Submitted January 9, 2007
Returned for revision February 7, 2007
Accepted April 9, 2007
Pituitary
Differential Modulation of Gonadotropin Secretion by
Selective ESR1 and ESR2 Agonists in Ovariectomized Ewes
J. Alejandro Arreguin-Arevalo ,
Tracy L. Davis ,
and
Terry M. Nett *
* To whom correspondence should be addressed. E-mail: terry.nett{at}colostate.edu.
Abstract
The objectives of this study were to determine if activation of ESR1 (also known as ERalpha), 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 (IM) 25 µg estradiol (E2), 12 mg propylpyrazoletriol (PPT; a sub-type selective ESR1 agonist), 21 mg diaprylpropionitrile (DPN; a sub-type selective ESR2 agonist), or PPT + DPN. Like E2, administration of PPT, DPN, or their combination 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 combined, were 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 the positive feedback of E2 on LH secretion, at least partially, 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.
Key words:
Anterior pituitary •
Estradiol •
Estradiol receptor •
Follicle-stimulating hormone •
Luteinizing hormone
