Release of luteinizing hormone-releasing hormone (LHRH) and neuroactive substances in unanesthetized animals as estimated with push-pull cannulae (PPC).

In this report, we have reviewed recent information gathered by probing with a push-pull cannula (PPC) the in vivo activity of the suprachiasmatic nucleus (SCN), hypothalamus, and anterior pituitary gland of freely moving animals. In male and female rats, probing of the SCN with the PPC revealed distinct oscillatory patterns of 5-hydroxy indole-acetic acid (5-HIAA) output very much dependent on the position of the cannula. In males, it was also possible to demonstrate, for the first time, in vivo output of immunoreactive vasopressin (VP) most likely from the SCN. Interestingly, the output of VP was stimulated by local activation of probable 5-hydroxytryptamine (5-HT) terminals with 5-hydroxytryptophan (5-HTP), a precursor of 5-HT synthesis. Probing the hypothalamus of rats and rabbits revealed that the in vivo release of luteinizing hormone-releasing hormone (LHRH) (frequency and amplitude of the LHRH signal) can be altered by administration of estrogen to ovariectomized rats; in both species, progesterone stimulated the amplitude of the LHRH signal, but only when this steroid was infused in pulses--the physiological mode of circulating progesterone in the rat. Further, in male rabbits, pulses of progesterone did not stimulate LHRH release. Last, probing the anterior pituitary with the PPC revealed that a series of push-pull perfusions could be performed in the same animal under different experimental conditions for nearly 60 days of experimentation. It also resolved the apparent paradox that after castration, decreased instead of increased activity of the neural LHRH apparatus was noticed when the PPC was positioned in the hypothalamus. Moving the PPC to the anterior pituitary revealed that castration was accompanied by an increase in the amplitude and frequency of the LHRH signals arriving in the anterior pituitary of castrated male rats. This mode of operation of the LHRH pulse generator is clearly compatible with the mode of luteinizing hormone (LH) release in gonadectomized animals. Finally, based on these results, a hypothetical model of the operation of the LHRH pulse generator has been proposed.