Elevated hypothalamic aromatization at the onset of precocious puberty in transgenic female mice hypersecreting human chorionic gonadotropin: Effect of androgens

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:390

Article

Gonzalez, Betina¹  Ratner, Laura D.¹  Scerbo, Maria J.⁵  Di Giorgio, Noelia P.¹  Poutanen, Matti^2,3  Huhtaniemi, Ilpo T.^2,4  Calandra, Ricardo S.¹  Lux-Lantos, Victoria A. R.¹  Cambiasso, Maria J.⁵  Rulli, Susana B.¹ 

[1] Inst Biol & Med Expt CONICET, RA-1428 Buenos Aires, DF, Argentina

[2] Univ Turku, Inst Biomed, Dept Physiol, FIN-20520 Turku, Finland

[3] Univ Turku, Turku Ctr Dis Modeling, FIN-20520 Turku, Finland

[4] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London W12 0NN, England

[5] Univ Nacl Cordoba, Inst Invest Med Mercedes & Martin Ferreyra, INIMEC CONICET, RA-5000 Cordoba, Argentina

关键词: Human chorionic gonadotropin;    Hypothalamic-pituitary-gonadal axis;    Precocious puberty;    Aromatase;    Transgenic mice;   

DOI  :  10.1016/j.mce.2014.04.005

来源: Elsevier

【 摘 要 】

Transgenic female mice overexpressing the alpha- and beta- subunits of human chorionic gonadotropin (hCG alpha beta+) exhibited precocious puberty, as evidenced by early vaginal opening. Chronically elevated hCG in 21-day-old hCG alpha beta+ females stimulated gonadal androgen production, which exerted negative feedback over the endogenous gonadotropin synthesis, and activated the hypothalamic GnRH pulsatility and gene expression. Transgenic females also exhibited elevated hypothalamic aromatization in the preoptic area (POA), which is the sexually-differentiated area that controls the LH surge in adulthood. Ovariectomy at 14 days of age was unable to rescue this phenotype. However, the blockade of androgen action by flutamide from postnatal day 6 onwards reduced the aromatase levels in the POA of hCG alpha beta+ females. Our results suggest that early exposure of females to androgen action during a critical period between postnatal days 6-14 induces sex-specific organizational changes of the brain, which affect the aromatase expression in the POA at the onset of precocious puberty. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

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