Scientific and commercial pharmacological interest in the role of
galanin and
galanin receptors in the regulation of food intake, energy balance, and
obesity has waned recently, following initial enthusiasm during the 1980-1990s. It has been replaced by efforts to understand the role of newly discovered
peptide systems such as the
hypocretin/
orexins,
melanocortins and
cocaine- and
amphetamine-regulated transcript (CART) and their relationship to the important
hormones,
leptin and
insulin. Thus, while numerous studies have revealed the ability of
galanin to stimulate food intake via actions at sites within the hypothalamus, and shown reliable changes in hypothalamic
galanin synthesis in response to food ingestion; findings including the lack of a '
body weight/
obesity' phenotype in
galanin transgenic mouse strains and a lack of agonists/antagonists for
galanin receptor subtypes have probably served to reduce enthusiasm. However, as more is learnt about the general and
galanin-related neurochemistry of brain pathways involved in feeding, metabolism and
body weight control, the potential importance of
galanin systems is again in focus. Studies of the newly discovered
galanin family
peptide, '
galanin-like peptide' (GALP), highlight the likely role of
galanin peptides and receptors in the physiological coupling of
body weight, adiposity and reproductive function. GALP is produced by a discrete population of neurons within the basomedial arcuate nucleus (and median eminence) that send projections to the anterior paraventricular nucleus and that make close contacts with leutinizing
hormone-releasing
hormone (
LHRH) neurons in basal forebrain. Furthermore, GALP neurons express
leptin receptors and respond to
leptin treatment by increasing their expression of GALP
mRNA. Centrally administered GALP activates
LHRH-immunoreactive neurons and increases plasma LH levels. These findings suggest a direct stimulatory action of endogenous GALP on
gonadotropin secretion via actions within the hypothalamus/basal forebrain, with
leptin actions linking this system to body adipose levels.