Although numerous data showing severe morphological impairment of magnocellular and parvocellular hypothalamic neurons due to chronic alcoholic consumption have been gathered from animal experiments, only one study (Harding et al., 1996) was performed on POST MORTEM human brain. This study showed a reduction in the number of vasopressin (VP)-immunoreactive neurons in the supraoptic (SON) and paraventricular (PVN) nuclei, but did not provide any data regarding the effect of chronic alcohol intake on human parvocellular neurons. In order to assess whether the changes observed in the animal model also occur in humans and provide a structural basis for the results of clinical tests, we performed immunohistochemical and morphometric analysis of magnocellular (VP and oxytocin, OT) and parvocellular (corticotropin-releasing hormone, CRH) neurons in post-mortem brains of patients afflicted with chronic alcoholic disease. We analyzed 26-male alcoholics and 22 age-matched controls divided into two age groups--"young" (< 40 yr) and "old" (> 40 yr). Hypothalamic sections were stained for OT, VP, and CRH. The analysis revealed: 1) decrease in VP-immunoreactivity in the SON and PVN as well as OT-immunoreactivity in the SON in alcoholic patients; 2) increase in OT-immunoreactivity in the PVN; 3) increase in CRH-immunoreactivity in parvocellular neurons in the PVN. Furthermore, the proportion of cells containing CRH and VP was increased in alcoholics. These findings indicate that chronic alcohol consumption does indeed impair the morphology of magnocellular neurons. The enhancement of CRH-immunoreactivity and increased co-production of CRH and VP in parvocellular neurons may be due to a decline in glucocorticoid production, implied by the hypoplasic impairment of adrenal cortex we observed in alcoholics during the course of this study.

Neuroendocrine factors play an important role in the pathogenesis of chronic heart failure. Despite numerous clinical and experimental studies, the role of the hypothalamic-pituitary-adrenal axis and glucocorticoid hormones is not fully characterised. Here we present a study of plasma cortisol concentration in 74 chronic heart failure patients, divided into four groups based on NYHA functional classes I-IV, and in 17 control subjects. In parallel, we performed morphological analysis of the hypothalamic-pituitary-adrenal axis components from 8 male patients who had died from chronic heart failure, and 9 male controls. In our study we applied immunohistochemical method and quantitative analysis to investigate an expression of hypothalamic neurohormones (corticotropin-releasing hormone, vasopressin) and adrenocorticotropin hormone in the pituitary, as well as performed general histological examination of the adrenal cortex. Measurement of morning cortisol concentration in plasma of chronic heart failure patients revealed neither difference compared to controls nor with the severity of the disease. Despite this, a two-fold increase in the density of corticotropin-releasing hormone-immunoreactive neurons as well as a two-fold increase in the number of corticotropin-releasing hormone neurons co-expressing vasopressin in the hypothalamic paraventricular nucleus were found. In the anterior pituitary the density of adrenocorticotropin hormone-immunoreactive cells was significantly increased. General histological analysis of the adrenal cortex revealed a drastic thinning of the zona fasciculata and dystrophic changes in corticocytes. Structural changes, observed in the adrenal cortex, suggest a relative glucocorticoid deficiency, which may contribute to corticotropin-releasing hormone and adrenocorticotropin hormone upregulation in hypothalamus and pituitary of chronic heart failure patients.

The hypothalamic nonapeptide vasopressin is a known player in the pathogenesis of chronic heart failure. According to the large body of clinical evidence, vasopressin has an impact on salt and water imbalance, hyponatremia, and subsequent renal insufficiency - the most common and destructive co-morbidity of patients afflicted with chronic heart failure. Despite the well-documented elevated levels of vasopressin in the blood of such patients, its expression in the magnocellular hypothalamic nuclei and transport to the posterior pituitary has not yet been investigated. In addition, the literature almost lacks the information on the contribution of another member of nonapeptide family, oxytocin, in the pathogenesis of this disease. Here we present a postmortem analysis of vasopressin and oxytocin-immunoreactive neurons and their terminals in the posterior pituitary of 8 male patients (53.8+/-9.3 years) who had died from CHF and 9 male controls (54.6+/-11.8 years). In line with previous clinical reports, our study on hypothalami of chronic heart failure patients revealed a significant increase in the relative profile density (+29%) of vasopressin-positive neurons in the hypothalamic supraoptic nucleus. Consistently we found a significant increase in the relative optic density of vasopressin-immunoreactivity in the posterior pituitary (+33%) of these patients. In contrast, the similar analysis applied for oxytocin neurons revealed no statistically significant differences to controls. In conclusion, our study provides the morphological evidence for activation of vasopressin (but not oxytocin) expression and vasopressin transport to the posterior pituitary in patients with chronic heart failure.