Cushing's Syndrome
K. Gupta, P. Carmichael, A. Zumla in 100 Short Cases for the MRCP, 2020
Nelson's syndrome formerly occurred as a complication of bilateral adrenalectomy for Cushing's disease. Over a 10-year period 10% to 20% of patients treated in this way will develop the syndrome. This is now less common due to the treatment of choice now being surgical resection of the pituitary adenoma by the trans-sphenoidal approach. The mechanism is very straightforward: in the absence of the negative feedback effect of cortisol, the ACTH secreting pituitary adenoma expands, causing headaches, visual problems and, if not treated, hypopituitarism. The characteristic increased pigmentation is secondary to a melanocyte stimulating component of the ACTH precursor molecule, pro-opiomelanocortin. In cases where an adenoma is not radiologically demonstrable, exploration of the pituitary fossa with or without venous sampling is carried out in those patients with a positive high dose dexamethasone suppression test. If no adenoma is found, a hypophysectomy is often performed. In those centres where bilateral adrenalectomy is performed in the absence of pituitary irradiation, then over a period of time a proportion may develop Nelson's syndrome.
Candidate Substances, Research Background, and Biological Roles
Shojiro Inoué in Biology of Sleep Substances, 2020
Jouvet5-7 proposed that sleep-inducing (hypnogenic) factors should take part in biochemical sequential chain reactions from A to B, from B to C, from C to …, leading to the final cause of sleep, whereas sleep-facilitating factors control the effector mechanisms of SWS and PS. On such a theoretical consideration he revised his classical monoamine theory166,167 to formulate the hydraulic theory of PS. In a similar fashion, Danguir168 suggested that digestive processes serially occurring after food intake finally result in sleep induction (ischymetric sleep theory; see Chapter 8). Cespuglio and colleagues169 and Chastrette et al.170 have focused their attention on the proopiomelanocortin family of peptides. A specific situation of waking state like that of stress induces the release of ACTH, which in turn produces desacetyl-α-melanocyte-stimulating hormone (a-MSH) and corticotropin-like intermediate lobe peptide (CLIP). ACTH, a-MSH, and CLIP can sequentially promote wakefulness, SWS, and PS, respectively (see also Chapter 8). In contrast, Drucker-Colín et al.171 postulated that many sleep factors can independently in parallel affect or impinge upon a mechanism which is the veritable element responsible for producing sleep.
Endocrine Functions of Brain Dopamine
Nira Ben-Jonathan in Dopamine, 2020
The main factors in the hypothalamic neurocircuitry associated with food intake are proopiomelanocortin (POMC) and its derivative alpha melanocyte stimulating hormone (αMSH) and cocaine- and amphetamine-related transcript (CART), NPY, agouti-related peptide (AgRP), orexins, melanin concentrating hormone (MCH), and the melanocortin receptors 3 and 4 (MCR 3&4). The major peripheral hormones associated with the regulation of body weight are adipose-derived leptin, pancreas-derived insulin and amylin, stomach-derived ghrelin, and intestinal-derived Cholecystokinin (CCK) and peptide tyrosine tyrosine (PYY). Few other factors, e.g., glucagon-like peptide 1 (GLP-1) and pancreatic polypeptide (PP), have also some contributions to the control of body weight but will not be covered here. Table 4.3 presents a list of major factors that regulate appetite and body weight.
