scholarly journals 11β-Hydroxysteroid Dehydrogenase Type 1 Induction in the Arcuate Nucleus by High-Fat Feeding: A Novel Constraint to Hyperphagia?

Endocrinology ◽  
2006 ◽  
Vol 147 (9) ◽  
pp. 4486-4495 ◽  
Author(s):  
Valerie S. Densmore ◽  
Nicholas M. Morton ◽  
John J. Mullins ◽  
Jonathan R. Seckl
Keyword(s):  
Arcuate Nucleus ◽  
Hydroxysteroid Dehydrogenase ◽  
Endogenous Opioids ◽  
Opioid Antagonist ◽  
Mrna Levels ◽  
High Fat ◽  
Opioid Agonist ◽  
The Metabolic Syndrome ◽  
Melanocortin 4 Receptor

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes regeneration of active intracellular glucocorticoids in fat, liver, and discrete brain regions. Although overexpression of 11β-HSD1 in adipose tissue causes hyperphagia and the metabolic syndrome, male 11β-HSD1 null (11β-HSD1−/−) mice resist metabolic disease on high-fat (HF) diet, but also show hyperphagia. This suggests 11β-HSD1 may influence the central actions of glucocorticoids on appetite and perhaps energy balance. We show that 11β-HSD1−/− mice express lower hypothalamic mRNA levels of the anorexigenic cocaine and amphetamine-regulated transcript and melanocortin-4 receptor, but higher levels of the orexigenic melanin-concentrating hormone mRNAs than controls (C57BL/6J) on a low-fat diet (11% fat). HF (58% fat) diet promoted transient (∼8 wk) hyperphagia and decreased food efficiency in 11β-HSD1−/− mice and decreased melanocortin-4 receptor mRNA expression in control but not 11β-HSD1−/− mice. 11β-HSD1−/− mice showed a HF-mediated up-regulation of the orexigenic agouti-related peptide (AGRP) mRNA in the arcuate nucleus which paralleled the transient HF hyperphagia. Conversely, control mice showed a rapid (48 h) HF-mediated increase in arcuate 11β-HSD1 associated with subsequent down-regulation of AGRP. This regulatory pattern was unexpected because glucocorticoids increase AGRP, suggesting an alternate hyperphagic mechanism despite partial colocalization of 11β-HSD1 and AGRP in arcuate nucleus cells. One major alternate mechanism governing selective fat ingestion and the AGRP system is endogenous opioids. Treatment of HF-fed mice with the μ opioid agonist DAMGO recapitulated the HF-induced dissociation of arcuate AGRP expression between control and 11β-HSD1−/− mice, whereas the opioid antagonist naloxone given with HF induced a rise in arcuate AGRP and blocked HF-diet induction of 11β-HSD1. These data suggest that 11β-HSD1 in brain plays a role in the adaptive restraint of excess fat intake, in part by increasing inhibitory opioid tone on AGRP expression in the arcuate nucleus.

scholarly journals The importance of oxytocin mechanisms in the control of mouse parturition

Reproduction ◽  
2002 ◽  
pp. 543-552 ◽  
Author(s):  
AJ Douglas ◽  
G Leng ◽  
JA Russell
Keyword(s):  
Red Light ◽  
Endogenous Opioids ◽  
Beta Agonist ◽  
Early Gene ◽  
Opioid Antagonist ◽  
Dependent Manner ◽  
Birth Process ◽  
Opioid Agonist ◽  
Adrenergic Antagonist ◽  
Oxytocin Neurones

The role of oxytocin in parturition in mice was investigated. Pup birth profiles, blood samples and brains were collected from parturient mice observed under red light conditions in a reversed light:dark photoperiod. Peripheral administration of an oxytocin antagonist in a dose-dependent manner delayed the birth of subsequent pups, indicating that oxytocin is required for a normal pup birth profile. Oxytocin neurones were activated during birth as shown by both increased immediate early gene ( Fos) expression in oxytocin neurones in the supraoptic nucleus and increased plasma oxytocin concentrations during birth. In addition, the nucleus of the tractus solitarius and the olfactory bulbs, sites that process inputs to oxytocin neurones, become activated during parturition. Exposure to stress during parturition halted subsequent deliveries; at this stage plasma oxytocin concentrations were not higher than those of virgin mice, and birth was restored by administration of oxytocin. Administration of beta-adrenergic antagonist (propranolol) also restored stress-delayed birth, whereas administration of ritrodrine (beta-agonist) delayed birth in non-stressed mice, indicating that adrenergic mechanisms contribute to stress-delayed births in mice. Administration of morphine (mu-opioid agonist) delayed births transiently, but naloxone (opioid antagonist) did not prevent stress-delayed birth, indicating that endogenous opioids do not appear to contribute to neuroendocrine or uterine mechanisms that promote birth in mice. Therefore, despite evidence in oxytocin knockout mice that oxytocin is not essential for parturition in this species, the results of the present study indicate that oxytocin neurone activity and secretion contribute to the birth process in normal mice.

scholarly journals Tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 in overweight/obese women with polycystic ovary syndrome compared with weight-matched controls

2014 ◽  
Vol 171 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Alessandra Gambineri ◽  
Flaminia Fanelli ◽  
Federica Tomassoni ◽  
Alessandra Munarini ◽  
Uberto Pagotto ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Hydroxysteroid Dehydrogenase ◽  
Whole Body ◽  
Mrna Levels ◽  
Ovary Syndrome ◽  
Tissue Specific ◽  
Cortisol Metabolism ◽  
Cortisol Metabolites

ContextAbnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has been invoked as a cause of secondary activation of the hypothalamic–pituitary–adrenal axis and hence androgen excess. However, this is based on urinary excretion of cortisol metabolites, which cannot detect tissue-specific changes in metabolism and may be confounded by obesity.ObjectiveTo assess cortisol clearance and whole-body and tissue-specific activities of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) in PCOS.DesignCase–control study.SettingMedical center.PatientsA total of 20 overweight–obese unmedicated Caucasian women with PCOS, aged 18–45 years, and 20 Caucasian controls matched for age, BMI, body fat distribution, andHSD11B1genotypes (rs846910 and rs12086634).Main outcome measuresCortisol metabolites were measured in 24 h urine. During steady-state 9,11,12,12-[2H]4-cortisol infusion, cortisol clearance was calculated and whole-body HSD11B1 activity was assessed as the rate of appearance of 9,12,12-2H3-cortisol (d3-cortisol). Hepatic HSD11B1 activity was quantified as the generation of plasma cortisol following an oral dose of cortisone. Subcutaneous adipose HSD11B1 activity andHSD11B1mRNA were measured,ex vivo, in biopsies.ResultsUrinary cortisol metabolite excretion, deuterated cortisol clearance, and the rate of appearance of d3-cortisol did not differ between patients with PCOS and controls. However, hepatic HSD11B1 conversion of oral cortisone to cortisol was impaired (P<0.05), whereas subcutaneous abdominal adipose tissueHSD11B1mRNA levels and activity were increased (P<0.05) in women with PCOS when compared with controls.ConclusionsTissue-specific dysregulation of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased clearance of cortisol may result from obesity rather than PCOS.

Up-Regulation of mRNA Levels of 11β-Hydroxysteroid Dehydrogenase Type 1 in the Liver of Morbidly Obese Patients with Metabolic Syndrome

2011 ◽  
pp. P2-583-P2-583
Author(s):  
Esther Torrecilla-Garcia ◽  
Gumersindo Fernandez-Vazquez ◽  
David Vicent-Lopez ◽  
Franco Sanchez-Franco ◽  
Lucio Cabrerizo-Garcia ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Hydroxysteroid Dehydrogenase ◽  
Morbidly Obese ◽  
Mrna Levels ◽  
Obese Patients

Altered corticosteroid metabolism differentially affects pituitary corticotropin response

2002 ◽  
Vol 282 (2) ◽  
pp. E466-E473 ◽  
Author(s):  
Junko Hanafusa ◽  
Tomoatsu Mune ◽  
Tetsuya Tanahashi ◽  
Yukinori Isomura ◽  
Tetsuya Suwa ◽  
...  
Keyword(s):  
Glycyrrhizic Acid ◽  
Mrna Level ◽  
Hydroxysteroid Dehydrogenase ◽  
Corticotropin Releasing Factor ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Basal Plasma ◽  
Corticosterone Response ◽  
Pituitary Adrenal Axis

To evaluate the effects of altered corticosteroid metabolism on the hypothalamic-pituitary-adrenal axis, we examined rats treated with glycyrrhizic acid (G rats) or rifampicin (R rats) for 7 days. The half-life of exogenously administered hydrocortisone as a substitute for corticosterone was longer in G rats and shorter in R rats, with no differences in basal plasma levels of ACTH or corticosterone. The ACTH responses to human corticotropin-releasing factor (CRF) or insulin-induced hypoglycemia were greater in G rats and tended to be smaller in R rats compared with those in the control rats, whereas the corticosterone response was similar. No difference was observed in the content and mRNA level of hypothalamic CRF among the groups. The number and mRNA level of CRF receptor and type 1 11β-hydroxysteroid dehydrogenase (11-HSD1) mRNA level in the pituitary were increased in G rats but not changed in R rats, suggesting that chronically increased intrapituitary corticosterone upregulates pituitary CRF receptor expression. In contrast, CRF mRNA levels in the pituitary were increased in R rats. Our data indicate novel mechanisms of corticosteroid metabolic modulation and the involvement of pituitary 11-HSD1 and CRF in glucocorticoid feedback physiology.

Hexose-6-phosphate dehydrogenase in the endoplasmic reticulum

2010 ◽  
Vol 391 (1) ◽  
Author(s):  
Silvia Senesi ◽  
Miklos Csala ◽  
Paola Marcolongo ◽  
Rosella Fulceri ◽  
Jozsef Mandl ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Endoplasmic Reticulum ◽  
Pentose Phosphate Pathway ◽  
Hydroxysteroid Dehydrogenase ◽  
Pyridine Nucleotide ◽  
Pentose Phosphate ◽  
The Metabolic Syndrome ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract Hexose-6-phosphate dehydrogenase (H6PD) is a luminal enzyme of the endoplasmic reticulum that is distinguished from cytosolic glucose-6-phosphate dehydrogenase by several features. H6PD converts glucose-6-phosphate and NADP+ to 6-phosphogluconate and NADPH, thereby catalyzing the first two reactions of the pentose-phosphate pathway. Because the endoplasmic reticulum has a separate pyridine nucleotide pool, H6PD provides NADPH for luminal reductases. One of these enzymes, 11β-hydroxysteroid dehydrogenase type 1 responsible for prereceptorial activation of glucocorticoids, has been the focus of much attention as a probable factor in the pathomechanism of several human diseases including insulin resistance and the metabolic syndrome. This review summarizes recent advances related to the functions of H6PD.

scholarly journals 11β-Hydroxysteroid Dehydrogenase Type 1 and the Metabolic Syndrome

10.5772/28641 ◽  
2011 ◽  
Author(s):  
Cidalia D. ◽  
Maria J. ◽  
Isabel Azevedo ◽  
Rosario Monteiro
Keyword(s):  
Metabolic Syndrome ◽  
Hydroxysteroid Dehydrogenase ◽  
The Metabolic Syndrome
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