Inhibitory action on GHRH-induced GH secretion of chronic tamoxifen treatment in breast cancer.
OBJECTIVE
Previous in vitro and in vivo studies on animal models have demonstrated that tamoxifen (TAM) inhibits GH secretion. Studies in humans are conflicting. The aim of this study was to evaluate the effect of chronic TAM treatment on GH secretory dynamics in the presence of negligible endogenous oestrogens, in postmenopausal women with breast cancer.


METHODS
Ten female patients were studied over a 6-12-month period after surgical therapy, before medical therapy, and during chronic treatment with TAM (20 mg/day p.o.).


METHODS
In all subjects we performed a standard GHRH-test (50 mg i.v. as a bolus) and compared the single time points, the peak response and the areas under the curves (AUC), before and during treatment. In basal samples, we evaluated the circulating levels of IGF-1, IGF-BP3 and their ratio, SHBG, FSH, LH, Oestradiol (E2) and PRL. GH was assayed by Immunoradiometric assay (IRMA). Insulin-like growth factor type I (IGF-I), Insulin-like growth factor-binding protein-3 (IGF-BP3), FSH, LH and PRL were measured by Radioimmunoassay (RIA). SHBG was measured by a noncompetitive liquid phase immunoradiometric assay, while E2 was measured directly in plasma by a liquid phase technique.


RESULTS
TAM chronic treatment significantly reduced GH response to GHRH at single time point evaluations, GH peak response (mean decrease: 59.8 +/- 7.3%) and GH-AUC (mean decrease 53.8 +/- 8.9%). TAM also significantly reduced plasma IGF-1 levels. No significant variations were found in IGF-BP3 levels or in the IGF-1/IGF-BP3 ratio. A significant inverse correlation between SHBG and IGF-1 circulating levels was noticed during TAM treatment.


CONCLUSIONS
Our data show that long-term tamoxifen treatment blocks the response of GH to exogenous GHRH and reduces IGF-1 levels, possibly by a central mechanism other than the demonstrated peripheral action. The results of this study, keeping in mind the demonstrated mitogenic role of IGF-1 in cancer proliferation, can contribute to clarify the mechanism by which TAM exerts its antiproliferative effect.
De Marinis
L
L
Institute of Endocrinology, Catholic University School of Medicine, Rome, Italy. laurademarinis@yahoo.it
Mancini
A
A
Izzi
D
D
Bianchi
A
A
Giampietro
A
A
Fusco
A
A
Liberale
I
I
Rossi
S
S
Valle
D
D
D000368:Aged; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D003864:Depression, Chemical; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D011388:Prolactin / Q000097:blood; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*
D018972:Insulin-Like Growth Factor Binding Protein 3; D020845:Selective Estrogen Receptor Modulators; D012738:Sex Hormone-Binding Globulin; D013629:Tamoxifen; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone