ABSTRACT
BACKGROUND: Early and accurate prediction of outcome in acute stroke is important and influences risk-optimized therapeutic strategies. Endocrine alterations of the hypothalamic-pituitary axis are amongst the first measurable alterations after cerebral ischaemia. We therefore evaluated the prognostic value of cortisol, triiodothyronine (T3), free thyroxine (fT4), thyroid-stimulating hormone (TSH) and growth hormone (GH) in patients with an acute ischaemic stroke. METHODS: In an observational study including 281 patients with ischaemic stroke, anterior pituitary axis hormones (i.e. cortisol, T3, fT4, TSH and GH) were simultaneously assessed to determine their value to predict functional outcome and mortality within 90 days and 1 year. RESULTS: In receiver operating characteristic curve analysis, the prognostic accuracy of cortisol was higher compared to all measured hormones and was in the range of the National Institutes of Health Stroke Scale (NIHSS). Cortisol was an independent prognostic marker of functional outcome and death [odds ratio (OR) 1.0 (1.0-1.01) and 1.62 (1.37-1.92), respectively, P<0.0002 for both, adjusted for age and the NIHSS] in patients with ischaemic stroke, but added no significant additional predictive value to the clinical NIHSS score. CONCLUSION: Cortisol is an independent prognostic marker for death and functional outcome within 90 days and 1 year in patients with ischaemic stroke. By contrast, other anterior pituitary axis hormones such as peripheral thyroid hormones and GH are only of minor value to predict outcome in stroke.
Subject(s)
Brain Ischemia/blood , Pituitary Hormones, Anterior/blood , Stroke/blood , Aged , Aged, 80 and over , Biomarkers/blood , Brain Ischemia/complications , Epidemiologic Methods , Female , Human Growth Hormone/blood , Humans , Hydrocortisone/blood , Male , Middle Aged , Prognosis , Stroke/etiology , Thyrotropin/blood , Thyroxine/blood , Triiodothyronine/bloodABSTRACT
The expression of prepro-orexin (PPO) mRNA in the rat brain was investigated by in situ hybridization histochemistry. In the lateral and posterior hypothalamic areas, which are considered to produce exclusively PPO mRNA, we found high levels of PPO mRNA expressions. We also localized PPO mRNA hybridization signals at lower levels around the lateral ventricles, the third and fourth ventricle. Cellular analysis by emulsion autoradiography revealed the expression of PPO mRNA in the ependymal cell layer. Our results demonstrate that beside the lateral and posterior hypothalamus PPO mRNA is expressed in ependymal cells.
Subject(s)
Ependyma/cytology , Ependyma/metabolism , Gene Expression Regulation/physiology , Neuropeptides/biosynthesis , Neuropeptides/genetics , Protein Precursors/biosynthesis , Protein Precursors/genetics , Animals , Fourth Ventricle/cytology , Fourth Ventricle/metabolism , Hypothalamic Area, Lateral/cytology , Hypothalamic Area, Lateral/metabolism , Intracellular Signaling Peptides and Proteins , Lateral Ventricles/cytology , Lateral Ventricles/metabolism , Male , Molecular Sequence Data , Orexins , RNA, Messenger/metabolism , Rats , Rats, Wistar , Third Ventricle/cytology , Third Ventricle/metabolismABSTRACT
Orexins are produced specifically by neurons located in the lateral hypothalamus. Recent results suggested peripheral actions of orexins. Therefore, we analyzed the mRNA expression of prepro-orexin and the orexin receptor subtypes OX(1) and OX(2) in peripheral rat tissues. Using real-time quantitative RT-PCR we detected significant amounts of prepro-orexin mRNA in testis, but not in ovaries. OX(1) receptor mRNA was highly expressed in the brain and at lower levels in the pituitary gland. Only small amounts of OX(1) receptor mRNA were found in other tissues such as kidney, adrenal, thyroid, testis, ovaries, and jejunum. Very high levels of OX(2) receptor mRNA, 4-fold higher than in brain, were found in adrenal glands of male rats. Low amounts of OX(2) receptor mRNA were present in lung and pituitary. In adrenal glands, OX(2) receptor mRNA was localized in the zona glomerulosa and reticularis by in situ hybridization, indicating a role in adrenal steroid synthesis and/or release. OX(1) receptor mRNA in the pituitary and OX(2) receptor mRNA in the adrenal gland were much higher in male than in female rats. In the hypothalamus, OX(1) receptor mRNA was slightly elevated in female rats. The differential mRNA expression of orexin receptor subtypes in peripheral organs indicates discrete peripheral effects of orexins and the existence of a peripheral orexin system. This is supported by the detection of orexin A in rat plasma. Moreover, the sexually dimorphic expression of OX(1) and OX(2) receptors in the hypothalamus, pituitary, and adrenal glands suggests gender-specific roles of orexins in the control of endocrine functions.
