Effects of gonadal steroid withdrawal on serum phosphate and FGF-23 levels in men.
BACKGROUND
Fibroblast growth factor (FGF-23) is a novel phosphaturic factor. Current data suggest that serum phosphate, dietary phosphate and 1,25 dihydroxyvitamin D regulate circulating FGF-23 levels in vivo. We examined if hypogonadism-induced increases in serum phosphate are associated with increases in circulating FGF-23 in healthy men in the absence of dietary manipulation.


METHODS
25 healthy men were administered goserelin acetate (GnRH analog) 3.6 mg subcutaneously every 4 weeks for 12 weeks to induce acute testosterone and estrogen deficiency. Subjects consumed an ad libitum diet. Morning fasting blood and urine samples were collected to measure serum phosphate, serum intact FGF-23, PTH, and the maximum tubular reabsorption of phosphate (T(m)P/GFR) at baseline, weeks 4 and 12. The changes in serum FGF-23 and phosphate at weeks 4 and 12 were compared to baseline using paired t-tests.


RESULTS
Goserelin therapy decreased mean serum testosterone levels from 543+/-160 ng/dL to 33+/-15 ng/dL at week 4 (p<0.001), and to 20+/-10 ng/dL at week 12 (p<0.001). Serum phosphate increased significantly from 3.4+/-0.6 mg/dL to 3.9+/-0.4 mg/dL at week 4 (p=0.002), and to 4.3+/-0.4 mg/dL at week 12 (p<0.001). T(m)P/GFR increased significantly from 3.2+/-0.6 mg/dL to 3.6+/-0.5 mg/dL at week 4 (p<0.004), and to 4.1+/-0.6 mg/dL at week 12 (p<0.001). FGF-23 levels, however, did not change during the 12-week study.


CONCLUSIONS
Gonadal steroid deprivation increased serum phosphate levels in men but did not affect serum FGF-23 concentrations. The absence of any change in circulating FGF-23 suggests that supraphysiologic levels of serum phosphate may be required to stimulate circulating FGF-23 or that FGF-23 production is primarily sensitive to changes in dietary phosphate or 1,25 dihydroxyvitamin D within this physiologic serum phosphate range.
Burnett-Bowie
Sherri-Ann M
SM
Endocrine Unit, Thier 1051, Massachusetts General Hospital, 50 Blossom Street, Boston, MA 02114, USA. sburnett-bowie@partners.org
Mendoza
Natalia
N
Leder
Benjamin Z
BZ
D000328:Adult; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D024042:Collagen Type I / Q000097:blood; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D017273:Goserelin / Q000494:pharmacology*; D006801:Humans; D007006:Hypogonadism / Q000097:blood* / Q000139:chemically induced; D008297:Male; D015999:Multivariate Analysis; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000097:blood; D010710:Phosphates / Q000097:blood*; D013739:Testosterone / Q000097:blood / Q000172:deficiency
D024042:Collagen Type I; C000717427:FGF23 protein, human; C470125:PTH protein, human; D010281:Parathyroid Hormone; D010455:Peptides; D010710:Phosphates; C052929:collagen type I trimeric cross-linked peptide; D017273:Goserelin; D013739:Testosterone; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol; D002118:Calcium