In the years 1947–57, following a turbulent retirement, Ugo Cerletti, the father of electroconvulsive therapy (ECT) (1938), invested his energies in a new audacious project conceived as an extension of his ECT research. Forced to leave the direction of the Sapienza University Clinic, he got funds from the National Research Council of Italy to carry out his experimental activities, and founded a ‘Center for the study of the physiopathology of Electro-shock’ in Rome. The Center was aimed at studying liquid substances extracted from electro-shocked animals’ brains that Cerletti named acroagonine and injected into human patients. Inspired by coeval literature, Cerletti believed that electroshock efficacy was due to stimulating some homeostatic processes in the brain, specifically in the meso-diencephalic area (i.e. involving neuroendocrine response in the hypothalamic–pituitary–adrenal axis). Cerletti’s team wished not only to find these effects, but also to reproduce them. With this hypothesis, that proved ineffective, Cerletti anticipated intuitions on the neuroendocrine effects of ECT and the necessity for the development of psychopharmacology. In this article, I cross-combined previously unexplored archival materials stored at Sapienza University of Rome (‘ES Section’) with established bibliographic and archival sources.

Person-centered methods represent an important advance in the simultaneous examination of multiple indicators of neuroendocrine functioning and may facilitate a more nuanced understanding of the impact of child maltreatment on hypothalamic–pituitary–adrenal axis dysregulation. The aims of the present study were threefold: (a) identify naturally occurring patterns of diurnal cortisol and dehydroepiandrosterone (DHEA) regulation among a sample of N = 1,258 children with and without histories of maltreatment, (b) investigate which neuroendocrine profiles characterize children with exposure to maltreatment, and (c) examine which profiles are related to adaptive outcomes and symptomatology among children. Cortisol and DHEA were sampled three times per day (9 a.m., 12 p.m., and 4 p.m.) across 5 and 2 days, respectively. Four profiles of cortisol and DHEA regulation were identified. Among females, a pattern marked by high cortisol and low DHEA was associated with more pervasive maltreatment experiences. Furthermore, we found evidence of adaptive interpersonal resilience such that children with maltreatment exposure who evidenced this pattern of high cortisol and low DHEA were viewed as more likeable than maltreated children with other neuroendocrine patterns. Finally, results pointed to higher levels of internalizing symptoms among children who displayed a profile marked by average cortisol and high DHEA.

The thymus undergoes a critical period of growth and development early in gestation and, by mid-gestation, immature thymocytes are subject to positive and negative selection. Exposure to undernutrition during these periods may permanently affect phenotype. We measured thymulin concentrations, as a proxy for thymic size and function, in children (n = 290; aged 9–13 years) born to participants in a cluster-randomized trial of maternal vitamin A or β-carotene supplementation in rural Nepal (1994–1997). The geometric mean (95% confidence interval) thymulin concentration was 1.37 ng/ml (1.27, 1.47). A multivariate model of early-life exposures revealed a positive association with gestational age at delivery (β = 0.02; P = 0.05) and higher concentrations among children born to β-carotene-supplemented mothers (β = 0.19; P < 0.05). At ∼9–12 years of age, thymulin was positively associated with all anthropometric measures, with height retained in our multivariate model (β = 0.02; P < 0.001). There was significant seasonal variation: concentrations tended to be lower pre-monsoon (β = −0.13; P = 0.15), during the monsoon (β = −0.22; P = 0.04), and pre-harvest (β = −0.34; P = 0.01), relative to the post-harvest season. All early-life associations, except supplementation, were mediated in part by nutritional status at follow-up. Our findings underscore the known sensitivity of the thymus to nutrition, including potentially lasting effects of early nutritional exposures. The relevance of these findings to later disease risk remains to be explored, particularly given the role of thymulin in the neuroendocrine regulation of inflammation.

The advent of genomic selection has led to increased interest within the cattle breeding industry to market semen from young bulls as early as possible. However, both the quantity and quality of such semen is dictated by the age at which these animals reach puberty. Enhancing early life plane of nutrition of the bull stimulates a complex biochemical interplay involving metabolic and neuroendocrine signalling and culminating in enhanced testicular growth and development and earlier onset of sexual maturation. Recent evidence suggests that an enhanced plane of nutrition leads to an advancement of testicular development in bulls at 18 weeks of age. However, as of yet, much of the neuronal mechanisms regulating these developmental processes remain to be elucidated in the bull. While early life nutrition clearly affects the sexual maturation process in bulls, there is little evidence for latent effects on semen traits post-puberty. Equally the influence of prevailing nutritional status on the fertility of mature bulls is unclear though management practices that result in clinical or even subclinical metabolic disease can undoubtedly impact upon normal sexual function. Dietary supplements enriched with various polyunsaturated fatty acids or fortified with trace elements do not consistently affect reproductive function in the bull, certainly where animals are already adequately nourished. Further insight on how nutrition mediates the biochemical interaction between neuroendocrine and testicular processes will facilitate optimisation of nutritional regimens to optimise sexual maturation and subsequent semen production in bulls.

