Tl. Horvath et al., MORPHOLOGICAL AND PHARMACOLOGICAL EVIDENCE FOR NEUROPEPTIDE Y-GALANININTERACTION IN THE RAT HYPOTHALAMUS, Endocrinology, 137(7), 1996, pp. 3069-3077
Galanin (GAL) and neuropeptide Y (NPY) have been shown to play importa
nt roles in the regulation of pituitary hormone secretion, as well as
ingestive and sexual behaviors, by acting within the hypothalamus. Whi
le the mechanism of action of these regulatory peptides is under inten
sive investigation, less attention has been paid to the possible inter
action between them in influencing these central regulatory processes.
Because NPY and GAL augment pituitary gonadotropin release, the prese
nt study was undertaken to evaluate the nature of morphological and fu
nctional relationships between these excitatory hypothalamic peptiderg
ic systems. Double immunolabeling for NPY and GAL was carried out on v
ibratome sections taken from the hypothalamus of colchicine-pretreated
female rats. Avidin-biotin peroxidase technique and a dark blue diami
nobenzidine reaction was used to visualize NPY profiles, while the GAL
neurons were labeled with a light brown diaminobenzidine reaction usi
ng either the avidin-biotin peroxidase or the peroxidase antiperoxidas
e technique. Light microscopic examination of the immunostained materi
al showed that in the arcuate nucleus, paraventricular nucleus, suprao
ptic nucleus, anterior hypothalamus, and medial preoptic area, an abun
dant network of NPY-immunoreactive axone surrounded GAL-immunostained
cells. Numerous dark blue NPY-containing putative boutons were observe
d in close proximity to GAL-immunolabeled cell bodies and dendrites. C
orrelated light and electron microscopic examination revealed that mos
t of the immunoreactive NPY axon terminals established synaptic connec
tions with GAL-expressing cells. Synaptic connections were most freque
ntly found in the medial preoptic area and in the magnocellular region
of the paraventricular nucleus and arcuate nucleus. Fewer connections
were observed in the supraoptic nucleus. These morphological observat
ions demonstrate the existence of a strong NPY input to hypothalamic G
AL neurons, thereby suggesting a modulatory role for NPY in monitoring
GAL release. To evaluate the functional relevance of this anatomical
relationship, the effects of intraventricular injection of a GAL recep
tor antagonist, galantide, were examined on NPY-induced LH release in
ovarian steroid-primed ovariectomized rats. As expected, intraventricu
lar injection of NPY readily stimulated LH release. Although, while on
its own, galantide was ineffective in altering basal LH release, it m
arkedly attenuated the NPY-induced LH response, thereby suggesting tha
t GAL released in response to NPY administration may, in part, mediate
the excitatory effects of NPY. These experimental results, taken toge
ther with the morphological observations, document the involvement of
an NPY --> GAL signaling modality in the release of gonadotropins and,
likewise, raise the possibility of a similar signaling process in the
release of other pituitary hormones and elicitation of behavioral eff
ects attributed to NPY and GAL.