Local action of exogenous growth hormone and insulin-like growth factor-I on dihydroxyvitamin D production in LLC-PK1 cells

Abstract

Previous in vivo studies have shown that growth hormone (GH) affects vitamin D and mineral metabolism. Insulin-like growth factor-I (IGF-I) was recently reported to be a regulator of renal 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ) production, suggesting that it mediates the effects of GH on vitamin D metabolism. However, there is no direct evidence to support this. The present study was designed to investigate the in vitro effects of GH and IGF-I on the renal production of 1,25- (OH) produced were determined after lipid extraction and HPLC purification. Production of 1,25-(OH) 2 D 3 and 24,25-(OH) 2 D 3 was increased after both IGF-I and GH preincubation in a dose-dependent manner. Significant increases were found after preincubation with 13 nmol/l IGF-I (1,25-(OH) 2 D 3 , 1.8-fold; 24,25-(OH) 2 D 3 , 1.5-fold) or 0.9 or 9 nmol/l GH (1,25-(OH) 2 D 3 , 1.3-fold and 1.5-fold; 24,25-(OH) 2 D 3 , 1.4-fold and 1.5-fold respectively). Furthermore, the effect of 9 nmol/l GH on 1,25-(OH) 2 D 3 and 24,25-(OH) 2 D 3 production was blocked in the presence of IGF-I receptor monoclonal antibody. These results confirm that IGF-I acts on renal tubules, resulting in induction of 1,25-(OH) 2 D 3 and 24,25-(OH) 2 D 3 production, and the findings suggest that GH stimulates 1,25-(OH) 2 D 3 and 24,25-(OH) 2 D 3 production by increasing local IGF-I production in the kidney.

IGF-I and GH stimulate Phex mRNA expression in lungs and bones and 1,25-dihydroxyvitamin D(3) production in hypophysectomized rats

“…kidney cells in vitro (51). Our findings indicate that the well-documented in vitro stimulation of vitamin D metabolism by IGF-I (52, 53) could be relevant in vivo.…”

Longitudinal changes in maternal serum 1,25-dihydroxyvitamin D and insulin like growth factor I levels in pregnant women who developed preeclampsia: comparison with normotensive pregnant women

“…Several studies have demostrated that IGF-I is a stimulatory factor of renal and placental 1,25-(OH) 2 D synthesis [1][2][3][4][5][6][7][8][9][10][11][12]. These observations prompted us to study longitudinal changes of 1,25-(OH) 2 D and IGF-I serum levels in pregnant women who remained normotensive and to determine whether alterations in circulating levels of these two hormones could be observed in women before they developed PE.…”

“…It has been reported that insulin-like growth factor I (IGF-I) stimulates renal 1,25-dihydroxyvitamin D (1,25-(OH) 2 D) production in nonpregnant human and rodents [1][2][3][4][5][6][7][8][9][10]. In addition, previous results from this laboratory showed a stimulatory effect of IGF-I on placental 1,25-(OH) 2 D synthesis [11,12], indicating that this growth factor could be a physiological regulator of Vitamin D metabolism during pregnancy.…”

Vitamin D increases circulating IGF1 in adults: potential implication for the treatment of GH deficiency

“…It has long been known that insulin-like growth factor 1 (IGF1) causes an increase in the circulating levels of 1,25-dihydroxyvitamin D (1,25(OH) 2 D), the hormonally active vitamin D metabolite, by stimulating the expression and activity of the 1a-hydoxylase that produces 1,25(OH) 2 D in the kidney (1,2). Indeed, plasma 1,25(OH) 2 D is significantly higher in active than controlled acromegaly, with a tendency to hypercalcemia, hyperphosphatemia, and hypercalciuria (3).…”