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Journal of Endocrinology (2007) 193, 107-119       DOI: 10.1677/JOE-06-0214
© 2007 Society for Endocrinology
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The integrated action of oestrogen receptor isoforms and sites with progesterone receptor in the gonadotrope modulates LH secretion: evidence from tamoxifen-treated ovariectomized rats

José C Garrido-Gracia*, Ana Gordon*, Carmina Bellido, Rafaela Aguilar, Inmaculada Barranco1, Yolanda Millán1, Juana Martín de las Mulas1 and José E Sánchez-Criado

Departments of Cell Biology, Physiology and Immunology and
1 Comparative Pathology, University of Córdoba, Córdoba, Spain

(Requests for offprints should be addressed to J E Sánchez-Criado who is now at Sección de Fisiología, Facultad de Medicina, Avda. Menendez Pidal s/n, 14004 Córdoba, Spain; Email: fi1sacrj{at}uco.es)

* (J C Garrido-Gracia and A Gordon contributed equally to this work.)

The specific role of each oestrogen receptor (ER) isoform ({alpha} and ß ) and site (nucleus and plasma membrane) in LH release was determined in ovariectomized (OVX) rats injected over 6 days (days 15–20 after OVX) with a saturating dose (3 mg/day) of tamoxifen (TX), a selective ER modulator with nuclear ER{alpha} agonist actions in the absence of oestrogen. This pharmacological effect of TX was demonstrated by the fact that it was blocked by the selective ER{alpha} antagonist methyl-piperidinopyrazole. Over the past 3 days of the 6-day TX treatment, rats received either 25 µg/day oestradiol benzoate (EB), 1.5 mg/day selective ER{alpha} agonist propylpyrazole triol (PPT) and the selective ERß agonist diarylpropionitrile (DPN), or a single 3 mg injection of the antiprogestin onapristone (ZK299) administered on day 20. Blood samples were taken to determine basal and progesterone receptor (PR)-dependent LH-releasing hormone (LHRH)-stimulated LH secretion and to evaluate LHRH self-priming, the property of LHRH that increases gonadotrope responsiveness to itself. Blood LH concentration was determined by RIA and gonadotrope PR expression by immunohistochemistry. Results showed that i) EB and DPN potentiated the negative feedback of TX on basal LH release; ii) DPN reduced TX-induced PR expression; iii) EB and PPT blocked TX-elicited LHRH self-priming and iv) ZK299 reduced LHRH-stimulated LH secretion and blocked LHRH self-priming. These observations suggest that oestrogen action on LH secretion in the rat is exerted at the classic ER{alpha} pool and that this action might be modulated by both ERß and membrane ER{alpha} through their effects on PR expression and action respectively.




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