Immunolesions of Glucoresponsive Projections to the Arcuate Nucleus Alter Glucoprivic-Induced Alterations in Food Intake, Luteinizing Hormone Secretion, and GALP mRNA, but Not Sex Behavior in Adult Male Rats

Abstract

Metabolic signals such as insulin, leptin and glucose are known to alter hypothalamic function. Although insulin and leptin are known to directly alter hypothalamic areas that regulate reproduction, the mechanisms by which glucose alters reproductive function are not as clear. Catecholaminergic neurons in the A1/C1 region in the hindbrain are glucose-responsive and project to the arcuate nucleus. To determine if this pathway is involved in the regulation of sex behavior and luteinizing hormone (LH) secretion, this catecholaminergic pathway was lesioned with injections of saporin conjugated with anti-dopamine-β-hydroxylase (DSAP) or unconjugated saporin (SAP) in adult male rats. Rats were given glucoprivic challenges and feeding and sex behavior was observed. As was expected, the DSAP-treated rats showed decreased feeding during glucoprivation (250 mg/kg 2-deoxy-D-glucose, 2DG) compared to SAP controls. Glucoprivation caused a significant reduction in sex behavior in both SAP and DSAP animals equally, compared to saline treatments (p < 0.05). At the end of the experiment, animals were given a final challenge with 2DG or saline, euthanized by decapitation and trunk blood was assayed for plasma LH levels. In situ hybridization analysis revealed that 2DG treatment caused a significant reduction in GALP mRNA in SAP controls compared to saline treatment. This reduction in GALP mRNA was prevented with DSAP treatment. In SAP animals, 2DG elicited a significant decrease in plasma LH levels (p < 0.05); this reduction in plasma LH was absent in the DSAP-treated male rats. These data indicate that the A1/C1 efferents to the ventromedial hypothalamus are involved in the glucostatic regulation of GALP mRNA, feeding behavior and LH secretion, but not sex behavior in the adult male rat.

Sex differences in the effect of prepubertal GALP infusion on growth, metabolism and LH secretion

“…Alternatively, the time course of GALP appearance in the Arc is similar to that reported by others for hindbrain catecholaminergic innervation of the ventromedial hypothalamus [39,40]. A recent report demonstrated that GALP gene expression is also regulated by catecholaminergic afferents from the hindbrain [30]. It is possible that GALP gene expression is initially triggered by the appearance of hindbrain catecholaminergic neurons in the hypothalamus.…”

“…In adult rats, GALP is expressed in the Arc of the hypothalamus and GALP gene expression is regulated by leptin, insulin, and metabolic fuels [6,30,31]. Our study has shown that in neonatal rats, GALP gene expression does not appear until late postnatally (~PND12).…”

Galanin-like peptide: a key player in the homeostatic regulation of feeding and energy metabolism?

“…46 These findings suggest that GALP mRNA in the pituicytes is controlled by thyroid hormone, and that GALP mRNA is physiologically associated with the activation of oxytocin-and vasopressin-secreting neurons during lactation. 46 Catecholaminergic neurons in the A1/C1 region in the medulla oblongata are glucose responsive and project to the ARC, 47 and A1/C1 efferents to the hypothalamus are involved in the glucostatic regulation of GALP mRNA, feeding behavior and LH secretion. 47 …”

“…46 Catecholaminergic neurons in the A1/C1 region in the medulla oblongata are glucose responsive and project to the ARC, 47 and A1/C1 efferents to the hypothalamus are involved in the glucostatic regulation of GALP mRNA, feeding behavior and LH secretion. 47 …”

“…Thus, it is possible that GALP has a physiologically important role in anorexigenic action. 18,47 Interestingly, GALP can be detected in the general circulation, and fasting decreases both plasma levels and GALP influx into the brain. 12 These findings suggest that GALP conveys a satiety signal from peripheral organs to brain, although there are few studies mentioning the presence of GALP-producing cells in the peripheral organs.…”