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This Article Full Text Full Text (PDF) All Versions of this Article: 77/2/320    most recent biolreprod.107.060046v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Arreguin-Arevalo, J. A. Articles by Nett, T. M. Search for Related Content PubMed PubMed Citation Articles by Arreguin-Arevalo, J. A. Articles by Nett, T. M. Agricola Articles by Arreguin-Arevalo, J. A. Articles by Nett, T. M.

Differential Modulation of Gonadotropin Secretion by Selective Estrogen Receptor 1 and Estrogen Receptor 2 Agonists in Ovariectomized Ewes¹

Department of Biomedical Science, Colorado State University, Fort Collins, Colorado 80523

ABSTRACT

The objectives of this study were to determine whether activation of estrogen receptor 1 (ESR1; also known as ERalpha), or estrogen receptor 2 (ESR2; also known as ERbeta), or both are required to: 1) acutely inhibit secretion of LH, 2) induce the preovulatory-like surge of LH, and 3) inhibit secretion of FSH in ovariectomized (OVX) ewes. OVX ewes (n = 6) were administered intramuscularly 25 micrograms estradiol (E₂), 12 mg propylpyrazoletriol (PPT; a subtype-selective ESR1 agonist), 21 mg diaprylpropionitrile (DPN; a subtype-selective ESR2 agonist), or PPT + DPN. Like E₂, administration of PPT, DPN, or combination of the two rapidly decreased (P < 0.05) secretion of LH. Each agonist induced a gradual, prolonged rise in secretion of LH after the initial inhibition, but neither agonist alone nor the combined agonists was able to induce a "normal" preovulatory-like surge of LH similar to that induced by E₂. Compared with E₂-treated ewes, the beginning of the increase in secretion of LH occurred earlier (P < 0.01) in DPN-treated ewes, later (P < 0.05) in PPT-treated ewes, and at a similar interval in ewes receiving the combined agonist treatment. Like E₂, PPT decreased (P < 0.05) secretion of FSH, but the duration of suppression was much longer in PPT-treated ewes. DPN did not alter secretion of FSH in this study. Modulation of the number of GnRH receptors by PPT and DPN was examined in primary cultures of ovine pituitary cells. In our hands, both PPT and DPN increased the number of GnRH receptors, but the dose of DPN required to stimulate synthesis of GnRH receptors was 10 times higher than that of PPT. We conclude that in OVX ewes: 1) ESR1 and ESR2 mediate the negative feedback of E₂ on secretion of LH at the level of the pituitary gland, 2) ESR1 and ESR2 do not synergize or antagonize the effects of each other; however, they do interact to synchronize the beginning of the stimulatory effect of E₂ on secretion of LH, 3) ESR1 and ESR2 may mediate at least partially the positive feedback of E₂ on LH secretion by increasing the number of GnRH receptors, and 4) only ESR1 appears to be involved in the negative feedback of E₂ on secretion of FSH.

anterior pituitary,, estradiol,, estradiol receptor subtypes,, follicle-stimulating hormone,, luteinizing hormone

¹Supported by National Research Initiative Competitive Grant no. 2005-35203-15376 from the United States Department of Agriculture Cooperative State Research, Education, and Extension Service.

Correspondence: ²Terry M. Nett, Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Science, 3801 West Rampart Rd., Fort Collins, CO 80523-1683. FAX: 970 491 3557; e-mail: Terry.Nett{at}colostate.edu