JOUR. D . D . VOLUME VII NOVEMBER, 1940 NUMBER 11

I. An Experimental Study of the Effect of the Pituitary on the Motility of the Gastro-lntestinal Tract

A Preliminary Reporr

By

SAMUEL MORRISON, M.D.t and

MAURICE FELDMAN, M.D.S BALTIMORE, MARYLAND

T the last meeting of this Association we reported some studies on the effect of the thyroid on

gastro-intestinal motility. In that communication (1) we recorded the acceleration of motility produced by thyroid medication in both normal and vagotomized dogs. We also pointed out that bilateral thyroidectomy had no immediate effect upon motility. Combined effects of vagotomy and thyroidectomy were the same as those of vagotomy alone and could be overcome by thyroid medication. This led us to believe that the effect of thyroid medication was independent of vagus continuity but later we found (2) that atropinization could annul this effect.

I t seemed opportune to utilize this same group of dogs, which we had observed repeatedly and therefore knew well so fa r as their responses were concerned, for a study of the action of the pituitary. There was also the thought that since the anterior lobe of the pi tui tary gland elaborates a thyrotropic principle, among several others, it might be possible to evaluate its action. As will be seen, the problem became so complex that we are reporting only certain phases of it at this time, even excluding studies on dogs with hypophysectomy alone, since so much of the work is still in progress and a more complete summary is in- tended later.

Cushing (3), in 1912, was among the first to show that total hypophysectomy in dogs was followed by rapid involution of the thyroid and yet contrary to current opinion the relationship of the anterior lobe of the pi tui tary to the thyroid gland has not been ex- tensively studied in man. In recent years, however, many investigators (4) have demonstrated that the anterior lobe of the pituitary contains a hormone which stimulates the thyroid gland. Nevertheless, the knowl- edge of hormones of the anterior lobe of the pituitary is as yet quite incomplete. Although a variety of fractions with supposedly specific functions have been prepared, much of their chemical natures is quite un- certain and their therapeutic uses, except in a few conditions, are still largely dependent on animal rather than clinical investigation. With reference to the di- gestive tract Collip (5) believes that the pituitary hormones are not essential for its functioning and this, he observes, is shown by the failure of hypo- physectomy to produce any well defined changes in

*From the Gastro-Enterological Division of the Depar tment of Medi- cine, Universi ty of Maryland, School of Medicine.

tAsslstant Professor of Gastro-Enterology. :~Assistant Professor of Gastro-Enterology. Note: This work was supported by the Julius Friedenwald Research

Fund. Presented before the American Gastro-Enterological Association, At-

lantic City, June I0, 1940.

digestive functions, an opinion which some believe is open to discussion. Such controversial opinions are partly responsible for the present investigation.

The present study of the effect of the pi tui tary upon the motility of the gastro-intestinal tract is limited to the following group of observations:

A. The effect of the administration of anterior lobe pituitary extract upon the gastro-intestinal mo- tility :

1. Of normal dogs. 2. Of the vagotomized-hypophysectomized dog. 3. Of vagotomized-thyroidectomized-hypophysecto-

mized dogs. 4. Of the thyroidectomized-hypophysectomized dog. B. The effect of the operations themselves: 1. Upon motility of the gastro-intestinal tract. 2. Upon gastric secretion. In other words, we have simply superimposed the

operation of hypophysectomy and the treatment with anterior pituitary lobe extract upon a group of standardized dogs.

In four normal dogs (average weight 8 kgs. each), anterior lobe pituitary extract was injected to a dosage of 30 cc. over a period of 20 days. X-ray studies were made to determine the effect of such treatment on the motility of the gastro-intestinal tract.

I t was found on repeated examinations that the stomach was completely empty in six hours and that the head of the barium meal was in the descending colon. In a series of eight dogs in which normal gastro-intestinal motility was studied, precisely the same findings were observed. It therefore follows that anterior pi tui tary lobe extract has no demonstrable or significant effect upon gastro-intestinal motility in the normal dog.

The vagotomized dog was hypophysectomized and after a three week recuperative period X-ray studies of the gastro-intestinal tract revealed a gastric re- tention with the barium scattered through both the small and large intestines. This picture exactly dupli- cated that of the animal af ter bilateral vagotomy alone. Six weeks after the pituitary operation a similar X-ray picture was observed. This dog was placed upon anterior lobe pituitary treatment for a period of three weeks. For one week the dog was given oral pituitary therapy (pituitary body anterior lobe, desic- cated) in a dosage of ~ gram daily and for two ad- ditional weeks increasing dosage of the extract was administered subcutaneously to a total dose of 21 cc.

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A six hour X-ray study made at this time revealed a gastric retention with the head of the barium meal in the distal colon. The latter picture did not differ significantly from that observed without pituitary therapy and without hypophysectomy.

