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  • Title: Activation of estrogen receptor-alpha induces gonadotroph progesterone receptor expression and action differently in young and middle-aged ovariectomized rats.
    Author: Gordon A, Aguilar R, Garrido-Gracia JC, Guil-Luna S, Sánchez-Cespedes R, Millán Y, Martín de las Mulas J, Sánchez-Criado JE.
    Journal: Hum Reprod; 2009 Oct; 24(10):2618-28. PubMed ID: 19574278.
    Abstract:
    BACKGROUND: We attempted to define the effect of estrogen receptor (ER)alpha activation on gonadotroph progesterone receptor (PR) expression (mRNA and protein) and action (GnRH-stimulated and GnRH self-priming) in short- and long-term ovariectomized (OVX) rats. METHODS: Two weeks or 1 year after OVX, rats were injected over 3 days with 125 microg/kg of estradiol benzoate (EB), 7.5 mg/kg of the selective ERalpha agonist propylpyrazole triol (PPT), or 15 mg/kg of the selective ER modulator tamoxifen (TX). Controls were given 0.2 ml oil. The last day of ER analog treatment, half of the rats in each group received 25 mg/kg of progesterone (P). The next day, anterior pituitaries were removed and analyzed for PR-AB mRNA and protein. Gonadotrophin secretion in incubated pituitaries was also measured. RESULTS: (i) PR mRNA expression was higher in young than in middle-aged OVX rats although PR protein was absent in pituitaries from both groups of OVX rats; (ii) activation of ERalpha reduced gonadotroph hypertrophy and increased PR mRNA and protein expression (EB > PPT > TX) more efficiently in young than in middle-aged rats, (iii) ER agonists elicited GnRH-stimulated LH and FSH secretion in young but only FSH secretion in middle-aged OVX rats, (iv) evaluated by peak LH concentrations, GnRH self-priming was observed in both groups of OVX rats and (v) P down-regulated PR protein expression in young, and to a lesser extent, in middle-aged OVX rats, in close association with PR-dependent GnRH self-priming. CONCLUSIONS: Middle-aged OVX rats exhibited clear-cut LH, but not FSH, secretory defects in pituitary sensitivity to estrogen and P.
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