Galanin is a peptide originally isolated from porcine intestine and shown to be vastly distributed in the central nervous system. The recent availability of the synthetic rat molecule allowed us to generate a specific antiserum against rat galanin. In initial studies from our lab, we observed that a subset of rat galanin-immunoreactive neurons in the preoptic area of the hypothalamus presented a morphology and location similar to that of LHRH-immunoreactive neurons. In fact, these GAL-immunoreactive neurons also expressed LHRH immunoreactivity. This observation suggested to us that GAL could be an important factor in regulating gonadal functions. Using an incubation system [arcuate nucleus-- median eminence (AN-ME) fragments] developed and characterized in our lab, we observed that, indeed, rat galanin was able to potently stimulate LHRH release from AN-ME terminals in vitro. This stimulatory action was linked to PGE2 release since the blockade of PG synthesis using indomethacin, a cyclooxygenase inhibitor, abolished rGAL-induced LHRH release. Moreover, rGAL-induced LHRH release requires a functional noradrenergic system to be expressed since an a adrenergic antagonist, phentolamine, as well as a specific alpha1-adrenergic antagonist, prazosin, were able to block rGAL-induced LHRH release. These anatomical and functional correlates, indicated to us that GAL and LHRH could be also co-secreted. Indeed, when we analyzed rGAL and LHRH release into the hypophyseal portal circulation it was observed that rGAL is released into the portal circulation in higher concentrations than those observed in peripheral blood. Furthermore, rGAL secretion into the portal blood occurred in a pulsatile fashion, depicting secretory events that coincided with those of LHRH. However, it must be noted that practically all rGAL secretory episodes preceded those of LHRH, suggesting that in the generation of a LHRH pulse GAL may be the trigger. These observations provide the basis for considering GAL as a hypothalamic factor participating in the regulation of LHRH release and, thereby, the control of gonadal functions.
