Acid Extract Of Anterior Pituitary Research Articles

Partial characterization of immunoreactive substance P in the rat pituitary gland

Two distinct carboxy-terminus-directed anti-substance P (SP) sera (R-1C and R-6G) were used to characterize immunoreactive SP (I-SP) in acetic acid extracts of anterior pituitary (AP) and posterior pituitary (PP) glands of adult male rats. The tissue concentrations of I-SP measured by R-1C and R-6G were comparable. The contents of I-SP were 600–1150 pg/AP and 25–52 pg/PP. I-luteinizing hormone releasing hormone and I-somatostatin (I-SOM) were undetectable in AP extracts, but PP extracts contained the equivalents of 325–785 pg I-SOM/gland. Serial dilutions of AP and PP extracts produced displacement curves with both SP antisera that were parallel to the respective synthetic SP standard and hypothalamic extract displacement curves. Gel filtrations of AP and PP extracts on a Sephadex G-25 column produced I-SP peaks eluting in the same fractions as synthetic SP and hypothalamic I-SP. However, the AP I-SP profile also revealed a side peak migrating between the void volume and the major I-SP peak. Neither immunoreactive species in the AP extract were eliminated when eluted with 6.0 M guanidine HCl, a strong denaturing agent. In vitro incubation of paired anterior hemipituitaries for 30 min in the presence of a 56 mM K + concentration resulted in a significant (p<.0001), 25-fold increase in the release of I-SP into the incubation medium above the mean control value. Radiofrequency lesions placed in the median eminence-arcuate region of male rats caused a significant (p<.001) reduction of I-SP in both the AP and PP. These reductions were inversely related to the plasma prolactin values. The elevation in plasma prolactin was taken as an index of completeness of lesions. We conclude that: 1) the rat pituitary contains I-SP as assessed by its immunologic and chromatographic behavior, 2) K + depolarization is a potent stimulator of the release of AP I-SP in vitro , 3) the ME-arcuate region is important for the maintenance of pituitary I-SP levels in the rat.

The subcutaneous assay of corticotrophin A.

Since the introduction of corticotrophin (ACTH) into therapy in 1949 the hormone has usually been assayed by the ascorbic acid depletion method of Sayers et al. (1948), in which the fall in the concentration of ascorbic acid in the adrenals of hypophysectomized rats is a linear function of the logarithm of the dose ACTH, given intravenously. In therapy, however, corticotrophin is, as a rule, given subcutaneously or intramuscularly and only occasionally intravenously as a continuous infusion. In recent years clinical and experimental observations were made which demonstrated that the expected potency of ACTH-preparations did not always equal their clinical effect, when injected extravascularly, i. e. subcutaneously or intramuscularly. The therapeutic value of corticotrophin preparations obtained by different chemical procedures varied from 25 % to about 300 % of that expected from the determination of potency by the ascorbic acid depletion method. However, if used for continuous intravenous infusion, no variation in the clinical effect from the labelled potency greater than that within the error of the assay itself could be observed. These findings are extensively discussed by Wolfson (1953) and Fisher et al. (1953). Wolfson distinguishes three main types of corticotrophin: Crude corticotrophin (the first international corticotrophin standard La-l-A; the U. S. P. corticotrophin reference standard), which chemically is a glacial acetic acid extract of anterior pituitary of mammals. Corticotrophin A (ACTX, purified corticotrophin, high-potency corticotrophin, Type I-purified ACTH of Thompson and Fisher), which chemically is crude corticotrophin purified by adsorption on oxycellulose and subjected to little or no acid or peptic hydrolysis. Corticotrophin B (Actide corticotrophin), which is prepared by the use of acid or peptic hydrolysis or both.

Morphology of Bacillus of Rat Leprosy.

ConclusionsInjections of acid extract of anterior pituitary of cattle have a stimulating effect on the growth of cartilage and bone of growing guinea pigs. The various layers of the cartilage cells become hypertrophie and hyperplastic, and are subsequently quickly calcined and replaced by bone. The epiphyseal line undergoes, therefor, premature closure under the influence of the extract.

Is Ant. Pituitary Hormone Demonstrable in Urine of Graves Disease, in Urine of Guinea Pigs Injected With Ant. Pituitary Extract?

