Alterations in secretion and fine structure of histamine stimulated stomach mucosa following administration of oestrogens

ABSTRACT

The observation that benign peptic ulceration is less common in females during the reproductive period and the suggestion that oestrogens have an inhibiting effect upon the activity of carbonic anhydrase led us to investigate volumetric and ionic (H+, K+, NA+, C1-.) changes in gastric secretion and also the fine structural changes in gastric oxyntic cells following administration of oestrogens. Fifteen male dogs after 24 hour fasting were anaesthetised with ketalamine hydrochloride and then subjected to a constant i.v. infusion of histamine phosphate, (approx. 14ug/Kg/hour). Twelve dogs underwent truncal vagotomy and ligation at the distal oesophagus. Gastric secretions were collected at 20 minute intervals via a tube introduced into the most dependant part of the stomach through a duodenotomy. The pylorus was ligated around the tube. Approximately 3 hours later, when three consecutive specimens were similar in volume, 4mgm/Kg Premarin (Eguine conjugated oestrogens) was injected i.v. into ten dogs. Further specimens were collected for three hours. Gastric mucosal biopsies were taken from three histamine stimulated dogs before and after injection of Premarin 4mgm/Kg. and were prepared for electron microscopy. The mean hourly volumes of secretion diminished at one, two and three hours after Premarin (ANOVA F 4.5; d.f. 333; p< 0.05) with an inhibition of 65.3 percent of the mean pre-Premarin value observed at the third hour. There was a significant rise in the mean pH one hour after Premarin in P<0.05, however, after this there was no significant variation. There was an apparent rise in the mean sodium concentration in the first two hours with a statistically significant rise at three hours after Premarin p<0.05. No significant changes were observed in the mean Potassium or Chloride concentration. The comparison of fine structure of 40 oxyntic cells, 20 before and 20 after Premarin injection, showed an apparent reduction in numbers of canaliculi, with lengthening of the canalicular microvilli. Except for the absence of demonstrable effects on Potassium and on cytoplasmic micro-vesicles these results are comparable with reported findings after inhibition of carbonic anhydrase by acetazolamide (AU)