E.F.A. levels also rise. This is 

 a reflexion of the hormone's known fat mobilisation action. 



At least during the daytime the pattern of secretion is similar in children and 

 adults and appears to be related to energy requirements. (G. H. providing N.E.F.A. 

 as energy substrate.) 



High night-time secretion was a consistent finding in adequately tested cases. But 

 even during this period a consistent measurable level of G. H. does not occur. Total 

 night secretion is much higher than that which occurs during the day. 



Anaesthesia and surgery regularly evoked G. H. secretion. Many factors are at 

 play under these conditions but the demands of growth are presumably not involved. 



It would now be desirable to relate these actions of the hormone to its growth 

 promoting function. So far it has not been possible to relate plasma levels directly 

 to skeletal growth. Acute administration of the hormone, as has now been well 

 confirmed, is followed by (i) increase in plasma N.E.F.A. due to lipolysis of depot 

 fat (Raben and Hollenberg, 1959) and by (ii) increased amino acid uptake by 

 tissues (KosTYO and Engel, 1960; Peckham and Knobil, 1960). Utilisation of fatty 

 acid for energy demands can spare carbohydrate and proteins. These factors would 

 produce conditions conducive to tissue growth. 



