Eric Lifrak

Aging and the Human Zona Reticularis

Adrenal androgen levels and excretion increase during adrenarche and puberty. During this time the width of the adrenal zona reticularis has been reported to increase, and this fact is quoted as evidence for the common assumption that the major source of adrenal androgens is the zona reticularis. During human aging there is a marked decrease in adrenal androgen levels and excretion. In the present study, the width of the zona reticularis was studied single blind in multiple sections of the adrenals of 42 victims of sudden death 4 months to 93 years of age to discern a possible correlation between zona reticularis width and the declining adrenal androgen levels and excretion typical of aging. However, no correlation was found, which suggests that direct measurements of adrenal steroid secretion by the individual adrenal zones are necessary for the study of adrenal zonation.

16,16-Dimethyl prostaglandin E2 reduces bile acid-mediated intestinal vascular injury in rats

To examine the effects of prostaglandin on bile acid-mediated intestinal vascular injury, male rats were given 50 mg/kg of fluorescein isothiocyanate (FITC)-stained dextran 70 or 25 mg/kg of Evans Blue intravenously. Before intestinal injury with 45-minute perfusion of 5 mmol/L chenodeoxycholic acid, rats received 16,16-dimethyl prostaglandin E2 (5 micrograms/kg intravenously or 0.5 micrograms/mL or in the perfusate for 15 minutes or vehicle). FITC-dextran clearance from the blood to the intestinal lumen and tissue Evans Blue content were used as measures of intestinal vascular injury. Morphological mucosal injury was assessed by transmission electron microscopy and quantitative histological analysis. Chenodeoxycholic acid perfusion caused villous denudation and shortening of and ultrastructural damage to villous venules. Functional vascular injury was evidenced by a 10-fold increase in the rate of FITC-dextran blood-to-lumen clearance and a 3-4-fold increase in tissue Evans Blue content. Pretreatment with either intravenous or intraluminal 16,16-dimethyl prostaglandin E2 reduced FITC-dextran clearance by 70%-80% and tissue Evans Blue content by 50%. However, only luminal prostaglandin reduced superficial mucosal morphological injury, possibly because of differences in the local concentrations of 16,16-dimethyl prostaglandin E2 or chenodeoxycholic acid or because of superficial mucosal protection and injury being, at least in part, independent of mucosal microvascular injury and protection.

Angiotensin II potentiates ACTH-stimulated adrenal androgen secretion

Several lines of evidence in animal and human studies, including measurements of elevated adrenal androgens in salt wasting syndromes suggest that adrenal androgen levels may in part be regulated by angiotensin II. This possibility was tested directly by measurement of cortisol and dehydroepiandrosterone (DHA) in canine adrenal cell suspensions after addition of angiotensin II and ACTH, separately and together. Minimal cortisol and no DHA stimulation was obtained using 4 x 10(-10) to 4 x 10(-5) M concentrations of angiotensin II alone. However, increased cortisol and DHA secretion were observed beginning at 4 x 10(-10) M concentrations of angiotensin II when it was combined with 10(-13) MACTH. These are physiological concentrations of both stimuli and may explain the increased adrenal androgens seen in some pathological situations characterized by elevated PRA.

Chronic omeprazole treatment increases duodenal susceptibility to ethanol injury in rats

To test whether omeprazole would increase the susceptibility of the duodenum to damage, 200 to 250-g male Sprague-Dawley rats were given 10 mg/kg of omeprazole (Losec) by gavage every morning for 29 days. Control rats were given gavage buffer alone. After fasting overnight, half the rats received 10 mg/kg indomethacin intraperitoneally; then all rats were given 2 ml of 50% ethanol by gavage. Three hours later the rats were killed and the stomach and duodenum removed and histologic injury to the duodenal mucosal was quantitated. In omeprazole pretreated rats, gavage with ethanol resulted in a significant twofold worsening of duodenal injury. Pretreatment with indomethacin to decrease endogenous prostaglandin production resulted in more severe ethanol-induced duodenal injury in both groups; however, there were no longer statistically significant differences between the omeprazole and control groups. Measurement of duodenal mucosal synthesis of prostaglandin E2 showed no difference between the omeprazole and control groups. Thus chronic administration of omeprazole appears to increase the susceptibility of the duodenal mucosa to ethanol injury in rats. The mechanism of this effect is as yet unknown but does not appear to be prostaglandin-mediated.