Journal of Endocrinology 

About: Journal of Endocrinology is an academic journal published by Bioscientifica. The journal publishes majorly in the area(s): Prolactin & Insulin. It has an ISSN identifier of 0022-0795. Over the lifetime, 15099 publications have been published receiving 502839 citations.

The role of corticotropin-releasing factor in depression and anxiety disorders

Abstract: Corticotropin-releasing factor (CRF), a 41 amino acid-containing peptide, appears to mediate not only the endocrine but also the autonomic and behavioral responses to stress. Stress, in particular early-life stress such as childhood abuse and neglect, has been associated with a higher prevalence rate of affective and anxiety disorders in adulthood. In the present review, we describe the evidence suggesting that CRF is hypersecreted from hypothalamic as well as from extrahypothalamic neurons in depression, resulting in hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and elevations of cerebrospinal fluid (CSF) concentrations of CRF. This increase in CRF neuronal activity is also believed to mediate certain of the behavioral symptoms of depression involving sleep and appetite disturbances, reduced libido, and psychomotor changes. The hyperactivity of CRF neuronal systems appears to be a state marker for depression because HPA axis hyperactivity normalizes following successful antidepressant treatment. Similar biochemical and behavioral findings have been observed in adult rats and monkeys that have been subjected to early-life stress. In contrast, clinical studies have not revealed any consistent changes in CSF CRF concentrations in patients with anxiety disorders; however, preclinical findings strongly implicate a role for CRF in the pathophysiology of certain anxiety disorders, probably through its effects on central noradrenergic systems. The findings reviewed here support the hypothesis that CRF receptor antagonists may represent a novel class of antidepressants and/or anxiolytics.

Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor

Abstract: Extracellular matrices (ECM) are secreted molecules that constitute the cell microenvironment, composed of a dynamic and complex array of glycoproteins, collagens, glycosaminoglycans and proteoglycans. ECM provides the bulk, shape and strength of many tissues in vivo, such as basement membrane, bone and cartilage. In vitro, most animal cells can only grow when they are attached to surfaces through ECM. ECM is also the substrate for cell migration. However, ECM provides much more than just mechanical and structural support, with implications in developmental patterning, stem cell niches and cancer. ECM imparts spatial context for signalling events by various cell surface growth factor receptors and adhesion molecules such as integrins. The external physical properties of ECM may also have a role in the signalling process. ECM molecules can be flexible and extendable, and mechanical tension can expose cryptic sites, which could further interact with growth factors or their receptors. ECM proteins and structures can determine the cell behaviour, polarity, migration, differentiation, proliferation and survival by communicating with the intracellular cytoskeleton and transmission of growth factor signals. Integrins and proteoglycans are the major ECM adhesion receptors which cooperate in signalling events, determining the signalling outcomes, and thus the cell fate. This review focuses on the emerging concept of spatial cell biology of ECM, especially the current understanding of integrins and heparan sulphate proteoglycans as the essential cellular machineries that sense, integrate and respond to the physical and chemical environmental information either by directly connecting with the local adhesion sites or by regulating global cellular processes through growth factor receptor signalling pathways, leading to the integration of both external and internal signals in space and time.

Several environmental oestrogens are also anti-androgens

Abstract: There is presently considerable interest in endocrine disruption which is a new area of endocrinology concerned with chemicals that mimic hormones, in particular sex steroids. It has been hypothesised that exposure to such chemicals may be responsible for adverse effects in both humans and wildlife. Until now, chemicals that mimic oestrogens (so-called xenoestrogens) have been the main focus of endocrine disruption research. However, recent evidence suggests that many abnormalities in the male reproductive system may be mediated via the androgen receptor. By blocking androgen action, exposure to an anti-androgen may cause changes similar to those associated with oestrogen exposure. We have used in vitro yeast-based assays to detect oestrogenic, anti-oestrogenic, androgenic and anti-androgenic activities in a variety of chemicals of current interest. We show that many of the so-called 'environmental oestrogens' also possess anti-androgenic activity. The previously reported anti-androgenic activities of vinclozolin and p,p'-1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) were confirmed. We also found that o,p'-1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), bisphenol A and butyl benzyl phthalate were anti-androgenic. However, not all xenoestrogens are also anti-androgenic, because nonylphenol was found to be a weak androgen agonist. Our results demonstrate that hormone-mimicking chemicals can have multiple hormonal activities, which may make it difficult to interpret their mechanisms of action in vivo. Although not a specific objective of this study, our results also demonstrate that yeast-based assays are powerful tools with which to investigate both agonist and antagonistic hormonal activities of chemicals.

Premature delivery of foetal lambs infused with glucocorticoids.

Abstract: Dexamethasone caused premature delivery when infused into foetal lambs at rates of 0\m=.\06-4\m=.\0mg./24 hr. but it had no effect when administered to pregnant ewes at the rate of 4\m=.\0mg./24 hr. Infusions into the foetus of deoxycorticosterone or corticosterone were ineffective; mixtures of dexamethasone and deoxycorticosterone did not cause parturition more rapidly than dexamethasone alone. Thus, the ability of corticosteroids to cause premature parturition appears to depend on glucocorticoid rather than mineralocorticoid activity. Parturition induced by dexamethasone was not delayed by administration of 100 mg. progesterone/24 hr. to the ewe or to the foetus. This suggests either that withdrawal of inhibitory effects of progesterone on the myometrium can occur independently of the progesterone concentration in peripheral plasma, or that the mechanism of parturition provoked by corticosteroids in the foetus can override any regulatory influence of progesterone

Peroxisome proliferator-activated receptors in inflammation control.

Abstract: Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily. PPARalpha is highly expressed in liver, skeletal muscle, kidney, heart and the vascular wall. PPARgamma is predominantly detected in adipose tissue, intestine and macrophages. PPARs are activated by fatty-acid derivatives and pharmacological agents such as fibrates and glitazones which are specific for PPARalpha and PPARgamma respectively. PPARs regulate lipid and lipoprotein metabolism, glucose homeostasis, cell proliferation and differentiation, and apoptosis. PPARalpha controls intra- and extracellular lipid metabolisms whereas PPARgamma triggers adipocyte differentiation and promotes lipid storage. In addition, PPARs also modulate the inflammatory response. PPAR activators have been shown to exert anti-inflammatory activities in various cell types by inhibiting the expression of proinflammatory genes such as cytokines, metalloproteases and acute-phase proteins. PPARs negatively regulate the transcription of inflammatory response genes by antagonizing the AP-1, nuclear factor-kappaB (NF-kappaB), signal transducer and activator of transcription and nuclear factor of activated T-cells signalling pathways and by stimulating the catabolism of proinflammatory eicosanoids. These recent findings indicate a modulatory role for PPARs in inflammation with potential therapeutical applications in chronic inflammatory diseases.