Upsala J Med Sci 79: 90-93, 1974 Parathyroid Hormone and Gastric Mucosal Surface Ultrastructure B. FRENNING, H. JOHANSSON and P. G . OHRN From the Departments of Medicine, Surgery and Clinical Research II, University Hospital, U p p s a l a , Sweden ABSTRACT Examination in the SEM of gastric mucosa from rats given parathyroid hormone appeared to reveal an in- creased incidence of unspecific damage on the luminal surfaces of the gastric mucosal surface epithelial cells. The finding may he related to the suggested ulcer- ogenic effect of the hormone. INTRODUCTION A relationship between hyperfunction parathyroid glands and gastrointestinal of the disturb- ances and gastric ulcers is often suggested both in man and in experimental animals (8, 9, 10). There appears t o be no difference between man and the rat in this respect, though the basal gastric secretion is increased in at least some of the patients with hyperparathyroidism (3, 4, 15, cf. 2 ) , whereas it is decreased by treatment with parathyroid hormone (PTH) i n the rat (1, 13). In a previous investigation (13) an increased serum calcium level, a reduced secretion rate and reduced acidity in the basal gastric secretion were noted in rats treated with PTH for 14 days. This result might have been due to an inhibitory effect of this hormone on the gastric secretion, but an increased permeability of the gastric mucosa caus- ing an increased back-diffusion of hydrogen ions would have given the same result (5, 1 1 , 12, 14). To examine the effects of PTH further gastric mucosa from rats treated with the hormone and from untreated controls were examined in the scanning electron microscope (SEM). A prelimin- ary report of the findings is given in this paper. MATERIAL AND METHODS The experiments were performed on male albino rats weighing about 200 g. Five rats were given parathyroid hormone (Para-Thor-Mone, Ely, Lilly) S.C. twice a day for 14 days in a dose of 40 USP units/100 g body weight/ day. Three control animals were given physiological saline S.C. twice a day. Under general anaesthesia 2.5 55 glutaraldehyde in phosphate buffer was instilled intragastrically via a rub- ber tube. Five minutes later the stomachs were removed and specimens from the glandular portions were taken in duplicate. After the initial glutaraldehyde fixation post- fixation was performed in 1% osmium tetroxide. The specimens were dehydrated in a graded acetone series. After drying they were mounted on brass stubs with an adhesive and electrical continuity was ensured by paint- ing with colloidal silver. They were covered by cold- palladium in a vacuum-evaporator (Jeol, J E E 48) and exa- mined in a Jeol SEM (JSM-U3). For details regarding the preparation procedure see (5) or (7). RESULTS The appearance of gastric mucosa from a rat given PTH is shown in Fig. 1 . The surfaces of quite a few cells were irregular and appeared unspecific- ally damaged. No changes were observed along the intercellular borders. Fig. 2 shows a similar area from an untreated control animal. In Figs. 3 and 4 damaged and normal surface epithelial cells are seen at a higher magnification. In both these micrographs some microvilli are observed. Most of these structures appeared t o be covered by mucus, however. It must be pointed out that signs of unspecific damage similar to those shown in Figs, 1 and 3 were occasionally seen on the Upsala J M e d Sci 79 Parathyroid hormone and gastric mucosa 91 F i g . I . Micrograph of gastric mucosa from a rat treated with parathyroid hormone for 14 days. The openings of control specimens. The changes observed on specimens from PTH treated rats seemed to be more pronounced, however, and the damaged cells more numerous. DISCUSSION The type of damage noted on gastric mucosa from PTH treated rats was not observed on cat gastric mucosa exposed to aspirin, acetic acid or