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INHIBITORY ACTIVITY OF ANALOGUES OF LUTEINIZING HORMONE‐RELEASING HORMONE (LH‐RH) IN VITRO AND IN VIVO
Author(s) -
FERLAND L.,
LABRIE F.,
SAVARY M.,
BEAULIEU M.,
COY D.H.,
COY E. J.,
SCHALLY A. V.
Publication year - 1976
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1976.tb03836.x
Subject(s) - medicine , endocrinology , chemistry , luteinizing hormone , in vivo , amino acid , phenylalanine , hormone , biology , biochemistry , genetics
SUMMARY Improved inhibitors of LH‐RH are those which, beside removal of the histidine residue at position 2 of LH‐RH, include replacement of glycine at position 6 by a d ‐amino acid. A still better modification is replacement of the histidine residual at position 2 by d ‐phenylalanine. As examples, when tested in pituitary cells in culture, [Des‐His 2 ]LH‐RH, [Des‐His 2 , D‐Leu 6 ] LH‐RH, [Des‐His 2 , D‐Phe 6 ]‐LH‐RH, [D‐Phe 2 ]LH‐RH, [D‐Phe 2 , D‐Leu 6 ]LH‐RH and [D‐Phe 2 , D‐Phe 6 ]LH‐RH inhibit 50% of LH release induced by LH‐RH at molar ratios (MR 50 s) of 3000, 500, 60, 1000, 150 and 25, respectively. [D‐Phe 2 , Phe 5 , D‐Phe 6 ]LH‐RH have MR 50 values of respectively 400, 100, and 75. When evaluated in vivo , some of the mentioned structural modifications permit inhibition of LH‐RH action at molar ratios lower than observed in vitro . At a 500 molar ratio, [D‐Phe 2 , Phe 5 , D‐Phe 6 ]‐LH‐RH inhibits the plasma LH rise induced by LH‐RH by 75% up to 5 h after its injection. When administered at 12.00 hours at the dose of 2 mg, this analogue inhibits the sponatenous pro‐oestrus LH surge and ovulation by 85 and 75%, respectively.