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Inhibitory action on GHRH‐induced GH secretion of chronic tamoxifen treatment in breast cancer
Author(s) -
De Marinis,
Mancini Mancini,
Izzi,
Bianchi,
Antonella Giampietro,
Giuseppe Fusco,
Liberale,
Laura Lucia Rossi,
Valle
Publication year - 2000
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.2000.00991.x
Subject(s) - endocrinology , medicine , immunoradiometric assay , tamoxifen , radioimmunoassay , breast cancer , 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. PATIENTS 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.). MEASUREMENTS 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.