Endocrine Abstracts

Low-carbohydrate/high fat diets (LC-HFD) effectively induce body weight loss in both animals and humans; however, in rats this is paralleled by increased visceral adiposity contributing to impaired glucose tolerance. Estrogen inhibits adipose tissue accumulation, with estrogen deficient female animals displaying increased body weight and visceral adiposity with reduced insulin sensitivity, which can be reversed with estrogen replacement. Consistent with the effects seen in fem...

Small cell lung cancer (SCLC) is highly aggressive with a particularly poor prognosis. This is due to tumours quickly metastasising and developing chemoresistance. SCLC tumours possess neuroendocrine properties in that they secrete prohormones such as pro-opiomelanocortin (POMC) and pro-gastrin releasing peptide (pro-GRP). These can be detected in the circulation and therefore have potential as biomarkers for prognosis and relapse. The aims of this study are; i) develop a mode...

Animals that are not exposed to endogenous sex steroids during development provide an important model for studying hormone independent development of brain sex differences. Due to gonadal agenesis, male and female steroidogenic factor 1 knockout (SF-1 KO) mice are born phenotypically female. Normally, they die shortly after birth due to adrenal insufficiency. Early corticosteroid injections followed by adrenal transplantation can maintain SF-1 KO mice into adulthood. As severa...

Previous studies investigating steroidogenic enzymes in the brain have often focused on only a few genes at a time, using animal models or pooled human RNA to investigate their expression. For this study, we obtained RNA from individual archived human brain tissue samples in order to analyse the transcription of twelve genes involved with steroid biosynthesis and metabolism within the cerebellum and hippocampus.We developed realtime RT-PCR assays for twe...

Various psychiatric conditions have been associated with stress and alterations in hypothalamic-pituitary-adrenal (HPA) activity. Yet while stress is a general phenomenon, illness is only seen in a proportion of individuals, suggesting genetic modifiers of ability to cope with stress. 11-beta hydroxysteroid dehydrogenase type 1 (HSD1) regenerates corticosterone from inert 11-dehydrocorticosterone, amplifying the levels of glucocorticoids and is expressed in the brain. To deter...

NPY acts centrally to stimulate appetite and the HPA axis. During late pregnancy enhanced inhibition of parvocellular paraventricular nucleus (pPVN) corticotrophin releasing hormone (CRH)/ arginine vasopressin (AVP) neurones reduces HPA-axis stress responses1,2. We investigated activation of hypothalamic neurones regulating HPA responses to NPY, and a role for endogenous opioids in HPA hyporesponsiveness in late pregnancy.Pregnant (d21) and vi...

Decades of clinical experience and research in human and non-human primates demonstrate that maternal care received early in life strongly influences the development of parenting and other social skills as well as resiliency in the face of stress. Analogous intergenerational effects of maternal nurturing have recently been reported in rats. Adult stress responses (anxiety and hypothalamic-pituitary-adrenal axis activation) are inversely related to the amount of maternal lickin...

Gene delivery to the CNS is undermined by the lack of suitable vectors capable of delivering genes with sufficient specificity, efficacy and safety. In previous studies we have shown that bacteriophage particles, which lack tropism for mammalian cells, can be genetically modified to display specific ligands that allow binding, internalisation and cell transduction of receptor-bearing target cells. Moreover, phage particles can be forced to evolve using combinatorial techniques...

Gene delivery to the CNS is undermined by the lack of suitable vectors capable of delivering genes with sufficient specificity, efficacy and safety. In previous studies we have shown that bacteriophage particles, which lack tropism for mammalian cells, can be genetically modified to display specific ligands that allow binding, internalisation and cell transduction of receptor-bearing target cells. Moreover, phage particles can be forced to evolve using combinatorial techniques...

In late pregnancy, the hypothalamo-pituitary-adrenal (HPA) axis is less responsive to immune challenge(1). Circulating and brain levels of allopregnanolone (AP), a neuroactive steroid and allosteric enhancer at inhibitory GABAA receptors, increase during pregnancy(2) and AP treatment attenuates stress-induced HPA activity in male rats(3). Here we sought a role for AP in attenuated HPA axis responses to interleukin-1-beta (IL-1B) in pregnant rats. Conscious pregnant (day 21) an...