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      Inhibitory Effect of a Highly Potent Antagonist of LH Releasing Hormone (SB-75) on the Pituitary Gonadal Axis in the Intact and Castrated Rat

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          The biological potency of the new, highly potent antagonist [AC-D-Nal (2)<sup>1</sup>, E-Phe(4Cl)<sup>2</sup>, D-Pal(3)<sup>3</sup>, E > -Cit<sup>6</sup>, D-Ala<sup>10</sup>] LH-RH (SB-75) on the pituitary-gonadal system of female castrated and intact ovulating rats was tested. Administration of a single dose (50-100 µg/kg BW) of the antagonist SB-75 inhibited effectively the elevated gonadotrophin levels for 48 h. Pituitary LH and FSH content was not affected by SB-75 treatment. When administered in the early afternoon of the proestrus to intact cycling rats, SB-75 blocked the preovulatory LH surge as well as the primary and secondary FSH surges. However, the secondary FSH surge was not affected by SB-75 treatment when administered on the evening of proestrus suggesting its independence from the LH-RH mechanism. A group of ovariectomized rats was chronically treated with D-Trp<sup>6</sup>-LH-RH after having been pretreated by administration of a single dose of the antagonist. The initial stimulatory release of LH and FSH initiated by injection of the LH-RH agonist was significantly reduced by pretreatment with the LH-RH antagonist. We conclude that the LH-RH antagonist SB-75 may be used effectively in the field of reproductive dysfunction and endocrinological oncology and may become an invaluable physiological probe in studying the hormonal dynamics of the reproductive endocrine axis.

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          Author and article information

          S. Karger AG
          08 April 2008
          : 58
          : 2
          : 153-159
          aTimsit Institute of Reproductive Endocrinology, Sourasky Medical Center of Tel Aviv, and Faculty of Medical Sciences, Tel Aviv University, Tel Aviv, Israel; bTulane University Medical Center and VA Medical Center, New Orleans, La., USA
          126527 Neuroendocrinology 1993;58:153–159
          © 1993 S. Karger AG, Basel

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          Pages: 7
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