Effect of an intraventricular injection of cyclic AMP on plasma prolactin and LH levels of ovariectomized, estrogen treated rats

To evaluate the possible participation of cyclic nucleotides in the neural control of prolactin and luteinising hormone (LH) release, cannulae were placed in the third ventricle (3rd V) of ovariectomized animals which were treated with estradiol benzoate (Eb) (10 μg s.c.). 48 hr after the Eb injection, substances were injected intraventricularly while the rats were lightly anesthetized with ether and their effect on plasma prolactin and LH was determined by radioimmunoassay. The injection of 4 μl of adenosine 3',5' cyclic monophosphate (cAMP) (0.02 or 0.1 M) or its dibutyryl derivative (DBC) (0.1 M) significantly decreased plasma prolactin 30 and/or 60 min later. The response to cyclic AMP was not potentiated by theophylline. Four μl of the 0.9% NaCl diluent, adenosine 5 monophosphate (5' AMP) (0.1 M), or theophylline (0.02 or 0.04 M) failed to alter plasma prolactin. DBC injected bilaterally into the anterior pituitary (AP) (2 μl into each lobe, 0.05 or 0.1 M) did not decrease plasma prolactin, contrasting with the effect observed after its 3rd V injection. When the volume for intraventricular injections was increased, 10 μl of 0.9% NaCl slightly increased the prolactin concentration, but 10 μl of theophylline (0.02 M) plus cyclic AMP (0.1 M) prevented the increase, and 10 μl of theophylline (0.04 M) alone induced a significant decline in prolactin. None of these treatments altered plasma LH levels. DBC (0.1 M, 10 μl) injected along with theophylline significantly depressed prolactin at 30 and 60 min postinjection and failed to alter plasma LH in 5 animals; however this treatment induced marked behavioral and autonomic changes in 7 animals and these changes were associated with increased plasma LH and prolactin 30 min after injection. The results suggest that cyclic AMP may be involved in the hypothalamic control of prolactin secretion by modifying the output of prolactin inhibiting factor and/or releasing factor to decrease prolactin release. The stimulatory effect of 3rd V DBC in high doses on LH and prolactin release may represent a pharmacological effect or may be related to the stimulation of neurons located at a greater distance from the ventricle.