ESPE Abstracts (2015) 84 P-3-1132

Puberty

Effects of GnRH Agonists and Antagonists on Danazol-Induced Precocious Puberty Rat

Aram Yang, Rimm Huh, Jinsup Kim, Sung Yoon Cho & Dong-Kyu Jin

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Samsung Medical Center, Seoul, Republic of Korea


Background: GnRH agonists are a common treatment modality for patients with central precocious puberty.

Objective and hypotheses: Danazol-induced precocious puberty rats were used as an animal model to compare the effects of GnRH analogues and to assess combinations of treatment with agonistic and antagonistic GnRH analogues.

Method: A 5-day-old female Sprague–Dawley rats were subcutaneously injected with a single dose of 300 μg danazol. After vaginal opening, the rats were injected daily for 5 days with a combination of GnRH agonists (triptorelin) and antagonists (cetrorelix acetate). Serum levels of LH and FSH were obtained on days 2, 5, and 15 of treatment.

Results: Rats treated with danazol showed significant advancement in vaginal opening compared with WT rats (P=0.000 respectively). LH and FSH inhibition was strongest after 2-day treatment with antagonist alone (LH 1.07±0.04 ng/ml vs 1.25±0.08 ng/ml in controls, P=0.004 and FSH 0.39±0.03 ng/ml vs 0.55±0.09 ng/ml in controls, P=0.006). Antagonist for 2-day followed with combined agonist/antagonist had the second lowest levels of LH and FSH, though not statistically significant (after 5-day treatment, LH 1.09±0.05 ng/ml vs 1.17±0.04 ng/ml in controls, P=0.33 and FSH 0.46±0.04 ng/ml vs 0.47±0.07 ng/ml in controls, P=0.7). Agonist only group showed significant increase of LH and FSH after 5-day of treatment (LH 2.27±0.08 ng/ml vs 1.17±0.04 ng/ml in controls, P<0.0001 and FSH 2.91±0.65 ng/ml vs 0.47±0.07 ng/ml in controls, P=0.0008).

Conclusion: Combination of GnRH agonist with antagonist, and especially treatment with antagonist alone seems to suppress gonadotropin levels most sufficiently. The danazol treated rat model proved to be a model of true precocious puberty; further related studies involving this animal model should be considered.

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