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.
14617 Background: Prior studies associated statin use with prevention and reduced progression of prostate cancer. (Platz et al, 96th AACR abst. 4374). However, the effects of statins in hormone refractory prostate cancer (HRPC) are unknown. We evaluated the impact of statins on survival of HRPC patients by comparing actual survival data with predicted survival using the Halabi nomogram (JCO 21:(7);1232). Methods: Using the Iowa City VA (ICVA) prescription database since 2001 along with chart review, we identified 28 consecutive patients who were prescribed statins when they had HRPC. Survival information, duration of statin use while HRPC, and Halabi nomogram variables were collected (Hb, PS, Alk Phos, Gleason, PSA). An LDH value of 90 U/L (low-normal at ICVA) was used for all patients, since LDH values were not available. Log-rank and and Cox regression analyses were performed. The outcome of interest was overall survival. Patients alive at last follow-up were censored. Statin use was treated as a time-dependent covariate in the regression analysis, and subject-specific predicted survival from the Halabi nomogram as another covariate. Results: 17 patients were alive and 11 had died. Median duration of follow-up for patients alive was 23 months. The observed vs. nomogram-predicted estimated median survivals were 36 vs. 17 months, respectively. Study patients significantly outlived their nomogram-predicted survival (p = 0.0004). Four patients had negative bone scans. 12 patients outlived their nomogram, 8 died before, and 8 were indeterminate (censored prior to their Halabi-predicted survival). Risk of death decreased with greater length of statin use (p = 0.02). When covariates for Halabi nomogram and statin use were both included in a multivariate regression model, neither was statistically significant, although similar point estimates for the relative risks were obtained. Conclusions: Statin use, and longer duration of use, significantly improved survival of HRPC patients in univariate analysis. The sample size limits the multivariate analysis. Evaluation of a time-dependent statin effect in HRPC could be considered in larger studies. No significant financial relationships to disclose.
Previous work has shown that the neurosteroid progesterone (PROG) and hypothalamic hormone thyrotropin releasing hormone (TRH) improve molecular and functional outcomes following traumatic brain injury (TBI) when used independently. This work was designed to evaluate if a combination of PROG and TRH results in further improvements in outcomes. Adult male Sprague‐Dawley rats were given a medial frontal cortex contusion using a weight‐drop device after craniotomy. After TBI, rats were treated with PROG (5 d), TRH (1 injection at 1 h post‐injury), or the combination of the two drugs (PROG+TRH). Uninjured sham‐operated and vehicle‐treated TBI rats served as controls. PROG+TRH treatment resulted in significant improvements in both sensory skills and learning and memory as measured by the tactile adhesive test and Morris Water Maze, respectively (n=11/group). Analysis of putative mechanisms responsible for these behavioral observations suggest that the tumor suppressor protein p53, the inflammatory marker TNF‐α, and GFAP‐positive reactive gliosis may all participate in the efficacy of this combinatorial treatment. Furthermore, preliminary use of diffusion magnetic resonance imaging at 21 Tesla (21T) suggests that diffusion MRI is a valuable novel tool in future determination of mechanisms and the ways to reduce water accumulation and edema after treatment.
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