Activation of estrogen receptor-alpha induces gonadotroph progesterone receptor expression and action differently in young and middle-aged ovariectomized rats.
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.
Gordon
Ana
A
Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain. anagordonbc@gmail.com
Aguilar
Rafaela
R
Garrido-Gracia
José C
JC
Guil-Luna
Silvia
S
Sánchez-Cespedes
Raquel
R
Millán
Yolanda
Y
Martín de las Mulas
Juana
J
Sánchez-Criado
José E
JE
D000367:Age Factors; D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000502:physiology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D008024:Ligands; D007986:Luteinizing Hormone / Q000378:metabolism; D010052:Ovariectomy; D010636:Phenols; D010902:Pituitary Gland / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology
D047628:Estrogen Receptor alpha; D008024:Ligands; D010636:Phenols; D011720:Pyrazoles; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; C074283:estradiol 3-benzoate; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone