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

Abstract

Sex differences in the effect of prepubertal GALP infusion on growth, metabolism and LH secretion, Physiol. Behav. XX(XX): XXX. The hypothalamic neuropeptide, galanin-like peptide (GALP), is known to have an effect on energy expenditure and reproduction in adult male rats, but little work has been done on prepubertal rats. We hypothesized that hypothalamic GALP is involved in physiological changes associated with the onset of puberty. To test this hypothesis, we first determined the postnatal ontogeny of GALP gene expression via in situ hybridization of developing male and female rat pups through adulthood. GALP gene expression was not observed in either male or female rat pups until after postnatal day (PND) 10 and did not reach adult-like levels until after weaning (PND25). To determine if exogenous GALP could induce the onset of puberty, PND25 male and female rats were implanted with lateral ventricular cannulas connected to an osmotic minipump that delivered either GALP or vehicle. GALP infusion significantly (p < 0.05) increased body weight, food intake, and metabolic rate in male but not female rats compared to control infusion. After two weeks, GALP infusion had no significant effect on the onset of puberty, percent body fat, nor plasma levels of insulin, FSH or gonadal steroids in either sex; however, GALP did significantly (p < 0.05) increase plasma levels of LH and leptin in male but not female rats and increased plasma growth hormone (GH) in both sexes. Our observations further demonstrate a sex difference in GALP responsiveness in prepubertal rats. These data suggest that GALP may be involved with the prepubertal increase in circulating leptin, LH, and GH resulting in an increase in metabolic rate and lean growth associated with puberty.

Rat RFRP-3 Alters Hypothalamic GHRH Expression and Growth Hormone Secretion but Does Not Affect KiSS-1 Gene Expression or the Onset of Puberty in Male Rats

“…Following the installation of the cannula, the minipump was implanted subcutaneously and all incisions were sealed with TissueTek (Websters Veterinary Supply, Milwaukee, Wisc., USA). The osmotic minipumps were precharged in physiologic saline and the PE tubing filled with the same solution as within the minipump – thus ensuring the immediate infusion of experimental solution or vehicle as described previously by our laboratory [16, 17]. Correct cannula placement was determined histologically at the end of the experiment.…”

“…Testicle weights were compared relative to total body weight. Minipump function was determined by the manufacturer’s suggestions and as reported previously by this laboratory [16, 17]. One half of animals were killed 7 days into treatment (PND31) and the remaining at the end of the treatment period (PND38) in order to determine if significant treatment effects began prior to preputial separation.…”

“…The minipump provided a constant flow of solution to the lateral ventricle 0.5 µl/h, 15 nmol/day of RFRP-3, NPFF or control for 14 days. This dose was determined as a high-end dose for ICV infusion in male rats compared to similar treatments for other neuropeptides published by our laboratory [16, 17]. Cannulas and minipumps were implanted on PND35 since male rats should normally enter puberty by PND42, well within the 14-day treatment period.…”

Galanin-like Peptide Ameliorates Obesity by Control of Food Intake and Energy Metabolism

“…In the 24 hours following the i.c.v. administration of 1.6 or 5 nmol GALP, body weight significantly decreased about 5 or 25 g compared with the vehicle treatment [38,40].…”

“…Increase of food intake (rat, short-term) Matsumoto et al [36] Lawrence et al [38] Lawrence et al [35] Kuramochi et al [37] Decrease of food intake (rat, long-term) Lawrence et al [38] Krasnow et al [41] Decrease of food intake and body weight (mouse) Hansen et al [43] Krasnow et al [41] Krasnow et al [32] Kauffman et al [42] Man et al [45] Increase in heat population Lawrence et al [38] Hansen et al [43] Man et al [45] Increase in oxygen consumption Rich et al [40] Enhancement of glucose and lipid metabolism Ito et al [46] …”