Activation of renal 1,25-dihydroxyvitamin D3 synthesis by phosphate deprivation: evidence for a role for growth hormone.
In vitro 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] production in kidney slices from normal intact rats averaged 16 +/- 4 pmol/g . h and was increased about 8-fold by phosphate deprivation and 5-fold by calcium deprivation to levels averaging 128 +/- 12 and 84 +/- 19 pmol/g x h, respectively. Hypophysectomy in phosphate-deprived rats completely abolished any increase in 1 alpha-hydroxylase activity, while calcium deprivation in hypophysectomized (hypox) rats resulted in a 4-fold increase in 1 alpha-hydroxylase activity. Replacement of hypox rats fed a low phosphorus diet with pituitary extracts resulted in a 4-fold stimulation of 1 alpha-hydroxylase activity in response to the hypophosphatemic stimulus. However, replacement of hypox rats fed a normal phosphorus diet with pituitary extract stimulated 1 alpha-hydroxylase activity only 2-fold. Replacement of hypox rats fed a low phosphorus diet with GH resulted in a 3.5-fold elevation in plasma 1,25-(OH)2D3 levels, while no such elevation in plasma 1,25-(OH)2D3 levels was observed in similarly treated animals replaced with PRL, ACTH, TSH, or T3. Replacement of hypox rats eating a normal diet with GH resulted in no significant change in plasma 1,25-(OH)2D3 levels. These results suggest that GH is required for maintenance of elevated plasma 1,25-(OH)2D3 levels during dietary phosphate deprivation and that this effect is mediated by increased renal 1,25-(OH)2D3 synthesis.
D000818:Animals; D002117:Calcitriol / Q000096:biosynthesis* / Q000097:blood; D002118:Calcium / Q000172:deficiency; D013006:Growth Hormone / Q000097:blood / Q000494:pharmacology*; D007016:Hypophysectomy; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010758:Phosphorus / Q000172:deficiency*; D010902:Pituitary Gland / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013250:Steroid Hydroxylases / Q000378:metabolism; D014020:Tissue Extracts / Q000494:pharmacology
D014020:Tissue Extracts; D010758:Phosphorus; D013006:Growth Hormone; D013250:Steroid Hydroxylases; D002117:Calcitriol; D002118:Calcium