Antagonistic activity of analogs of luteinizing hormone-releasing hormone (LH-RH) in vitro

D. H. Coy; F. Labrie; M. Savary; E. J. Coy; A. V. Schally

doi:10.1016/0303-7207(76)90083-6

Antagonistic activity of analogs of luteinizing hormone-releasing hormone (LH-RH) in vitro

D. H. Coy, F. Labrie, M. Savary, E. J. Coy, A. V. Schally

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

The ability of eighteen analogs of LH-RH to inhibit LH-RH-induced LH release was tested in primary cultures of rat anterior pituitary cells. [Des-His²]LH-RH, [Des-His², D-Leu⁶]LH-RH and [Des-His², D-Phe⁶]LH-RH inhibited 50% of LH-RH-induced LH release at molar ratios (MR₅₀s) of 3000, 500 and 60, respectively, while [D-Phe²]LH-RH, [D-Phe², D-Leu⁶]LH-RH and [D-Phe², D-Phe⁶]LH-RH had similar effects at MR₅₀s of 1000, 150 and 25, respectively. This indicates that substitution of D-phenylalanine for histidine at position 2 of LH-RH leads to compounds approximately 3-fold more potent than the corresponding [Des-His²]-analogs. [D-Phe², D-Phe⁶]LH-RH, the most potent antagonist tested has however a slight agonistic activity (0.003% that of LH-RH itself). [D-Phe², D-Phe⁶, Phe⁷]LH-RH, [D-Phe², Phe³, D-Phe⁶]-LH-RH and [D-Phe², Phe⁵, D-Phe⁶]LH-RH inhibit 50% of LH-RH action at MR₅₀s of 400, 100 and 75, respectively. All of the analogs mentioned in the last group have LH-releasing activities below 1/100,000 that of LH-RH itself.

Original language	English (US)
Pages (from-to)	201-208
Number of pages	8
Journal	Molecular and Cellular Endocrinology
Volume	5
Issue number	3-4
DOIs	https://doi.org/10.1016/0303-7207(76)90083-6
State	Published - Jan 1 1976
Externally published	Yes

Keywords

antagonistic analogs
cell culture
LH
pituitary

ASJC Scopus subject areas

Endocrinology
Endocrinology, Diabetes and Metabolism

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@article{68b12c82044c46619108631e25e0923c,

title = "Antagonistic activity of analogs of luteinizing hormone-releasing hormone (LH-RH) in vitro",

abstract = "The ability of eighteen analogs of LH-RH to inhibit LH-RH-induced LH release was tested in primary cultures of rat anterior pituitary cells. [Des-His2]LH-RH, [Des-His2, D-Leu6]LH-RH and [Des-His2, D-Phe6]LH-RH inhibited 50% of LH-RH-induced LH release at molar ratios (MR50s) of 3000, 500 and 60, respectively, while [D-Phe2]LH-RH, [D-Phe2, D-Leu6]LH-RH and [D-Phe2, D-Phe6]LH-RH had similar effects at MR50s of 1000, 150 and 25, respectively. This indicates that substitution of D-phenylalanine for histidine at position 2 of LH-RH leads to compounds approximately 3-fold more potent than the corresponding [Des-His2]-analogs. [D-Phe2, D-Phe6]LH-RH, the most potent antagonist tested has however a slight agonistic activity (0.003% that of LH-RH itself). [D-Phe2, D-Phe6, Phe7]LH-RH, [D-Phe2, Phe3, D-Phe6]-LH-RH and [D-Phe2, Phe5, D-Phe6]LH-RH inhibit 50% of LH-RH action at MR50s of 400, 100 and 75, respectively. All of the analogs mentioned in the last group have LH-releasing activities below 1/100,000 that of LH-RH itself.",

keywords = "antagonistic analogs, cell culture, LH, pituitary",

author = "Coy, {D. H.} and F. Labrie and M. Savary and Coy, {E. J.} and Schally, {A. V.}",

year = "1976",

month = jan,

day = "1",

doi = "10.1016/0303-7207(76)90083-6",

language = "English (US)",

volume = "5",

pages = "201--208",

journal = "Molecular and Cellular Endocrinology",

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TY - JOUR

T1 - Antagonistic activity of analogs of luteinizing hormone-releasing hormone (LH-RH) in vitro

AU - Coy, D. H.

AU - Labrie, F.

AU - Savary, M.

AU - Coy, E. J.

AU - Schally, A. V.

PY - 1976/1/1

Y1 - 1976/1/1

N2 - The ability of eighteen analogs of LH-RH to inhibit LH-RH-induced LH release was tested in primary cultures of rat anterior pituitary cells. [Des-His2]LH-RH, [Des-His2, D-Leu6]LH-RH and [Des-His2, D-Phe6]LH-RH inhibited 50% of LH-RH-induced LH release at molar ratios (MR50s) of 3000, 500 and 60, respectively, while [D-Phe2]LH-RH, [D-Phe2, D-Leu6]LH-RH and [D-Phe2, D-Phe6]LH-RH had similar effects at MR50s of 1000, 150 and 25, respectively. This indicates that substitution of D-phenylalanine for histidine at position 2 of LH-RH leads to compounds approximately 3-fold more potent than the corresponding [Des-His2]-analogs. [D-Phe2, D-Phe6]LH-RH, the most potent antagonist tested has however a slight agonistic activity (0.003% that of LH-RH itself). [D-Phe2, D-Phe6, Phe7]LH-RH, [D-Phe2, Phe3, D-Phe6]-LH-RH and [D-Phe2, Phe5, D-Phe6]LH-RH inhibit 50% of LH-RH action at MR50s of 400, 100 and 75, respectively. All of the analogs mentioned in the last group have LH-releasing activities below 1/100,000 that of LH-RH itself.

AB - The ability of eighteen analogs of LH-RH to inhibit LH-RH-induced LH release was tested in primary cultures of rat anterior pituitary cells. [Des-His2]LH-RH, [Des-His2, D-Leu6]LH-RH and [Des-His2, D-Phe6]LH-RH inhibited 50% of LH-RH-induced LH release at molar ratios (MR50s) of 3000, 500 and 60, respectively, while [D-Phe2]LH-RH, [D-Phe2, D-Leu6]LH-RH and [D-Phe2, D-Phe6]LH-RH had similar effects at MR50s of 1000, 150 and 25, respectively. This indicates that substitution of D-phenylalanine for histidine at position 2 of LH-RH leads to compounds approximately 3-fold more potent than the corresponding [Des-His2]-analogs. [D-Phe2, D-Phe6]LH-RH, the most potent antagonist tested has however a slight agonistic activity (0.003% that of LH-RH itself). [D-Phe2, D-Phe6, Phe7]LH-RH, [D-Phe2, Phe3, D-Phe6]-LH-RH and [D-Phe2, Phe5, D-Phe6]LH-RH inhibit 50% of LH-RH action at MR50s of 400, 100 and 75, respectively. All of the analogs mentioned in the last group have LH-releasing activities below 1/100,000 that of LH-RH itself.

KW - antagonistic analogs

KW - cell culture

KW - LH

KW - pituitary

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JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

IS - 3-4

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