In the two vagotomized-thyroidectomized-hypophy- sectomized a n i m a l s , roentgen studies made three weeks after the hypophysectomy revealed a gastric re- tention with most of the barium in the small intestines and a small amount in the large intestine. This X-ray picture was not significant since it usually results from the vagotomy alone. Five weeks after the pitui- ta ry operation there was still a large gastric retention with the barium scattered through both the small and large intestines. Increasing subcutaneous doses (to a total of 21 cc.) of anterior lobe pi tui tary extract were administered for two subsequent weeks to these two dogs. X-ray studies made at this time, i.e. a six hour examination, revealed a large gastric retention with most of the barium in the small bowel and a small amount of the colon. One dog was made ill by the pituitary treatment. The X-ray pictures in these two animals were similar to those observed in the animals which had a vagotomy alone.

In the remaining dog in which a thyroidectomy and later an hypophysectomy had been performed, several X-ray studies made prior to treatment showed in each instance a normal gastric emptying. Occasionally there was a small gastric residue, a variable finding, but the progress of the meal through the intestinal tract was normal. The administration of anterior lobe pituitary extract in the manner already described did not change this X-ray picture.

COMMENT It has been reported by others and can be verified

by any observer that hypophysectomy alone does not affect the m o t i l i t y of the gastro-intestinal tract. Though it must be admitted that in the presence of a vagotomy the effect of a superimposed hypophysectomy may not be apparent, the same cannot be said in the case of thyroidectomy. In the latter instance the effect of thyroidectomy is practically nil for clinically this dog had not developed myxedema and therefore any additional effect must be attributed to the hypophy- sectomy. However, the latter operation produced no demonstrable change in the roentgen-ray findings. Furthermore, the administration of adequate amounts of anterior pi tui tary lobe extract, orally or subcutane- ously or both, unlike thyroid medication, did not in any degree, affect the motility of the gastro-intestinal tract either in the normal or in the variously operated

dogs. More complete studies now in progress seem to bear out this impression.

Gastric test meals (50 cc. of 7% alcohol) made upon this series of hypophysectomized animals without gland treatment are tabulated below:

Free HC1 (One Hour Total

Dog Operation Extractions ) Acidity

Vagotomy-hypophysect omy

Thyroidectomy-hypophysectomy

Vagotomy-thyroideetomy-hyp ophy- sectomy

Vagotomy-thyroidectomy-hypophy- sectomy

50

62

38

52

74

76

56

74

These values may be considered within normal limits.

In this connection it is interesting to recall the re- port of Snapper (6) who observed five patients with insufficiency of the anterior lobe of the pi tui tary body and found an associated complete gastric achylia. The suggestion is made that a possible physiologic effect of the anterior lobe on gastric secretion may be im- plied. On the other hand, Waterman (7) examined the gastric contents of 192 hypophysectomized rats, in 27 per cent of which the stomach was found to be empty and no acid juice was secreted. However, if the stomachs of these animals were filled w i t h food, hydrochloric acid could always be demonstrated in the contents. Waterman concludes that although pituitary extracts may produce an increased gastric secretion, hypophysectomy is not necessarily followed by achylia gastrica in the animals mentioned.

CONCLUSIONS Though they may be modified by the more or less

indirect method of approach the following conclusions seem justifiable :

1. Gastro-intestinal motility in normal dogs is not affected by the subcutaneous administration of an- terior lobe pituitary extract therapy.

2. Gastro-intestinal m o t i l i t y is not affected by hypophysectomy.

3. The administration of anterior lobe pituitary gland to these hypophysectomized animals had no effect upon gastro-intestinal motility.

4. Gastric test meals in these operated but other- wise untreated dogs revealed normal secretory values.

Note: The preparation of the pituitary materials used in these studies is discussed in the final note of Section 2.

R E F E R E N C E S 1. Morrison, S. and Feldman, M. : An Experimental Study of the Thyrotropic Extract in Subjects with Low Basal Metabolic Rates.

Effect of the Thyroid on the Motility of the Gastro-Intestinal Qur J. of Med., 8:195, 1939. Tract . Am. J. D/g. D/s., 6:549, Oct., 1939. 5. Collip, J . B. : The Endocrine in Relation to the Gastro-Intestinal

2. Morrison and Feldman, M,: The Effect of Atropine on the Gastro- Tract . Transactions Am. Gc~stro-Ent. Assn., p. 109, 1938. Intestinal Trac t Following Thyroid Medication. To be published 6. Snapper, I. : Relation Between Anterior Pi tui tary Insufficiency and in Endocrinology. Function of Stomach and Bone Marrow. Nederl. Tigdschr. v.

3. Cushing, H . : The Pi tui tary Body and Its Disorders. J. B. Lippin- geneesk., 81:265, 1937. cott Co., Philadelphia and London, 1912. 7. Waterman, L . : Hydrochloric Acid Secretion in the Stomach of

4. SharpeyoSchafer, E. P. and Schrire, I . : The Effect of Pi tui tary Hypophysectomized Rats. Acta. Brcv. Neerland, 8:182, 1938.