ESPE Abstracts (2021) 94 P2-77

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The First Affiliated Hospital of Sun Yat Sen University, GUANGZHOU, China


Background: Tamoxifen is a selective estrogen receptor modulator,administrated in girls with precocious puberty such as McCune-Albright syndrome.

Objective: To explore the effect of tamoxifen on the linear growth of precocious pubertal female rats.

Method: At 16-22 day of age, 16 precocious pubertal female rats(induced by 300 μg danazol s.c. at 5-day old), were randomized blocks (brood) to 2 groups(n = 8). Group TAM received once weekly 20mg/kg tamoxifen s.c for 5 times, while Group Ctrl received solvent injections. Rats were killed 5 weeks later. Measurements of body weight and length(=nose-anus length) were taken every 3-4 days. Vaginal opening was observed from 4-week age. On the day of sacriface, body weight, body length and left tibial length were measured, plasma were taken for determining E2 level, IGF-1 (IRMA) and IGFBP-3 (IRMA) concentrations; liver samples were taken for detecting GHRmRNA、IGF-1mRNA and IGFBP-3mRNA by real-time RT-PCR; right tibia were fixed, demineralized and processed for paraffin-embedding. Paraffin sections were HE stained for growth plate measurements. IGF-1 and IGF-1R level on growth plate were immunohistochemical localized and image analysed.

Results: 1. Skeletal growth: Tamoxifen decreases both of the body weight and body length without influencing the tibial length. 2. Growth plate HE measurement: Tamoxifen increases the width of PZ[(185.0±12.7μm)VS (172.5±61.0μm), P < 0.05], decrease the width of HZ[(167.5±37.0μm) VS (188.3±33.7μm), P < 0.05] and cell number[(7.2±1.0) VS (8.9±0.6),P < 0.05] in HZ without changing total EGP width[ 358.1±45.0 VS (373.3±35.7μm),P < 0.05].

3. Plasma concentration determination: Tamoxifen does not alter plasma E2 level, decreases plasma IGFBP-3 level(443.8±65.5 ng/ml versus 537.7±94.1 ng/ml, P < 0.05). Tamoxifen does not alter hepatic GHRmRNA, IGF-1mRNA or IGFBP-3mRNA, and does not alter local IGF-1and IGF-1R level on growth plate.

Conclusion: Tamoxifen inhibited growth, especially weight gain and fat accumulation. Besides, tamoxifen has dual effects of anti-estrogen and estrogen-like on the growth plate. So tamoxifen is inapplicable for central precocious puberty treatment. The safety of tamoxifen for peripheral precocious puberty needs to be reevaluated.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

Online,
22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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