Hum. Reprod. Advance Access published online on July 2, 2009
Human Reproduction, doi:10.1093/humrep/dep237
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Activation of estrogen receptor-
induces gonadotroph progesterone receptor expression and action differently in young and middle-aged ovariectomized rats
1 Departments of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain 2 Departments of Comparative Pathology, University of Córdoba, Córdoba, Spain
3 Correspondence address. Section of Physiology, Faculty of Medicine, Avda. Menendez Pidal s/n, 14004 Córdoba, Spain. Tel: +34-957-218283; E-mail: anagordonbc{at}gmail.com
BACKGROUND: We attempted to define the effect of estrogen receptor (ER)
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 µg/kg of estradiol benzoate (EB), 7.5 mg/kg of the selective ER
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 ER
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.
Key words:
progesterone receptor expression/gonadotrophin secretion/GnRH self-priming/tamoxifen/estrogen receptor-
agonists
Submitted on February 12, 2009; resubmitted on April 29, 2009; accepted on June 9, 2009.