Loeb and Bassett1 have shown that an acid extract of cattle anterior pituitary produces hypertrophy of the thyroid gland of guinea pigs. They noted that this experimentally produced hypertrophy characterized by an enlargement of the acinar cells, softening and absorption of colloid, and an irregular and often slit-like shape of the acini, and by the formation of papillary ingrowths into the acini resembles the pathological change in the thyroid gland in Graves disease. In a series of papers from this laboratory this similarity between the effects produced by the injection of extracts of the anterior pituitary gland of cattle and the symptoms of Graves disease has been further emphasized. Loeb and Friedman2 have produced exophthalmos in guinea pigs by repeated intraperitoneal injections of acid extract of the anterior pituitary. Siebert3 showed that this extract produced a rise in metabolism which was counteracted by the administration of potassium iodide, observations which accorded with the depressing ef...

Effect of Acid Extract of Anterior Pituitary on Heart Rate, and Nervous Irritability of Guinea Pigs.

It has been observed that the injection of acid extract of cattle anterior pituitary produces in guinea pigs a condition comparable to that seen in Graves'disease in human beings. Loeb has found a marked hypertrophy of the thyroid gland with diminution in the amount of colloid and a marked increase in the number of mitoses in the epithelial cells. Under the action of this substance the animals lose weight, and Siebert has shown that there is an increase in their metabolic rate. Other effects corresponding to conditions found in Graves'disease have been established in subsequent investigations carried out in this laboratory. Inasmuch as tachycardia and nervous irritability are very prominent symptoms of Graves'disease in man it was of interest to study the effect of this extract of anterior pituitary on the heart rate and the reflex irritability of guinea pigs. Cursory observations of Loeb seemed to indicate that such an effect might possibly exist. Twelve young male guinea pigs, approximately 200 gm. each, were chosen and normal records were obtained under a standard procedure using the electrocardiograph (lead one) to record the cardiac pulsations. Daily injections of 1 cc. of the acid extract were given to each of 6 guinea pigs, 3 of which had been thyroidectomized. The remaining 6 guinea pigs, 3 of which had been thyroidectomized, were used as controls, and were not injected. Records of the heart rate of all the animals were obtained on the 2nd, 4th, 9th, 11th, 16th, and 18th days. The heart rate of every animal in the group of injected non-thyroidectomized animals was faster on each occasion, after the second day of the injections, than that of any of the animals in the other groups.

Exophthalmos Produced by Injections of Acid Extract of Anterior Pituitary Gland of Cattle

In former investigations1 we observed that by injections of acid and alkali extracts of anterior pituitary of cattle, it was possible to produce in the guinea pig changes in the thyroid gland identical with those in very pronounced cases of Graves' disease in man, namely, a marked hypertrophy and hyperplasia of the acinus cells, softening and absorption of colloid and irregular shape of the acini, associated often with an almost complete disappearance of the lumen of the acinus. There was also a loss of weight induced by these changes which indicated an hyperactivity of the gland. Silberberg found that administration of KI to a certain extent inhibited these changes. This corresponds to the action of this substance in Graves' disease. Siebert noted a marked rise of the basal metabolism in guinea pigs under the influence of acid or alkali extracts and more recently found that simultaneous administration of KI tends to counteract the effect on basal metabolism. Closs, Loeb and MacKay1 found the changes in t...

Long Continued Injections of Acid Extract of Anterior Pituitary on Thyroid Gland and Sex Organs.

In former experiments on the effects of the injection of acid extract of cattle anterior pituitary on the thyroid gland of guinea pigs, we had found indications that these effects did not increase with continued injections. To determine the effects of long continued administration, a considerable number of young guinea pigs were given daily injections of anterior pituitary extract over a long period of time. Excluding those animals which were examined within the first 6 weeks after the beginning of the experiment, 10 guinea pigs received injections during a period of time varying between 47 and 74 days. The individual amounts injected daily varied between 1 cc. and 3 cc. of the extract. In some cases a few initial doses of 1/2 cc. were given. The total amounts injected ranged between 47 and 135 cc. The initial weights of the individual guinea pigs were between 185 and 205 gm. except one animal weighing 230 gm. There was a great difference between the weights reached at the end of the experiment. Some animals had gained considerably, while others remained unchanged. The microscopic examination of the organs showed that the severity of the effects of extract did not correspond to the amount injected. The animals evidently varied greatly in resistance. The resistant animals showed the least changes in their organs and these gained most rapidly in weight, while the most susceptible ones showed the greatest changes in their thyroid and sex organs, and did not gain as much or as rapidly in weight as the others. The former group became most readily adapted even to increasing doses of the extract. Thus those animals receiving the largest daily doses gained most in weight and their thyroid and sex organs showed the least change from normal or no change at all.

