Hypertrophy versus Hyperplasia

Science  30 Sep 1966:
Vol. 153, Issue 3744, pp. 1615-1620
DOI: 10.1126/science.153.3744.1615


Although all tissues and organs of the body are normally subject to the growth-regulating influences of functional demands, some are potentially capable of unlimited growth while others are not. This depends on whether hyperplasia of their functional units ceases prior to maturity or can continue throughout life. In the former case, further growth is limited by the extent to which hypertrophy can enhance physiological efficiency. Some of the body's most vitally essential organs (heart, brain, kidney, lung) lack the ability to make additional structural units in the adult and are therefore handicapped in compensating for the depreciations of advancing age. Theoretically, at least, other organs (glands, renewing tissues) possess unlimited powers of regeneration because they never lose the capacity (latent or expressed) for hyperplasia.

There is a strategy in the way growth mechanisms have evolved. It may be significant that the so-called "hypertrophic" organs lose the capability for hyperplasia, because not to do so might jeopardize their growth regulation. If size is determined by functional demands, then the latter must not operate continuously lest growth go on without interruption and lead to overproduction of functional units. Only renewing tissues can tolerate perpetual growth because they get rid of excess structures as fast as they are formed. Endocrine and exocrine glands are in most cases known to function discontinuously and are thus not in danger of being overstimulated. The heart, lungs, and kidneys (and brain?), however, must work incessantly. Were their functional units capable of hyperplasia and at the same time subject to control by functional demand, then overgrowth would seem to be inevitable. By giving up the potential for hyperplasia in favor of the necessity for constant function, these organs have adopted a strategy that enables them to become hypertrophic to a limited extent while doing their jobs efficiently.

It is a curious fact that the unrestricted proliferation of biological structures cannot occur at all levels of organization. The counterpart of cancer, which is a cellular phenomenon, does not exist among molecules or cytoplasmic organelles, nor is it known to occur at the histological level of organization. Even in organs made up of histological units of function and having the potential for unlimited hyperplasia (for example, liver, exocrine glands, thyroid, ovary), the population of functional units never exceeds the number needed to fulfil the physiological requirements of the body. Above and below the level of the cell, therefore, structures are not permitted to escape the constraints of functional demands which control their production. The fact that cells can occasionally do so when they become neoplastic may reveal as much as it conceals about the problem of growth regulation.