CALCIUM MODULATION OF ADRENOCORTICOTROPIN LEVELS IN WOMEN - A CLINICAL RESEARCH-CENTER STUDY

In vitro calcium modulation of anterior pituitary hormone secretion ha s been well described. In addition, several investigations performed i n human subjects have documented modulation of the circulating levels of pituitary hormones by supraphysiological calcium concentrations. Re cent data from our laboratory document the existence of an extracellul ar calcium-sensing receptor that is thought to mediate the effects of variations in extracellular calcium on the secretion of PTH and calcit onin. We have also demonstrated the presence of this receptor in pitui tary-derived, ACTH-secreting AtT-20 cells as well as in the anterior p ituitary of rats and mice. In the present study we investigated the ef fect on anterior pituitary hormone levels of variations in serum calci um within the physiological range. We serially measured serum levels o f ionized calcium (Ca-i), ACTH, cortisol, TSH, and PRL during 90-min i v infusions (on separate days) of calcium, citrate, and dextrose in 10 healthy women with a mean age of 55 +/- 5 yr. During the calcium infu sion, the serum Ca, level increased significantly from 4.32 +/- 0.10 m g/dL at baseline to 4.86 +/- 0.08 mg/dL at completion (P = 0.002), and this change was accompanied by a significant increment in the serum A CTH level from 9.87 +/- 1.32 to 16.31 +/- 2.84 pg/mL (P = 0.0008). The re was no change in the serum ACTH level during the citrate infusion d espite significant decrements in serum Ca-i, nor were there changes in either Ca-i or ACTH during the dextrose infusion. Finally, changes in Ca-i did not alter TSH or PRL levels. In summary, our dynamic studies are the first to demonstrate an increase in baseline serum ACTH level s in response to physiological increments in Ca-i (i.e. increments wit hin the normal range). This effect was specific for increments and not decrements in serum Ca-i and was selective for ACTH, as TSH and PRL l evels did not change with any of the infusions.