A direct androgenic involvement in the expression of human corticotropin-releasing hormone

Am, Bao; Fischer, David F.; Yh, Wu; Hol, Elly M.; Balesar, Rawien; Ua, Unmehopa; Zhou, Jiang‐Ning; Swaab, Dick F.

doi:10.1038/sj.mp.4001800

Cited by 105 publications

(74 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…28,67 In contrast to estrogens, androgens may inhibit CRF gene expression via AR expressed by CRF neurons, acting by androgen-responsive elements in the CRF-promoter region. 29,68 In the present study, we found a differential change in sex hormone receptors. The expression of ESR1 mRNA was upregu-lated in depressed subjects, whereas AR was downregulated compared with the controls.…”

Section: Sex Hormones Receptor Imbalancesupporting

confidence: 55%

“…64 Sex hormones can affect the HPA axis in a direct way via ESRs and ARs that are expressed by CRF neurons. 28,29 There are five perfect half-palindromic estrogenresponsive elements in the human CRF-promoter region, which may confer direct estrogenic stimulation on CRF gene expression. 28,65 Differential effects have been described in vitro on gene expression by the two receptor subtypes ESR1 and 2.…”

Section: Sex Hormones Receptor Imbalancementioning

confidence: 99%

“…MR and GR can form hetero-and homodimers that differ in their activity of gene regulation. A change in the balance of MR/GR ratio in depressed patients may contribute to the change in transcription rate of CRF [16][17][18][19][20] ; (2) the CRF receptors, that is, CRFR1 that stimulates CRF production 21,22 and CRFR2 that opposes this action 23 ; (3) alterations in vasopressinergic systems that potentiate effects of CRF 24 and the AVP receptor 1a (AVPR1A) that is involved in anxiety/ depressionrelated behavior 25 ; oxytocin (OXT) that attenuates the stress response was found to be increased in the PVN only in melancholic depression 26 ; (4) cAMP-response element-binding protein (CREB) that stimulates CRF expression as a transcription factor 27 ; (5) sex hormones, involving estrogen-receptors (ESR) 1 and 2 and androgen-receptor (AR), stimulating and inhibiting CRF gene expression, respectively 28,29 ; (6) the powerful CRF-stimulating proinflammatory cytokines such as interleukin 1-b (IL1b) that is produced by glial cells and PVN neurons, 30 and tumor necrosis factor-a (TNFa), a circulating state marker for depression 31 that is also produced by glial cells 32 ;…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

et al. 2008

Self Cite

View full text Add to dashboard Cite

Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors that stimulate or inhibit CRF expression, including (1) corticosteroid receptors and their chaperones, heat shock proteins 70 and 90, (2) sex hormone receptors, (3) CRF receptors 1 (CRFR1) and 2, (4) cytokines interleukin 1-b and tumor necrosis factor-a, (5) neuropeptides and receptors, vasopressin (AVP), AVP receptor 1a (AVPR1A) and oxytocin and (6) transcription factor cAMP-response element-binding protein. We hypothesized that, in depression, the transcript levels of those genes that are involved in the activation of the hypothalamo-pituitary-adrenal (HPA) axis are upregulated, whereas the transcript levels of the genes involved in the inhibition of the HPA axis are downregulated. We performed laser microdissection and real-time PCR in the PVN and as a control in the supraoptic nucleus. Snap-frozen post-mortem hypothalami of seven depressed and seven matched controls were used. We found significantly increased CRF mRNA levels in the PVN of the depressed patients. This was accompanied by a significantly increased expression of four genes that are involved in the activation of CRF neurons, that is, CRFR1, estrogen receptor-a, AVPR1A and mineralocorticoid receptor, while the expression of the androgen receptor mRNA involved in the inhibition of CRF neurons was decreased significantly. These findings raise the possibility that a disturbed balance in the production of receptors may contribute to the activation of the HPA axis in depression.

show abstract

Section: Sex Hormones Receptor Imbalancesupporting

confidence: 55%

Section: Sex Hormones Receptor Imbalancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, an androgen-responsive element (ARE), which initiated a repressing effect of AR on CRF expression, was identified in the CRF gene promoter region (Bao et al 2006). Similarly, our in vivo data showed that UCN1 exacerbated the inflammatory process in a rat model of vasculitis induced by sodium laurate ).…”

Section: Introductionsupporting

confidence: 51%

Dihydrotestosterone alters urocortin levels in human umbilical vein endothelial cells

