Colocalization of galanin and luteinizing hormone-releasing hormone in a subset of preoptic hypothalamic neurons: anatomical and functional correlates.

Abstract

Colocalization of neurotransmitters, including neuropeptides and amines, in the same neuron of certain areas or well-defined nuclei of the central and peripheral nervous systems appears to be the rule rather than the exception. The coexistent neurotransmitters can be coreleased and interact at pre-and postsynaptic levels in a synergistic or antagonistic manner. Galanin is a recently isolated and characterized "gut-brain" peptide. It is colocalized with many neurotransmitters in both the central and the peripheral nervous systems. Among other regions in the central nervous system, galanin is present in neuronal perikarya of the septum and the hypothalamus. The dense accumulation of nerve terminals in the external zone of the median eminence suggests that galanin is an important peptide regulating neuroendocrine functions. Although most galanin and luteinizing hormonereleasing hormone (LHRH) neurons have a distinctly different morphology, a subset of galanin-immunoreactive perikarya in the diagonal band of Broca and the medial preoptic area, near the organum vasculosum of the lamina terminalis, have morphological features similar to those of LHRH neurons. By using double-labeling immunocytochemistry, we have found that in the preoptic region of the male rat brain 15-20% of these "LHRH-like" galanin-immunoreactive neurons are also immunopositive for LHRH. Moreover, in the medial preoptic area and the diagonal band of Broca, some of the single-labeled LHRH cells are surrounded with galanin-immunoreactive nerve terminals, suggesting that LHRH perikarya have synaptic contacts with galanin-immunoreactive terminals. Additional studies indicated that galanin can readily enhance in vitro release of LHRH from nerve terminals in the median eminence.The observations that (i) galanin is coexpressed with LHRH, (ii) galanin seems to innervate LHRH-producing neurons, and (iii) galanin acts as a putative neurotransmitter to enhance the release of LHRH suggest that galanin should be considered an important regulator of LHRH-containing neurons and, therefore, of reproductive functions.Galanin is a 29-amino acid peptide originally isolated from porcine intestine (1). It is widely distributed in the central and peripheral nervous systems (2-5), the gastrointestinal tract (2, 6, 7), the urogenital tract (8), and the adrenal medulla (9). Moreover, a widespread distribution of galanin binding sites in the nervous system has also been described (10). Immunocytochemical mapping of galanin-immunoreactive structures in the brain indicated that high galanin concentrations occur in the median eminence (ME); in the paraventricular, the supraoptic, the arcuate, and the dorsomedial nuclei of the hypothalamus; in the locus ceruleus; in the spinal trigeminal nucleus; and in the nucleus of the solitary tract (1-4).Although the precise physiological role of galanin has not yet been established, the presence of a dense accumulation of galanin-immunoreactive nerve terminals in the external zone of the ME suggests that galanin is an important h...

Physiologic Regulation of a Tetrodotoxin-Sensitive Sodium Influx That Mediates a Slow Afterdepolarization Potential in Gonadotropin-Releasing Hormone Neurons: Possible Implications for the Central Regulation of Fertility

“…3C,D). A high percentage of GnRH neurons coexpress galanin (Merchenthaler et al, 1990;Hohmann et al, 1998) and galanin receptor is also expressed in these neurons (Mitchell et al, 1999), but blocking galanin receptors was also without effect on the sADP (n ϭ 8) (Fig. 3D).…”

Effects of cycle stage on regionalised galanin, galanin receptors 1–3, GNRH and GNRH receptor mRNA expression in the ovine hypothalamus

“…This study extends previous work by showing that the hypothalamic areas that contain galanin and GNRH mRNA also express mRNA for the three GalRs and, thus, provide the mechanistic links required for galanin to be able to regulate GNRH secretion. Such a role for galanin had previously been proposed given the presence of GalR1 mRNA containing cells in regions of the hypothalamus that contain GNRH (Faure-Virelizier et al 1998, Landry et al 1998, Dufourny & Skinner 2004, Chambers et al 2007 and the observation that galanin is co-expressed within GNRH neurons in rodents (Coen et al 1990, Merchenthaler et al 1990) and sheep (Dufourny et al 2003). While the results of this study indicate GalR2 mRNA expression in these same hypothalamic nuclei, as we have previously shown that E 2 -responsive hypothalamic cells that are immunopositive for GalR2, do not co-localise with GNRH in the sheep (Chambers et al 2007), direct regulatory effects of galanin on GNRH secretion are unlikely to be mediated by GalR2.…”

“…GalR1 and GalR3 are known to activate Gi proteins and are typically considered inhibitory, while GalR2, which is associated with Go/q/11 proteins, is considered stimulatory. Given the reported distribution of galanin (Melander et al 1986, Skofitsch & Jacobowitz 1986) and its membranebound receptors (GalR1, GalR2 and GalR3; Wang et al 1997, Smith et al 1998, Waters & Krause 2000 within the hypothalamus and pituitary gland, roles both as a neurotransmitter and as a neuromodulator have been proposed , Merchenthaler et al 1990, Cheung et al 1996, Gajewska et al 2004, Merchenthaler 2005. Specifically, it has been hypothesised that galanin could play a role in oestrogen's positive feedback effects on gonadotropin-releasing hormone/luteinising hormone secretion, as its expression is positively regulated by oestrogen (Shen et al 1998).…”

Inhibition of Steroid‐Induced Galanin mRNA Expression in GnRH Neurons by Specific NMDA‐Receptor Blockade

“…Galanin is expressed in a variety of neurons throughout the brain, including any agent that blocks the LH surge should also prevent the induction of galanin mRNA in GnRH neurons. We tested this GnRH neurons (3)(4)(5). While the specific role that galanin plays in the generation of an LH surge is unknown, its importance is hypothesis by investigating the effects of MK801, an N-methyl-D-aspartate (NMDA) receptor antagonist, on the induction of underscored by the observation that galanin antibodies and the galanin R1 receptor antagonist, galantide, inhibit the GnRH/LH galanin mRNA in GnRH neurons.…”