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The relative potencies of seven antagonists of LH-RH to inhibit LH-RH-induced cyclic AMP accumulation and LH and FSH release were measured using rat hemipituitaries in vitro. At appropriate concentrations, [Des-His2, D-Ala6] LH-RH, [Des-His2, D-Ala6, des-Gly-NH210] LH-RH ethylamide, [Des-His2, D-Leu6] LH-RH, [D-Phe2] LH-RH, [Des-His2, Des-Gly-NH210] LH-RH propylamide, [D-Phe2, D-Leu6] LH-RH and [D-Phe2, D-Phe6] LH-RH led to parallel inhibition of cyclic AMP accumulation and LH and FSH release. [D-Phe2, D-Leu6] LH-RH and [D-Phe2, D-Phe6] LH-RH can inhibit 50% of LH-RH action at molar ratios of 100 and 30, respectively. These findings of parallel changes of cyclic AMP levels and LH and FSH release add strong support to the already obtained evidence for a mediator role of the adenylate cyclase system in the action of LH-RH in the anterior pituitary gland.
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