Effects of short‐term insulin‐like growth factor‐I or growth hormone treatment on bone turnover, renal phosphate reabsorption and 1,25 dihydroxyvitamin D₃ production in healthy man

Abstract

Objectives. To find out whether insulin‐like growth factor‐I (IGF‐I) mimics the stimulatory effects of growth hormone (GH) on bone turnover and renal tubular phosphate reabsorption. Design. Randomized, crossover study. Setting. University Hospital, Zürich, Switzerland. Subjects. Seven young healthy male subjects. Interventions. Each subject was studied three times at 2‐week intervals, treated with saline 0.9% (S), IGF‐I [8 μg kg−1 h−1] by a continuous subcutaneous infusion and finally with GH (6 U. twice daily s.c.) for 5 days. Main outcome measures. 36 h after the start of treatment, IGF‐I, biochemical markers of bone turnover, calcium, calcium regulating hormones, kidney function and phosphate reabsorption were measured in serum and in 2 h urine in fasting state. Results. Serum levels of IGF‐I were 26.8±7.3 (S), 119.4±11.4 (IGF‐I) (P<0.02) and 58.4±12.9 nmol L−1 (GH) (P<0.02), respectively. Serum osteocalcin and carboxyterminal propeptide of type I collagen (PICP) as well as the urinary deoxypyridinoline/creatinine and the calcium/creatinine ratios were all significantly higher after IGF‐I (P<0.02) or GH (P<0.02) than after saline treatment. PTH levels did not change in response to treatment. Total albumin‐corrected calcium increased only after GH treatment (P<0.05). The free calcitriol index rose from 2.2.±0.5×10−5 (S) to 2.81±0.25×10−5 (IGF‐I) (P<0.03) and 2.45±0.25×10−5 (GH), respectively. Serum phosphate and maximal tubular reabsorption divided by glomerular filtration rate (TmP/GFR) were significantly raised by GH (P<0.03) but not by IGF‐I as compared to saline 0.9%. Conclusions. (i) Similar to GH, IGF‐I rapidly activates bone turnover. (ii) IGF‐I does not mimic the effect of GH on renal phosphate reabsorption in spite of comparable effects on renal blood flow and glomerular filtration rate. (iii) IGF‐I increases free calcitriol index in face of unchanged serum levels of calcium, phosphate and PTH, consistent with a direct stimulatory effect on 25‐OHD‐1a‐hydroxylase.

Identification of Bioactive Molecules by Adipogenesis Profiling of Organic Compounds

“…Deficiency in IGF1, a prominent member of IGFs, is suggested to be a cause of decrease in bone density with aging (20,21), and administration of IGF1 prevents the decrease of bone density in osteoporosis patients in part by stimulating osteogenesis (22)(23)(24). The high homology between IGF1 and insulin suggested that the osteogenesis-enhancing activity of IGF1 may be mimicked by the chemicals that potentiated the insulin-induced adipogenesis.…”

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).…”

Vitamin D across growth hormone (GH) disorders: From GH deficiency to GH excess

“…Similar stimulatory effects were obtained when GH was administered for a short-time. Brixen et al showed a significant increase in total vitamin D in 20 normal male volunteers after just 7 days of treatment with a pharmacological dosage of GH [13], and GH infusions in 7 normal healthy male volunteers increased 1,25(OH)2-D3 levels within 36 h [14].…”

“…Therefore, one potential mechanism by which GH stimulates increases in bone mass is via increases in IGF-I and consequently in [17]. Indeed, it is widely demonstrated that IGF-I causes an increase in the circulating levels of 1,25(OH)2-D3 by directly stimulating expression and activity of the 1α-hydoxylase that produces 1,25(OH)2-D3 in the kidney [14,18].…”