hyperos- motic sodium chloride solutions (5, 6, 7). Sub- sequent to exposure of gastric mucosa to these weak acids (7) or to large osmolaiity variations (6) the appearance of the gastric mucosal surface epithelium was also changed from normal. In these cases the changes were of different natures, how- ever. As to the origin of the observed changes it is only possible t o speculate. One suggestion is that PTH treatment may make the cell surfaces more susceptible for peptic digestion. The changes appear to be sufficient to explain the decreased gastric secretion observed after PTH treatment of ~ three crypts are seen. Some cells appear unspecifically damaged. ( ~ 3 0 0 0 . ) rats as an effect of an increased back-diffusion of hydrogen ions (5, 11, 12, 14). They may be related to the suggested ulcerogenic effect of the hor- mone. ACKNOWLEDGEMENTS We are very grateful to Mrs Margareta Einarsson and Mr B. Wieselblad for technical assistance. The work was supported by the Swedish Medical Research Council, project No. 17X-3498. REFERENCES Arnthorsson, G . , O h m , P. G . & Segerstrom, A.: Gastric secretion in relation t o parathyroid dysfunc- tion in rats with chronic gastric fistulae. Upsala J Med Sci 78:55-59, 1973. Barreras, R. F . : Calcium and gastric secretion. Gastroenterology64: 1168-1 184, 1973. Barreras, R . F. & Donaldson, R . M., Jr: Role of calcium in gastric hypersecretion, parathyroid ade- noma and peptic ulcer. N Engl J Med 276: 1122- 1124, 1967. Christiansen, J . & Aagaard, P.: Parathyroid adenoma and gastric acid secretion. Scand J Gastroent 7:445- 449, 1972. Upsala J Med Sci 79 92 B . Frenning et al. F i g . 2 . Micrograph of gastric mucosa from a control animal. Here also the openings of three crypts are ob- served. ( ~ 3 0 0 0 . ) F i g . 3. Damaged surface epithelial cells on gastric mucosa from a PTH treated rat. Along the intercellular borders some microvilli are seen. ( ~ 6 0 0 0 . ) Upsala J Med S c i 79 Parathyroid hormone and gastric mucosa 93 F i g . 4. Normal surface epithelial cells. Some microvilli can be observed in this micrograph also. Most of these 5. 6 7. 8. 9. 10. 11. 12. 13. Frenning, B.: Ion transport and surface ultrastructure in the non-secreting stomach. Upsala J Med Sci, Suppl. 13, 1972. - The effects of large osmolality variations on the gastric mucosal surface ultrastructure. Scand J Gastroent 8: 185-192, 1973. Frenning, B. & Obrink, K. J.: The effects of acetic and acetylsalicylic acids on the appearance of the gastric mucosal surface epithelium in the scanning electron microscope. Scand J Gastroent 6: 605-612, 1971. Hellstrom, J.: Hyperparathyroidism and gastroduo- denal ulcer. Acta Chir Scand 116:207-221, 1959. Johansson, H . , Thoren, L. &Werner, I . : Hyperpara- thyroidism. Clinical experiences from 208 cases. Upsal J Med Sci 77:41-46, 1972. Kelly, T. R. : Relationship of hyperparathyroidism to peptic ulcer. Arch Surg (Chicago) 101: 193-199, 1970. Nordgren, B.: The rate of secretion and electrolyte content of normal gastric juice. Acta Physiol Scand, Suppl. 202, 1963. Obrink, K. J.: Studies on the kinetics of the parietal secretion of the stomach. Acta Physiol Scand, Suppl. 51, 1948. Ohm, P. G., Frenning, B., Hessman, Y . , Johansson, H . & Segerstrom, A,: Influence of parathyroid hor- mone and vitamin D on basal gastric secretion in rats. Scand J Gastroent (in press). structures appear to be covered by mucus, however. ( x6000.) 14. Teorell, T.: Electrolyte diffusion in relation to the acidity regulation of the gastric juice. Gastroentero- logy 9: 425-443, 1947. 15. Ward, J. T . , Adesola, A. 0. & Welbourn, R. B.: The parathyroids, calcium and gastric secretion in man and the dog. Gut 5: 173-183, 1964. Received October 28, 1973 Address for reprints: Bertil Frenning, M.D. Department of Medicine University Hospital S-750 14 Uppsala Sweden Upsala J Med Sci 79