GREGORY PINCUS 



fects in practically every known disease have multiplied. At the 

 moment it is hard to see the forest for the trees, but a concept of 

 "regulatory" therapy appears dimly. The most vocal protago- 

 nist of such a concept has been Professor Hans Selye, whose 

 various publications on "diseases of adaptation" suggest a dis- 

 turbance of the normal pituitary-adrenal relationship as one 

 etiologic factor in a great variety of diseases (14). It is impos- 

 sible to summarize adequately the voluminous discussion and the 

 shifts and changes which have marked this general theory. The 

 endocrine basis has been a notion of imbalance between mineralo- 

 corticoid and glycocorticoid hormones of the adrenal cortex 

 which in turn involves imbalances in mineralocorticotrophic and 

 glycocorticotrophic pituitary hormones. Thus far no mineralo- 

 corticotrophin has been established as a distinct entity, al- 

 though Selye believes that pituitary growth hormone serves that 

 function. ACTH acts as the glycocorticotrophin. The theory 

 demands that continued stress induces an alteration in adreno- 

 cortical output of such a nature that mineralocorticoids tend 

 under chronic stress to preponderate among the secretory 

 products. Certain recent findings are worth mentioning. 

 First of all, the discovery of aldosterone as an extremely potent 

 adrenal mineralocorticoid (15) suggests that this substance may 

 be the prophlogistic adrenal hormone. Secondly, the excretion 

 of aldosterone-like sodium-retaining activity in human urine 

 appears to be increased by growth hormone administration and 

 unaffected by ACTH administration (17). Thirdly, chronic 

 ACTH administration, the presumed equivalent of chronic 

 stress, significantly alters the nature of adrenocortical secretion; 

 in the rabbit, primarily a secretor of corticosterone, chronic 

 ACTH treatment tends to increase Cortisol and decrease corti- 

 costerone secretion (8). Since corticosterone is more of a 

 mineralocorticoid than Cortisol (the typical glycocorticoid), 

 ACTH, in the rabbit at least, tends to alter adrenocortical se- 

 cretion toward prophlogistic hormone output. A detailed dem- 

 onstration of the nature of aldosterone biogenesis and of the 

 nature of adrenal secretion in chronic stress is clearly needed. 



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