Wan

Zhu

Guo

et al. 2013

Journal of Endocrinology

View full text Add to dashboard Cite

Urocortin (UCN1) is a member of corticotrophin-releasing factor (CRF) family, which has been proven to participate in inflammation. Previous work showed that dihydrotestosterone (DHT) could promote the inflammatory process. Little is known about the effect of DHT on UCN1 expression. The aim of our study is to investigate the effects and underlying mechanisms of DHT on endothelial UCN1 expression in the absence and presence of induced inflammation. Therefore, we tested the alterations of endothelial UCN1 expression treated with DHT in the presence or absence of lipopolysaccharide (LPS). Our data showed that DHT alone decreased UCN1 levels, which were attenuated in the presence of the androgen receptor (AR) antagonist flutamide. Conversely, in the presence of LPS, DHT augmented the LPS-induced increase in UCN1 expression, which was, interestingly, not affected by flutamide. When cells were treated with DHT alone, AR was upregulated and translocated into the nuclei, which might repress UCN1 expression via a potential androgen-responsive element found in human CRF family promoter. In the presence of LPS, DHT did not influence AR expression and location while it increased toll-like receptor 4 expression and activation, which was not altered by flutamide. DHTenhanced LPS-induced p38MAPK, ERK1/2, and nuclear factor kB pathway activation, which may contribute to the elevated expression of UCN1. These data suggest that DHT differentially influences UCN1 levels under normal and inflammatory conditions in human umbilical vein endothelial cells, which involves AR-dependent and -independent mechanisms respectively.

show abstract

“…Alternatively, orchidectomy in male rats increased hypothalamic CRH levels, which was reversed by testosterone treatment [442][443] . Likewise, the human CRH promotor contains response elements for both androgens and estrogens, and androgens repress CRH promotor activity, whereas estrogens promote CRH synthesis [444][445] . Also interactions between glucocorticoids and vitamin D 3 have been reported.…”

mentioning

confidence: 99%

Mapping the effects of vitamin D in multiple sclerosis

Rolf¹

View full text Add to dashboard Cite

Columbus (1451Columbus ( -1506 on one of his four voyages Er zijn verrassend veel parallellen te trekken tussen onderzoek doen en een van mijn favoriete vrijetijdsbestedingen, namelijk koken. Alles begint met een inspiratie, nieuwsgierigheid en een idee. Dan volgt de planning en de uitvoering en na (lang…) wachten kun je het resultaat proeven. Het blijft altijd spannend of het gelukt is en of het wel lekker is. Als het lekker is, dan smaakt het vaak ook naar meer! Zo niet, dan moet je het recept aanpassen, of crucialer, iets heel anders verzinnen...De weg naar een goed gelukt gerecht is, althans voor mij, minstens zo belangrijk: watertandend recepten zoeken en menu's samenstellen, op zoek gaan naar de juiste producten, lekker creatief combineren en (al of niet met succes) uitproberen. Dat kon ook in de voor mij nieuwe keuken van de wetenschap, en wel in een restaurant met een excellente ambiance. Verder is de diversiteit aan smaken, waar ik bij eten zo van houd, zeker ook terug te vinden in de verschillende hoofdstukken.Of kookkunsten gewaardeerd worden is vervolgens een kwestie van smaak, maar ook van kennis. De fijnproevers zullen zich op de details storten en boeren die het niet kennen zullen het niet eten, maar voor iedereen die aan tafel schuift: hopelijk is datgene wat in dit boekje geserveerd wordt smakelijk en levert het gespreksstof op voor het natafelen! Abbreviations and glossary & G L O S S A R Y AB BR EVI ATI ONS 23General IntroductionHistorical explorers discovered new land around the world, and with every journey more details have been added to global maps. For multiple sclerosis research, explorers of the 20 th century put vitamin D on the map, and from 2008 onwards, our research team in Maastricht has tried to add more details to this area. Today, vitamin D in multiple sclerosis is still an active area of research. Many reviews concentrate on the role of vitamin D in multiple sclerosis, illustrated by clinical and immunological studies. Also in this thesis two reviews elaborate on this topic. Therefore, the introduction to this thesis is restricted to the essential players, i.e. multiple sclerosis, its immune pathogenesis, and vitamin D, followed by the outline of the thesis.Multiple sclerosis (MS) is the most common disabling neurological disease among young people. Initial symptoms generally occur in the age of 20-40 years and MS affects women 2-3 times more often compared to men [1][2] . Currently, almost 1 in 1000 people suffers from MS in the Netherlands [3] . MS is characterized by inflammation and neurodegeneration of the central nervous system (CNS; brain and spinal cord). Though, it is still a matter of debate whether it is neurodegenerative or inflammatory from onset [1,4] . Most accepted, however, is the thought that inflammatory processes lead to damage of the fatty myelin sheaths covering the neuronal axons, which normally support fast transduction of signals, and this process is called demyelination. The inflammation can be accompanied by axonal injury and over time this result...

show abstract

A direct androgenic involvement in the expression of human corticotropin-releasing hormone

Cited by 105 publications

References 83 publications

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

Dihydrotestosterone alters urocortin levels in human umbilical vein endothelial cells

Mapping the effects of vitamin D in multiple sclerosis

Contact Info

Product

Resources

About