The interrelation between thyroid, bypophysis and adrenals under conditions of stress, with especial reference to pituitary cytology
McNary, William Francis
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The purpose of this investigation was to study the interrelation, in the rat, between the adrenal gland and the hypophysis, and between the thyroid gland and the hypophysis with respect to changes in the cytological structure of the anterior lobe as a result of the subjecting the animal to stress. A survey of the literature revealed many contradictory reports concerning the cytological changes produced in the anterior hypothalamus by subjecting the animal to a stimulus to which the animal is not adapted. Since Selye (Canad. M.A.J., 34: 706-707 1936) first proposed his hypothesis that the adrenal cortex participated in the reaction to stressful conditions. The interrelation of the hypophosis and adrenal glands has been the subject of many investigations. These investigations have elevated the pituitary-adrenal axis to a position of central importance in the "homeostatic" or defensive reactions of the animal when it is placed in a noxious environment. The function of the hypophysis in the regulation of these defense reactions has been shown by many workers. Removal of the hypophysis results in atrophy of the adrenal gland and reduces the ability of the animal to resist stressful conditions. The interrelation between the thyroid gland and the hypophysis under similar conditions of stress has been studied less extensively. The results reported in this investigation demonstrate that the participation of the thyroid gland, as well as the adrenal medulla, in these reactions to stress is also of importance. This was shown by the cytological changes that occurred in the anterior lobe of the hypophysis of the stressed animals. In the present investigation, the cells of the anterior hypopysis were evaluated by means of 3 principal methods: 1. Cytological studies in which the major differential staining methods were compared. 2. Differential cell counts. 3. Absolute cell counts per unit area. The forms of stress used were exposure to a cold environment and the subcutaneous injection of formalin. These forms of stress were chosen because the animal can sustain these stimuli for prolonged periods of time; they produce little direct tissue damage; they permit the comparison of the results of this investigation with those of others. The thyroid and the adrenal glands were examined and the structural changes observed in these organs were correlated with the cytological changes observed in the anterior hypophysis. The Cytology of the Anterior Hypophysis after Formalin Stress This experiment was designed after Brokaw er al (Texas Rep. Biol. and Med., 8: 312 - 319 1950). Cytologically the anterior hypophysis of the formalin-stressed animals demonstrated no differences from the normal. Differential cell counts, however, revealed a statistically significant increase in the percentage of scidophil cells (P=0.01) in the formalin-stressed animals. Formalin stress in unilaterally adrenalectomized animals also produced a significant increase in the percentage of scidophils (P=0.02), but this increase was less than that produced in the intact animal. Differential leucocyte counts and total leucocyte counts revealed a statistically significant increase of the total number of leucocytes and of the percentage of neutrophils in both the intact and the unilaterally adrenalectomized animals. A statistically significant decrease in the percentage of lymphocytes was found also after formalin stress. Short-Term Cold Exposure The animals of this group were exposure to the cold environment for periods of 1 to 10 hours. Cytologically the major differential staining methods and the differential cell counts failed to reveal any difference between the cells of the anterior hypophysis of the cold-exposed animals and the normal ontrol animals. Sections stained with Rennels' modification of Baker's acid hematein method (Rennels, E.G., personal communication 1952), however, revealed a change in the phospholipid containing cells (acidophile) after 1 hour of cold exposure. After 4 hours of cold, these phospholipid containing cells had increased in number per unit area to a significant level (P=0.01). This increase reached a meximum point after 8 hours of cold. Absolute eosinophil counts showed a statistically significant increase in the number of eosinophils after 2 and after 3 hours of cold, but not after longer periods of exposure. Long Term Cold Exposure The animals in this group were exposed to the cold environment for periods of 1 to 61 days. Cytologically the basophils demonstrated degranulation and vacuolation after 10 days of exposure to the cold environment. The beta cells of Halmi (Endocrinology, 47: 289 -2 99 1950) were degranlated and the detla cells were significantly increased in number (P=0.01). After approximately 30 days of cold exposure, the beta cells were regranulated and were significantly increased in number (P=0.02). The delta cells after 30 days retuned to normal levels. After 51 to 61 days of cold exposure the differential cell counts were not significantly different from the normal. Sections stained with the acid hematein method demonstrated that the increase in number per unit area of the phospholipid containing cells produced by short-term cold exposure was maintained at statistically significant levels throughout the 61 day period. Sections of the thyroid gland demonstrated a progressive increase in the height of the epithelium of the follicle after 2 to 61 days of cold exposure. The maximum increase at 61 days was 63.6 percent. Uncer these conditions of stress the adrenal glands remained essentially normal in both weight and in histological appearance. Studies on the Phospholipid Containing Cells of the Anterior Hypophysis In 1952 Finerty et al (Anat. Rec., 114: 115 - 126) suggested that changes in the phospholipid containing cells of the anterior lobe of the hypophysis were associated with an increased secretion of the adrenocorticotrpphic hormone. Since an increase in the number of phospholipid cells per unit area was demonstrated after cold exposure, experiments were designed to determine the relation of adrenal function to this change in the anterior hypophysis. These experiments and their results were follows: A. Thyroidectomy and Thyroidectomy with Cold-stress. The changes observed in the anterior lobe of the phypophysis after throidectomy confirmed Rennels' observations (Anar. Rec., 115: 659 - 672). Thyroidectomy causes complete disappearance of the phospholipid cells within the gland. Cold exposure failed to cause a reappearance of the phospholipid cells in the thyroidectomized animal. B. Adrenalectomy and Adrenalectomy with Cold-stress. Adrenalectomy failed to produce any change in the number of phospholipid cells such as occurs in normal animals subjected to cold. Sham adrenalectomized animals demonstrated this increase. C. The Subcutaneous Injection of Cortisone in Both Intact and Adrenalectomized Animals. The subcutaneous injection of cortisone (approx. 7.5mg/100g body weight) produced an increase in the number of phospholipid cells per unit area in the intact animal, but failed to cause any change in the adrenalectomized animal. D. The Subcutaneous Injection of Epinephrine in Both Intact and Adrenalectomized animals. The subcutaneous injection of epinephrine (approx. 0.02mg/100g body weight) resulted in an increase in the number of phospholipid cells in both adrenalectomized and intact animals. E. Adrenal Demedullation and Adrenal Demedullation with Cold-stress. Adrenal demedullation produced an increase in the number of phospholipid cells per unit area 30 days after the operation. Exposure of the demedullated animal to cold stress resulted in a statistically significant decrease (P=0.01) in the number of phospholipid cells when compared to the non-stressed demedullated animal. The validity of the results obtained by the field-count method was tested by determining the coefficient of correlation between the total number of all cells per unit area. This correlation was not significant. Therefore, the increase in the number of phospholipid containing cells in the anterior lobe of the hypophosis is the result of an increase in the total number of cells containing phospholipid material and not the result of an increase in the total number of cells per unit area. The results of this investigation are discussed with reference to the participation of the thyroid and the adrenal medulla in the reaction to stress. The relations between the anterior hypophysis and the adrenal glands and the anterior hypophysis and the thyroid gland are also considered.
Thesis (Ph.D.)--Boston University