250 W. M. RiGAL, W. M. Hunter 



Sites and Mode of Action of Growth Hormone 



W. M. RiGAL, W. M. Hunter 



Department of Orthopaedic Surgery, University of Edinburgh, Edinburgh, Scotland; 

 Medical Research Council, Clinical Endocrinology Research Unit, University of Edinburgh, 



Edinburgh, Scotland 



Towards the end of puberty a profound change occurs in bone. This is so striking 

 that it might, for want of a better term, be called "bone puberty". There is as yet no 

 clear correlation between this event and chronological age, cessation of growth, 

 sexual maturation or bone age. Before bone puberty, bone has great reparative power 

 and is in some respects plastic. For example, fracture union is rapid and non-union is 

 rare; a tibia or femur can be lengthened four inches (10 cm.) or more following a 

 simple transverse osteotomy and reconstitution of the defect occurs rapidly; the 

 curve in idiopathic (spinal) scoliosis continues to progress; and imbalanced muscle 

 pull produces bone malalignment. 



After bone puberty the reparative power of the tissue is much reduced and its 

 apparent plasticity disappears. Anterior pituitary growth hormone (G. H.) presum- 

 ably plays some part in this alteration that occurs in bone tissues (Koskinen, 1965). 

 This assumption has prompted an investigation into the sites of action of the hormone 

 and its activity during puberty. 



Sites of action 



In young growing rabbits 5*'/o of the cells of the germinal zone (zone one) of the 

 epiphyseal growth cartilage are generatively active. Within the articular cartilage, 

 and also in the anlage cartilage while it still persists, a single line of cells exhibits 

 reproductive activity (Rigal, 1962). Growth hormone, in the intact animal, exerts 

 its greatest influence on growth by stimulating these stem cell zones (Rigal, 1964). 

 Injection of excess growth hormone results in 25''/o to 50''/o of the germinal zone cells 

 becoming generatively active, and, in the articular and anlage cartilage the two 

 narrow lines of widely spaced active cells become continuous and several cells wide. 

 A similar effect could not be demonstrated in vitro. 



Mode of action 



Methods 

 The radio-immuno-electrophoretic assay of Hunter and Greenwood (1964) has 

 been used to measure plasma human growth hormone under varying conditions in 

 children between the ages of 9 years and 15 years who were normal from the endo- 

 crine point of view. 



1. Diurnal studies: the children were confined to bed and plasma samples taken at 

 hourly intervals during day-light hours and at two hour intervals during sleep at 

 night. 



2. Nocturnal studies: samples were taken at half-hourly intervals during a 14 

 hour period which included the whole night. 



'■■ These investigations arc supported b}' British Medical Research Council Grant No. G. 963134. 



