Modulatory effect of raloxifene and estrogen on the metabolic action of growth hormone in hypopituitary women.
BACKGROUND
The metabolic action of GH is attenuated by estrogens administered via the oral route. Selective estrogen receptor modulators lower IGF-I to a lesser degree than 17beta-estradiol in GH-deficient women, and their effect on fat and protein metabolism is unknown.


OBJECTIVE
The aim of the study was to compare the modulatory effects of 17beta-estradiol and raloxifene, a selective estrogen receptor modulator, on the metabolic action of GH.


METHODS
We conducted an open-label, two-group, randomized, two-period crossover study.


METHODS
Ten hypopituitary women received GH therapy alone (0.5 mg/d) and GH plus 17beta-estradiol (E(2); 2 mg/d). Eleven hypopituitary women received GH therapy alone and GH plus raloxifene (R; 60 mg/d). The treatment duration was 1 month, with a 4-wk washout period.


METHODS
IGF-I, IGFBP-3, resting energy expenditure, and fat oxidation were quantified by indirect calorimetry. We measured whole body leucine turnover from which leucine rate of appearance and leucine incorporation into protein were estimated.


RESULTS
GH significantly stimulated all outcome measures. During GH treatment, addition of R significantly reduced mean IGF-I but not IGFBP-3, whereas E(2) reduced both IGF-I and IGFBP-3 levels. Cotreatment with R but not E(2) significantly attenuated the stimulatory effects of GH on fat oxidation. There was a strong trend (P = 0.08) toward a greater reduction in leucine incorporation into protein after R compared to E(2) cotreatment.


CONCLUSIONS
The modulatory effects of E(2) and R at therapeutic doses on GH action are different. R during GH therapy exerts a greater inhibitory effect on lipid oxidation and protein anabolism compared to E(2).
Birzniece
Vita
V
Garvan Institute of Medical Research and Department of Endocrinology, St. Vincent's Hospital, Darlinghurst, NSW 2010, Australia.
Meinhardt
Udo
U
Gibney
James
J
Johannsson
Gudmundur
G
Baxter
Robert C
RC
Seibel
Markus J
MJ
Ho
Ken K Y
KK
D000328:Adult; D002153:Calorimetry, Indirect; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008875:Middle Aged; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use
D018972:Insulin-Like Growth Factor Binding Protein 3; D020845:Selective Estrogen Receptor Modulators; D019382:Human Growth Hormone; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007930:Leucine