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  • Title: Action of inhibitory LH-RH analogs in rat pituitary and luteal cell cultures.
    Author: Spona J, Müntz R, Nicolics K, Seprödi J, Teplan I.
    Journal: Endocrinol Exp; 1984 Jun; 18(2):101-7. PubMed ID: 6378589.
    Abstract:
    The effect of LH-RH antagonists on LH-RH stimulated LH release was studied in primary rat pituitary cell culture and the inhibition by LH-RH antagonists of HCG provoked progesterone production was investigated in primary rat luteal cell culture. Antagonists used in this study were Ac-D-Trp1, D-Phe(Cl)2, D-Lys6, D-Ala10-LH-RH(I1) and the respective D-Lys6 isophthaloyl dimer (I2). LH-RH activity was noted to be reduced to 1/12 by I1 and to 1/23 by I2 in the pituitary cell culture system. The LH-RH inhibitors did not possess intrinsic LH releasing activity up to 10(-6) mol 1(-1). Incubation of rat luteal cells with HCG in the presence of LH-RH, I1 or I2 resulted in a smaller progesterone release than that observed in the absence of the peptides. ED50 of HCG was noted to be 5.7 X 10(-13) mol 1(-1) and 10(-8) mol 1(-1) LH-RH, I1 or I2 caused a shift of ED50 to 6.3 X 10(-12) mol 1(-1), 1.2 X 10(-12) mol 1(-1) and 7.9 X 10(-13) mol 1(-1), respectively. The present investigation is the first demonstration of reduction by LH-RH antagonists of gonadal steroid production. The present results suggest the use of such inhibitory LH-RH analogs in the treatment of hormone dependent tumors such as prostatic carcinoma and would not cause a transient rise of gonadal steroids as seen by the use of LH-RH agonists.
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