COVID-19 and alcohol use disorder: putative differential gene expression patterns that might be associated with neurological complications
Published in Hospital Practice, 2022
Jibran Sualeh Muhammad, Ruqaiyyah Siddiqui, Naveed Ahmed Khan
Using the RNAseq expression databases previously mentioned, we co-plotted the expression profile of these genes in alcoholic versus normal and COVID-19 versus normal brain tissue. We observed that all the seven genes were upregulated significantly (p < 0.01) in both disease groups. Of note, three of these genes (VGF, NPTX2, and PDYN) depicted a twofold increase, and three genes (GHRL, IL1RL1, and RPRML) were overexpressed more than threefold in COVID-19 patients’ brain tissues compared to alcoholics’ brain tissues (Figure 2C). Next, protein–protein interaction analysis showed that the transcripts of three of these genes (GHRL, VGF, and PDYN) have several known or predicted interactions with Neuropeptide Y (NPY), Prepronociceptin protein (PNOC), Proopiomelanocortin (POMC), and several subtypes of Opioid Receptors (OPRM1, OPRL1, OPRK1, and OPRD1), suggesting a role in modulation of perception of pain. NPTX2 is shown to interact with PDYN, IL1RL1 has a predicted interaction with IL33, and VGF has known interactions with SCG3 (Figure 2D). Relevant functions of the seven candidate genes and eight genes of the closely interacting proteins are described (Table 1). Lastly, we elucidated the expression profile of these 15 genes in normal brain tissue. We found that VGF and SCG3 were upregulated in almost all types of human brain tissues, whereas the GHRL, IL1RL1, GHSR, and OPRM1 expression was very low (Figure 2E).
Olanzapine-samidorphan combination tablets for the treatment of schizophrenia and bipolar I disorder - what is it, and will it be used?
Published in Expert Review of Neurotherapeutics, 2022
Justin Faden, Ryan Serdenes, Leslie Citrome
Overall, several mechanisms explaining opioid mediated weight modulation have been proposed. Inhibition of hypothalamic proopiomelanocortin neuron-negative feedback via opioid receptor antagonists increase alpha-melanocyte-stimulating hormone and subsequent melanocortin-4 receptor mediated appetite suppression. Opioid receptor antagonism can also disinhibit GABAergic interneurons and inhibit glutamatergic input into ventral tegmental dopaminergic neurons projecting to the nucleus accumbens [44,45]. Finally, opioid receptor antagonism within the nucleus accumbens shell has been shown to reduce caloric intake [46]. Additional physiological relationships of cerebral opioids with orexin, ghrelin, leptin, and insulin have been identified and remain under investigation [47–50]. The mu-opioid receptor appears to be the most associated with obesity risk, via complex interplay via insulin, opioid and endocannabinoid messaging systems in the brain [51].
Possible roles of brain derived neurotrophic factor and corticotropin releasing hormone neurons in the nucleus of hippocampal commissure functioning within the avian neuroendocrine regulation of stress
Published in Stress, 2021
Hakeem J. Kadhim, Seong W. Kang, Wayne J. Kuenzel
Activation of parvocellular neurons within the avian hypothalamic paraventricular nucleus (PVN) resulted in an increase of corticotropin releasing hormone (CRH) and arginine vasotocin (AVT) (Kuenzel & Jurkevich, 2010). When CRH and AVT reach the anterior pituitary (APit), CRH binds to two G-protein coupled receptors, CRHR1 and CRHR2; AVT or AVP binds to the V1aR and V1bR. They, in turn, stimulate proopiomelanocortin (POMC) synthesis that is further processed to adrenocorticotropic hormone (ACTH) (Bonfiglio et al., 2011). In adrenal glands, ACTH activates the avian interrenal tissue to produce the stress hormone, corticosterone (CORT) (Herman et al., 2016; Romero, 2004). Stress hormone binds to glucocorticoid receptors (GRs) located on different tissues to provide energy for immediate use (McEwen, 2007) as well as to induce a negative feedback that regulates hypothalamic-pituitary-adrenocortical (HPA) axis activity (Keller-Wood, 2015; Chrousos, 2009; Vandenborne et al., 2005). Additionally, CRH neurons were identified in the nucleus of the hippocampal commissure (NHpC), an extra-hypothalamic structure, suggesting that the NHpC may be involved in the regulation of the stress response (Nagarajan et al., 2017a, 2014; Xie et al., 2010).
Related Knowledge Centers
- Anterior Pituitary
- Peptide
- Signal Peptide
- Vesicle
- Amino Acid
- Exocytosis
- Protein Biosynthesis
- Corticotropic Cell
- Translation
- Central Melanocortin System