Effect of Acid Extract of Anterior Pituitary on Iodine Content of Blood and Thyroid in Guinea Pigs.

Loeb, Bassett and Friedman, Siebert and Smith, and Martin Silberberg1, 2, 3, 4, 5 have shown that injections of acid extract of cattle anterior pituitary produce changes in the guinea pig which bear close resemblance to the changes found in man in cases of Graves disease, as far as the structure of the thyroid gland, the behavior of the colloid, the changes in weight, as well as in the basal metabolism and the effect of KI in this condition are concerned. Lunde, Closs and Wulfert6 have shown that the acetone insoluble or globulin-iodine fraction of the thyroid gland of toxic goiters is both absolutely and relatively decreased, while the total blood iodine concentration has been found by Lunde, Closs, Pedersen,7, 8 and others9, 10 to be increased. There is reason for assuming that an increased elimination of the thyroid hormone from the gland into the circulation takes place in Graves disease. We wished to determine whether similar changes in the iodine distribution occur in the guinea pig under the influe...

Changes in Weight of Thyroid Gland of Guinea Pigs Under the Influence of Acid Extract of Anterior Pituitary.

Loeb, Bassett, and Hilda Friedman1, 2, 3 have shown that intraperitoneal injections of acid or alkali extracts of the anterior pituitary of cattle cause in the guinea pig a remarkable hypertrophy and hyperplasia of the thyroid gland associated with liquefaction and absorption of colloid. Martin Silberberg4 has studied the combined effect of KI and this extract on the thyroid gland and W. J. Siebert5 has determined the effect of various preparations of the anterior pituitary gland on the basal metabolism under various conditions. In our former investigations we used as a criterion of hypertrophy the microscopic changes in the thyroid gland after anterior pituitary injections. The thyroid glands of the injected animals appeared distinctly larger than the normal thyroids.We sought to determine the changes in weight of the thyroid glands produced by these preparations, in order to obtain quantitative data as to the intensity of the hypertrophy and hyperplasia. We carried out 3 experiments, the results of whic...

Further Investigations Concerning the Stimulating Effect of Anterior Pituitary Gland Preparation on the Thyroid Gland.

We have shown that while feeding of Armour's tablets of anterior pituitary has an inhibiting effect on the activity of the thyroid gland as indicated by the structural changes it induces, injections of acid or alkaline extracts of anterior pituitary prepared in our own laboratory from cattle gland have a very markedly stimulating effect, comparable to that characteristic of the thyroid in typical Graves'disease. We furthermore compared with the effects of the extracts, the effects of inoculation of anterior pituitary gland substance as such, obtained from guinea pig, rabbit, or cattle. These investigations suggested the conclusion that there are apparently several active substances in the anterior pituitary and that the substance responsible for the growth of the ovarian follicle and ovulation is not identical with the substance responsible for the hypertrophy of the thyroid gland, but that the latter seems to be identical with the substance which causes the production of interstitial gland and of pseudolutein bodies in the ovary of the guinea pig. Silberberg has shown that if acid extract of anterior pituitary and KI, both of which given singly stimulate the thyroid gland, are administered simultaneously, not only is there a lack of summation of the stimulating effects exerted by these substances, but a diminution of the hypertrophy which otherwise would have been caused by acid extract of anterior pituitary alone. We now report on the continuation of our investigations into the relation between the anterior pituitary and thyroid glands.

Effect of Hormones of Anterior Pituitary on Thyroid Gland in the Guinea-Pig.

In former investigations Loeb1,3 and Loeb and Kaplan2 have shown that feeding of tablets of anterior pituitary substance (Armour & Co.) prevents, in the guinea pig, compensatory hypertrophy which otherwise occurs in many cases after the greater part of the thyroid has been extirpated. H. A. McCordock4 through feeding of these tablets prevented the marked cell proliferation which occurs in the guinea pig after administration of potassium iodide. There are also prevented the slight changes in colloid and in the size of the acinus cells caused by iodine. These experiments proved that in Armour's Anterior Pituitary preparation there is present a substance which prevents growth processes (hypertrophy and hyperplasia) in the thyroid of the guinea pig.However, in larvae of amphibia, it has been shown that removal of the anterior pituitary may cause atrophic changes in the thyroid gland (B. M. Allen,5 P. E. Smith6) or, conversely, that injection of acid extracts of anterior pituitary may stimulate the thyroid gla...