22 



Ch. M. Lapiere 



temperature of the body all the collagen seems to be organized in fibers. The extrac- 

 tion procedure removes some collagen from this pool. 



Whether the extractable collagen arises from fibers of different age or from out- 

 side layers around different fibers is not yet known. Some autoradiographic studies of 



Proline 



Hypro 



le extracted collagen; NM the neut 

 A the acid one and I the insoluble. D refers to degradatio 



ic extracted fraction; 



Hay and Revel (1963) show that the newly formed collagen is concentrated in 

 regions of different metabolic activity. According to Tanzer and Hunt (1964), in 

 the lathyrltic chick embryo the newly formed bone collagen is organized In fibrillar 

 aggregates which can be solubilized. Following Jackson and Bentley (1960) it seems 

 reasonable to admit a dual origin of the salt extracted collagen. It could arise from 

 newly formed fibrils and from the outside layer of previously deposited collagenous 

 elements which are increasing in size by accretion of newly synthesized molecules. In 

 tadpole tissues, the extracellular collagen can be fractionated in different pools. The 

 proposed composition of these fractions is summarized at the bottom of Fig. 1. For 

 each of them, in terms of incorporation of the labelled precursor, the "1" form is 

 labelled much faster and more heavily than the "2" form. 



The isotonic saline extract (N) contains the newly formed collagen (Nj) but also, 

 mainly in remodelling tissues, larger amounts of a pre-existent unlabelled collagen 

 (N2). The hypertonic saline (NM) is also composed of two pools, one of which (NMj) 

 becomes labelled later than its proposed precursor (Nj). It has to be distinguished 

 from another pool (NMg) larger in size but labelled much later. The more organized 

 collagen which is not extractable under our experimental conditions, (I.,), comes 

 next in the metabolic chain. It has to be differentiated from the very small but highly 

 radioactive collagen bound to the microsomes in cells (IJ which is not extractable. 

 The acid extractable collagen (A) always has the lowest specific activity among all the 

 fractions. It might derive from the I2 pool. Although the proposed scheme is based 

 on the analysis of isotope dilution experiments, it remains partly hypothetical because 

 it has not yet been possible to separate the different pools of molecules forming each 

 fraction. However it gives an indication that the structured collagen fibers in the 

 connective tissues are organized according to some factors related to aging and to the 

 metabolic activity of the tissue. This metabolic behaviour of the extracellular collagen 

 is different in soft connective tissues which are in a steady state and those which are 

 remodelling. In steady state tissues, a short metabolic pathway seems to be pre- 



