From each portion of the gland (to stick to the accepted nomenclature of speaking of the two glands as one) an active substance has been isolated. Robertson, an American chemist, separated from the anterior lobe a substance soluble in the fat solvents, like ether and gasoline, which he christened tethelin. But P.E. Smith has shown that the active material is soluble neither in boiling water nor in boiling alcohol, the typical fat solvent. A number of facts favor the idea of the anterior lobe cells as stimulants of growth of bone and connecting and supporting tissues generally. From the posterior lobe, pituitrin, believed its internal secretion, has been obtained in solution.
Pituitrin is a substance of many marvelous functions. In general, it controls the tone of the tissues, of involuntary or smooth muscle fibres of the blood vessels and the contractile organs of the body like the intestines, the bladder and uterus. When injected, it will slowly raise the blood pressure and keep it raised for some time, and will increase the flow of urine from the kidneys and of milk from the breasts. It will also cause an intense continued contraction of the bladder and the uterus. It is also said to control the salt content of the blood upon which its electrical conductivity and other properties depend. Normally, there is a certain fixed ratio of the salts in the blood, which keeps them like the ratio in sea-water. Again, we have an example of the curious atavism of the internal secretions. The thyroid, remember, keeps the iodine concentration of the blood like that of the ocean, our original habitat. Pituitrin likewise does its part to maintain our internal environment as near as possible to what was once the surrounding medium. A substance somewhat similar has been found in the skin glands of toads.
The extraordinarily well protected position of the pituitary, its persistence throughout life, and its abundant blood supply, emphasize its vital importance. No other gland of internal secretion can adequately substitute for it. Complete expiration means death, in two or three days, with a peculiar lethargy, unsteadiness of gait and loss of appetite, emaciation, and a fall of temperature, so that the animal becomes cold-blooded, its temperature the same as that of the atmosphere it occupies. If only part of the anterior lobe is taken away, there occurs a remarkable degeneration of the individual. The degeneration is not a mucinous infiltration of the skin and the internal organs which occurs with thyroid deprivation, but a fatty degeneration, with a tendency to inversion of sex. A singular somnolence, a dry skin, loss of hair, a dull mentality, sometimes epilepsy, and a noticeable craving for and tolerance of sweets appear. These are but a few of the observations obtained in experimental sub-pituitarism, that is, underaction or insufficient secretion of the pituitary, produced by removing part of the anterior gland.
If such an experimental sub-pituitarism is started in infancy, for instance in puppies, there is a cessation, or marked hindering and slowing of growth. That is, dwarfs are artificially created. Apropos, pathologists have shown that in several true human dwarfs the gland is rudimentary or inadequate. All of which goes hand in hand with the evidence that the skeleton stands directly under the domination of the pituitary.
REGULATOR OF ORGANIC RHYTHMS
There are certain other singular by-effects of the gland in its relation to the periodic phenomena of the organism like hibernation, sleep, and the critical sex epochs of both sexes. In hibernation, or winter sleep, the animal in cold weather passes into a cataleptic state in which it continues to breathe, more deeply but more slowly than when awake, but shows no other signs of consciousness or life. A lowered blood pressure and a marked insensitivity to painful and emotional stimuli go with it. There is a preliminary storage of starch in the liver, and of fat throughout the fat depots of the body. These are so like what happens after part of the pituitary is removed, that a comparison of the two becomes inevitable. Common to both conditions is a drop in the rate of tissue combustion or metabolism, which can be relieved by injection of an extract of the pituitary, a rise of temperature occuring simultaneously. Moreover, examination of the glands of internal secretion of hibernating species, like the woodchuck, during the period of hibernation, shows changes in all of them, but most marked in the pituitary, the shrunken cells staining as if they too were asleep, or in a resting stage. The characteristic alive qualities of these cells return, without relation to food or climate, when the animal comes to in the spring, at the vernal equinox. Hibernation may, perhaps, be put down to a seasonal wave of inactivity of the pituitary gland.
Now winter sleep may be looked upon as an exaggeration of ordinary night sleep, the latter differing from the former only in its brevity. In the natural sleep of non-hibernating species there occurs, too, a fall in temperature. Moreover, they all, even man, have a certain capacity for winter sleep, as the experiences of travellers and explorers in the arctic regions indicate. In certain parts of Russia, where there is a scarcity of food during the winter months, the peasants pass weeks at a time in a somnolent state, arousing once a day for a scant meal. Just as the sex glands influence the body and mind profoundly with a certain cyclic periodicity of activity and inactivity (rut, heat, menstrual period and so on), which has been demonstrated to have a very close functional relationship with the pituitary, so sleep and hibernation will bear interpretation as products of a temporary dormancy of the same gland. We have, then, to set up in the place of Morpheus and Apollo, the new gods of the internal secretion of a chemical-making bit of the brain, as an explanation of the rhythms of sleep and wakefulness.
There are individuals who go about outside of hospital walls, quasi-normally, who are semi-hibernators or partial hibernators, and who are really in a state of subpituitarism. They are people who may have something wrong or inferior with their pituitary, but not to the extent of interference with their daily life. They go about with their type stamped upon them for the seeing eye. The classical type is obese, with fat distributed everywhere, but more so in the lower abdomen and the lower extremities. They are slow and dull, and sexually inactive, often impotent. They are sometimes tall, but most often dwarfish, and may be subject to epileptic seizures. They recall the picture of what happens to young dogs partially deprived of the pituitary. Dickens delivered a perfect likeness of an extreme degree of the condition in the Fat Boy of the "Pickwick Papers," whose employment with Mr. Wardle consisted in alternate sleeping and eating.
WHEN THE PITUITARY OVERACTS
All grades of overaction of the pituitary exist. Then its peculiar power to act as a stimulant to the growth of bone and the soft supporting and connecting tissues like tendons and ligaments comes into play. If the overaction or excess of secretion begins in childhood or adolescence, that is, before puberty, there results a great elongation of the bones, so that a giant is the consequence. Now giants have always appealed to the imagination of the little man, and have had all kinds of wonderful abilities ascribed to them by him. The giants and ogres of folk-lore and fairy tales are favored with the most extraordinary mental advantages. Direct and analytic acquaintance with the giants of our own day, as well as a probing of their conduct in the past, has shown that normal giants—persons of exceptional size free from physical or mental deformities—are rare. There are people with hyper-pituitarism who exhibit the highest mental powers. In them is an increased activity of the posterior lobe in association with enlargement and hyperfunction of the anterior, overgrowth is not so marked, and the individual is lean and mentally acute. But the ordinary giant is one in whom there is degeneration of the pituitary after too much action of the anterior and too little of the posterior glands. A tumor or disease process in the gland is most often responsible.