The acquisition of neuroendocrine (NE) characteristics by prostate cancer (PC) cells relates to tumor progression and hormone resistance. PC cells may survive and function in androgen-deprived environments, where they could establish paracrine signaling networks, providing stimuli for the propagation of local carcinoma cells. We previously demonstrated, using electron probe X-ray microanalysis (EPXMA), in LNCaP, PC-3, and Du 145 cell lines that apoptosis is associated with intracellular elemental changes, and that the NE secretory products, bombesin and calcitonin, inhibit etoposide-induced apoptosis, as well as some of these elemental changes. In this study, LNCaP cells were induced in vitro to transdifferentiate under androgen deprivation, to mimic the role of NE cells in the apoptotic activity of transdifferentiated androgen-dependent PC cells. Changes in intracellular ion content associated with apoptosis, assessed by EPXMA, demonstrate that the transdifferentiated LNCaP cells are resistant to etoposide-induced apoptosis and also to the etoposide-induced elemental changes. The aggressive malignant potential of PC with neuroendocrine differentiation, associated with hormonal independence, is partly because of the ability that most NE tumor cells have to escape apoptosis, which can enhance the malignant properties of tumor cells and may have therapeutic implications as tumor cells are usually resistant to cytotoxic drugs as etoposide.

Fatigue is a common problem; when chronic and disabling, subjects can be categorized as having chronic fatigue syndrome (CFS). Whilst it is most likely a multifactorial condition of biopsychosocial origin, the nature of the pathophysiological component remains unclear. There has been a wealth of interest in the possible hypothalamo–pituitary–adrenal (HPA) axis dysfunction in CFS, and whether such changes may mediate fatigue. On balance, there appears to be reduced cortisol output in a proportion of patients, together with heightened negative feedback and glucocorticoid receptor function. There is evidence for impaired adrenocorticotropic hormone (ACTH) and cortisol responses to a variety of challenges. However, there is no evidence for a specific or uniform dysfunction of the HPA axis. Evidence that these changes may be related to symptom production comes from randomized controlled trials of glucocorticoid replacement therapy, which have shown improvements in fatigue and disability. Given the many factors that may impinge on the HPA axis in CFS, such as inactivity, sleep disturbance, psychiatric comorbidity, medication and ongoing stress, it seems likely that there is not a single or specific change to the HPA axis in CFS and that the observed HPA axis disturbances are of multifactorial etiology. This is further supported by a comparison of neuroendocrine findings in other conditions in which fatigue is prominent, showing both similarities and differences with the pattern in CFS.

Epithelial cells lining the inner surface of the intestinal epithelium are in direct contact with a lumenal environment that varies dramatically with diet. It has long been suggested that the intestinal epithelium can sense the nutrient composition of lumenal contents. It is only recently that the nature of intestinal nutrient-sensing molecules and underlying mechanisms have been elucidated. There are a number of nutrient sensors expressed on the luminal membrane of endocrine cells that are activated by various dietary nutrients. We showed that the intestinal glucose sensor, T1R2+T1R3 and the G-protein, gustducin are expressed in endocrine cells. Eliminating sweet transduction in mice in vivo by deletion of either gustducin or T1R3 prevented dietary monosaccharide- and artificial sweetener-induced up-regulation of the Na+/glucose cotransporter, SGLT1 observed in wild-type mice. Transgenic mice, lacking gustducin or T1R3 had deficiencies in secretion of glucagon-like peptide 1 (GLP-1) and, glucose-dependent insulinotrophic peptide (GIP). Furthermore, they had an abnormal insulin profile and prolonged elevation of postprandial blood glucose in response to orally ingested carbohydrates. GIP and GLP-1 increase insulin secretion, while glucagon-like peptide 2 (GLP-2) modulates intestinal growth, blood flow and expression of SGLT1. The receptor for GLP-2 resides in enteric neurons and not in any surface epithelial cells, suggesting the involvement of the enteric nervous system in SGLT1 up-regulation. The accessibility of the glucose sensor and the important role that it plays in regulation of intestinal glucose absorption and glucose homeostasis makes it an attractive nutritional and therapeutic target for manipulation.

With the exception of moderately differentiated neuroendocrine carcinoma of the larynx, neuroendocrine carcinomas are very rare head and neck malignancies. We report a case of a small cell neuroendocrine carcinoma in the petrous apex of the temporal bone. This unusual site for this tumour has not yet been reported in the literature. We confirmed the location and extent of the primary tumour by positron-emission tomography scan. The final histopathological diagnosis was of small cell carcinoma, and this was confirmed by immunohistochemistry. We treated this patient with surgery followed by radiotherapy and chemotherapy. After the treatment was completed there was subtotal remission of the tumour, with no distant metastases.

The clinical and histopathological characteristics of seven cases of Moderately Differentiated Neuroendocrine Carcinomas (MDNEC) and two cases of Poorly Differentiated Neuroendocrine Carcinomas (PDNEC) have been reviewed. The tumours arose in the supraglottis of predominantly elderly men. Two cases had raised levels of urinary 5-hydroxy-indole-acetic acid at presentation but no case developed the carcinoid syndrome. PDNEC were histologically identical to the oat cell type carcinoma of the bronchus and were associated with an extremely aggressive clinical course with both patients dying of widespread metastases within one month of registration. MDNEC also metastasized frequently with four of seven cases dying with widespread disease. The tumours have previously been reported as not being radiosensitive; however three cases remain free of disease following biopsy and radiotherapy alone. The place of radiotherapy in the management of these tumours is discussed.

Although mating is a necessary prerequisite for the induction of ovulation in the tsetse fly, Glossina morsitans morsitans, neither the accessory gland substance from the male nor any testicular component is responsible for causing ovulation. Experimental evidence suggest that two neural factors, one originating from the uterus during mating act as an afferent stimulus, and the other originating from the ovary during oocyte maturation regulate a cerebral hormonal factor which controls the event of ovulation. It is probable that one successful copulation removes an inhibition for the release of an ovulation stimulating hormone from the neurohemal organ into the circulation. The rate of synthesis and/or transport of the hormone from the neurosecretory cells to the neurohemal organ is probably regulated by the rate of oocyte development.