Dl-XEMBER I, 1923] 



NA TURE 



795 



Hormones.^ 



Bv Prof. E. H. Starling, C.M.G., F.R.S. 



IX the dedication to his work, Harvey compares 

 the heart to the sovereign king, and throughout 

 he continually recurs to what we should now describe 

 as the " integrative function " of this organ. In 

 virtue of the circulation which it maintains, all parts 

 of the body are bathed in a common medium from 

 which each cell can pick up whatever it requires for 

 its needs, while giving off in return the products of 

 its activity. In this way each cell works for all others 

 — the lungs supply every part with oxygen and turn 

 out the carbon dioxide which it produces, the ali- 

 mentary canal digests and absorbs for all, while the 

 kidneys are the common means of excretion of the 

 soluble waste products of the body. Changes in any 

 one organ may therefore affect the nutrition and 

 function of all other organs, which are thus all members 

 one of another. But, in addition to enabling this 

 community of goods, the circulation affords oppor- 

 tunity for a more private intercourse between two 

 or at any rate a limited number of distant organs. 



It is now eighteen years since I directed attention 

 to the chemical messengers or hormones which are 

 employed by the body for this purpose. As an illustra- 

 tion of the method by which they work, I adduced 

 the example of carbonic acid gas, which is the product 

 of all cellular activity and at the same time has a 

 specific excitatory effect on the respiratory centre, 

 so that the respiratory movements keep pace with 

 the needs of the whole body for oxygen. The typical 

 hormone, however, is a drug-like body of definite 

 chemical composition, which in a few cases is actually 

 known, so that the substance has been synthesised 

 outside the body. It is more or less diffusible, and 

 may even withstand without alteration the tempera- 

 ture of boiling water. It is generally easily oxidisable 

 in a neutral or alkaline medium, so that after its 

 production it does not remain long in the blood ; it 

 delivers its message and is then destroyed. Each 

 specific hormone is manufactured by a group of cells 

 and turned into the blood, in which it travels to all 

 parts of the body, but excites definite reactions in 

 one or a limited number of distant organs. The 

 production and action of these substaaces are con- 

 tinually going on in the normal animal. They are 

 neces.sary to health, and their production in excess 

 or in deficit gives rise to disease and maybe to death. 



Typical of all hormones is secretin, a substance 

 produced in the epithelial cells lining the upper part 

 of the small intestine when these come in contact 

 with weak acid, so that it is set free in normal cir- 

 cumstances by the passage of the acid chyme from 

 the stomach into the duodenum. Directly it is pro- 

 duced it is absorbed into the blood and travels round 

 to the pancreas, to the liver, and to the intestinal 

 glands, in all of which it excites secretion. By means 

 of this chemical reflex the arrival of the products of 

 gastric digestion in the small intestine evokes within 

 a couple of minutes the secretion of the three juices 

 the co-operation of which is necessary for completing 

 the work of digestion and solution of the food, already 



' From tlip Harvcian Oration, cntitlpd " The Wisdom of the Body," 

 (lelivorcd f)ofore the Royal College of Physicians of London on St. Luke's 

 Day, ()r,tol)tr i«. 



NO. 2822, VOL. I 12] 



begun in the stomach. It is probable that this mechan- 

 ism is but one of a whole chain of chemical reflexes 

 responsible for the orderly progression of the various 

 stages in the digestion of food. 



These hormones may apparently be formed by any 

 kind of tissue. In many cases a gland which has, 

 in the evolutionary history of the race, poured its 

 secretion by a duct into the alimentary canal or on 

 to the exterior, loses its duct and becomes a ductless 

 gland, the secretion being now transferred either 

 immediately or through the lymphatics into the blood 

 stream. In either case these chemical messengers may 

 be formed from masses of cells which have at no time 

 had a glandular structure and may be modified 

 nervous tissue, germinal tissue, or some part of the 

 mesoblast. 



As a type of the ductless gland derived from one 

 with an external secretion the most familiar example 

 is the thyroid. The physiological action of its internal 

 secretion and the morbid results of its excess or 

 deficiency, affecting tissue growth and development, 

 metabolism, and mentality, are familiar to all. In 

 recent years the active substance has been actually 

 isolated, and its constitution determined, by Kendal, 

 who has shown that it is an iodine derivative of an 

 amino-acid, tryptophane. It seems almost a fairy 

 tale that such widespread results, affecting every aspect 

 of a man's life, should be conditioned by the presence 

 or absence in the body of infinitesimal quantities of 

 a substance which by its formula does not seem to 

 stand out from the thousands of other substances 

 with which organic chemistry has made us familiar. 



Although we do not yet know their constitution, the 

 chemical messengers associated with the reproductive 

 organs are possibly even more marvellous in the 

 influence they exert on the different parts and functions 

 of the body. The effects of castration have been the 

 subject of observation almost from the beginnings 

 of civilisation, but it is only during the last few years 

 that definite proof has been brought forward showing 

 that these effects are due to the removal of chemical 

 messengers normally produced in the testes. The 

 whole differentiation of sex, and the formation of 

 secondary sexual characters, are determined by the 

 circulation in the blood of chemical substances pro- 

 duced either in the germ cells themselves or, as seems 

 more probable, in the interstitial cells of the testis 

 and ovary, which themselves are probably derived 

 from the germ cells of the embryo. Thus it is possible 

 by operating at an early age to transfer male into 

 female and "vice versa. Remov^al of the ovaries from 

 a hen causes the assumption of male plumage ; the 

 removal from a young cock of the testes and their 

 replacement by the implantation of ovaries cause a 

 disappearance of the comb and the assumption of 

 the plumage of the hen. Each animal as concerns 

 its general build and colour has a neutral form which, 

 as has been shown by Pezard, results from the extirpa- 

 tion of either testes or ovaries. In fowls the neutral 

 form, as judged by the plumage, approximates the 

 male, whereas in sheep the neutral form resembles 

 the female. There is no question that, by the 



