GROWTH-HORMONE AND PARATHYROID-HORMONE STIMULATE INTESTINAL CALCIUM-ABSORPTION IN AGED FEMALE RATS

Aged (16-month-old) female rats (n = 8/treatment) were injected for 12 days with GH (100 mug/100 g-day), PTH (8 mug/100 g.day), GH plus PTH, or vehicle (V) in an experiment designed to determine the effects of these hormones on intestinal mineral absorption in senescent rats. PTH and GH increased fractional net calcium absorption to a similar extent (PTH, 1.6-fold; GH, 1.4-fold) even though PTH increased serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] 3.7-fold, and GH had no significant effect. GH plus PTH caused no further increase in serum 1,25-(OH)2D3 above that caused by PTH alone, but resulted in an additive effect on net calcium absorption (2.3-fold increase). PTH and GH also had statistically independent effects on phosphate absorption; magnesium absorption was elevated only by PTH. Duodenal calbindin-D9k levels were increased by GH (from 3.79 +/- 0.72 to 6.98 +/-0.73 mug/mg protein) and PTH (from 3.23 +/- 0.46 to 7.55 +/- 0,75 mug/mg protein); PTH plus GH treatment resulted in an additive effect on calbindin-D9k levels. Additional in vitro transport studies in the human intestinal cell line Caco-2 showed that 72 h of pretreatment with the local mediator of GH action, insulin-like growth factor-I (at 10 and 100 ng/ml), stimulated transcellular calcium transport (22% and 44%, respectively) regardless of concomitant 1 nM 1,25-(OH)2D3 pretreatment (80% increase). Our findings suggest a 1,25-(OH)2D3-mediated mechanism for PTH-induced changes in calcium and phosphorus absorption. In contrast, the effects of GH in the senescent rat are independent of changes in circulating 1,25-(OH)2D3, and our data suggest that these effects may be mediated by insulin-like growth factor-I.