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Leiden University Medical Centre, Department of Pharmacology, Wassenaarseweg 72, 2333-AL Leiden, The Netherlands

(Received 17 November 1977)

The mechanism by which oestrogen can augment the pituitary response to luteinizing hormone releasing hormone (LH-RH) is unknown. A number of studies have suggested that at least part of the action of LH-RH is mediated by cyclic AMP (Ratner, 1970; Borgeat, Chavancy, Dupont, Labrie, Arimura & Schally, 1972; Makino, 1973; Beaulieu, Labrie, Coy, Coy & Schally, 1975). In preliminary experiments we found that the combination of 1 mM-N⁶-monobutyryl cyclic AMP plus 10 mM-theophylline showed maximum activity in causing the release of luteinizing hormone (LH) from the pituitary glands of intact dioestrous rats in vitro, although it only mimicked the action of a relatively low concentration of LH-RH (0·1 ng/ml). We decided to investigate whether the release of LH induced by this combination of monobutyryl cyclic AMP and theophylline could also be augmented by