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ANTIGONADOTROPIC DECAPAPTIDE (AGD) SUPPRESSES THE ESTRADIOL (E) INDUCED PREOVULATORY GONADOTROPIN RELEASING HORMONE (GNRH) SURGE IN OVARIECTOMIZED (OVX) EWES.
Warner, Grace1, Moore, Chel1, Sanders, Sara1, Gentry, Paula 2, Wise, Mark2, 1 2
ABSTRACT- AGD has previously been shown to inhibit tonic GnRH/LH release in sheep, cattle and rats. The objective of Exp.1 was to determine the effect of exogenous AGD on the E-induced preovulatory LH surge in OVX ewes. Ewes were fitted with intracerebroventricular cannulae (i.c.v.) ten d after OVX and assigned to one of four treatments: vehicle (control; n=6), 200 mg AGD via i.c.v. at 6 hr (AGD6; n=5), 6 and 12 hr (AGD12; n=4), or 6, 12, and 18 hr (AGD18; n=4) following E administration (hr 0). All ewes were treated with 25 ug E each i.m. and i.v. From -6 to 36 hr, blood samples were collected at 30-minute intervals and LH concentrations measured by RIA. LH surge amplitude was decreased in all AGD groups (11.13, 9.15, and 15.7 ng/ml for AGD6, AGD12, and AGD18, respectively) vs. controls (37.7 ng/ml; p<0.0001). Likewise, AGD decreased area under the curve (AUC; 41.2, 41.9, and 110.97 for AGD6, AGD12, and AGD18, respectively) vs. controls (241.3; p<0.0001). The onset of the LH surge was delayed (p<0.05) in AGD6 ewes and duration shortened (p<0.05) in AGD6 and AGD12 ewes compared to controls; however, in AGD18 ewes, the onset was earlier (p<0.05) while the duration was similar (p>0.1) to controls. Duration of the LH surge was shorter (p<0.05) and surge amplitude and AUC lower (p<0.05) in AGD6 and AGD12 than in AGD18 ewes. The objective of Exp.2 was to determine if endogenous AGD inhibition could be blocked by AGD antisense oligonucleotides (ASODN). As before, ewes were given 50 mg E at hr 0. Ewes were infused with 200 ng/ml/min AGD ASODN or sense ODN (control) i.c.v. starting at 0 hr for 36 hrs. ASODN increased surge amplitude by 75.9% (p<0.05) and AUC by 40.9% (p<0.05) but did not affect the time of onset or duration of the LH surge (p>0.1). Given that exogenous AGD inhibits the LH surge and ASODN removes the inhibition of endogenous AGD, these results indicate that AGD may influence the magnitude of the E-induced preovulatory LH surge.
KEY WORDS: AGD, GnRH, LH, Estradiol
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