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markarian

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06.03.2007, 09:29

High basal serum allopregnanolone levels in overweight girls

http://www.nature.com/ijo/journal/v31/n3/abs/0803406a.html

High basal serum allopregnanolone levels in overweight girls

Zitat

B Predieri1, S Luisi2, E Casarosa3, M De Simone4, F Balli1, S Bernasconi5, M Rossi6, F Petraglia2 and L Iughetti1

1Department of Pediatrics, University of Modena and Reggio Emilia, Modena, Italy
2Department of Obstetrics and Gynecological, University of Siena, Siena, Italy
3Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Pisa, Italy
4Department of Pediatrics, University of L'Aquila, L'Aquila, Italy
5Department of Pediatrics, University of Parma, Parma, Italy
6Laboratory of Statistic, University of Parma, Parma, Italy
Correspondence: Professor L Iughetti, Department of Pediatrics, University of Modena and Reggio Emilia, Via del Pozzo, 71, Modena 41100, Italy. E-mail: iughetti.lorenzo@unimore.it

Received 19 December 2005; Revised 5 April 2006; Accepted 30 April 2006; Published online 18 July 2006.





Zitat

Objective:

Several studies demonstrated that obese subjects have a hyperactive hypothalamic-pituitary-adrenal axis and that sex steroid hormones have been closely related to the regulation of adiposity, either through direct or indirect physiological mechanisms. Allopregnanolone (3-hydroxy-5-pregn-20-one; AP) is a circulating neuroactive steroid hormone involved in the modulation of behavioral functions, stress and neuroendocrine axis. The aim of our study was to evaluate basal serum AP levels in obese children.
Subjects and measurements:

We studied 27 normal weight (NW) and 23 overweight (OW) girls. Gonadotropins and steroid hormones were assessed in all patients.
Results:

Basal AP concentrations in OW girls were significantly higher than in NW controls (P=0.013). There was no difference found between the other gonadal and adrenal hormones. Considering the pubertal stage, we demonstrated that obese pubertal girls presented higher AP concentrations than prepubertal and pubertal NW ones (P=0.020), and higher dehydroepiandrosterone sulfate (DHEAS) levels with respect to prepubertal obese girls, and prepubertal and pubertal NW patients (P=0.025). AP and DHEAS were significantly directly related to weight (r=0.31 and r=0.54, respectively) and body mass index (r=0.29 and r=0.34, respectively). In pubertal OW girls, a significant positive correlation between AP and DHEAS (r=0.60), A (r=0.72) and luteinizing hormone (r=0.64) levels was demonstrated.
Conclusion:

The present study demonstrates that AP is hypersecreted in children and adolescent with OW involving DHEAS concentrations, too. Our data suggest a possible role of AP in the regulation of neuroendocrine axis related to obesity. We can also speculate that in OW girls, who could manifest emotional and behavioral problems, a part of higher levels of this neuroactive steroid might act as -aminobutyric acid agonist producing anxiolytic-sedative effects.



Mehrere Studien zeigten, dass übergewichtige Personen eine hyperaktive Hypothalamus-Pituitary-Adrenal Achse haben und dass Sexualhormone entweder durch direkte oder indirekte physiologische Mechanismen einen engen Bezug zur Regulierung von Fettleibigkeit darstellen. Allopregnanolone ist ein zirkulierendes, neuraktives Steroidhormon, welches an die Modulierung von Verhaltensfunktionen, Stress und neurendokrine Achse beteiligt ist.

....

Die aktuelle Studie zeigt dass bei Kindern und Erwachsenen mit Übergewicht AP (Allopregnanolon) übersekretiert ("zuviel abgesondert") wird einschliesslich (erhöhter) Konzentration von DHEAS( Dehydroepiandrosteron Sulfat). Unsere Daten weisen auf eine mögliche Rolle von AP bei der Regulation der neuroendokrinen Achse in Bezug auf Übergewicht hin. Wir können bisher spekulieren, dass bei übergewichtigen Mädchen, bei denen sich emotionale und Vehaltensprobleme zeigen, ein Teil der höheren Levels dieses neuraktiven Steroid als Agonist von Aminobutyricsäure angstlösend- beruhigende Effekte auslösen.

Dieser Beitrag wurde bereits 2 mal editiert, zuletzt von »markarian« (06.03.2007, 09:31)


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06.03.2007, 09:34

Allopregnanolon

http://homepage.univie.ac.at/Michael.Ber…/6AcGb.htm#allo

Zitat

[3H]Allopregnanolon

KD im niedrigen nanomolaren Bereich
sehr lipophiler Ligand (cave Kunststoffe)
Steroid mit anästhetischer Wirkung ('non-genomic effects of steroids'), zum 1. Mal 1984 beschrieben, ähnlich Alphaxalon (Erhöhung der GABA-stimulierten Cl--Leitfähigkeit), bindet an eigene Steroid-Bindungsstelle am GABA-A-Rezeptorkomplex (TINS 22/9, 410). Allopregnanolon ist ein Metabolit des Progesterons. Progesteron hat in vivo ebenfalls anaesthetische Wirkung, wenn genügend Allopregnanolon gebildet wird, auch in Mäusen ohne intrazellulärem Progesteronrezeptor (Reddy & Apanites 2005, Brain Res. 1033:96).




Zitat

(3-hydroxy-5-pregn-20-one; AP)

k.A. ?

markarian

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06.03.2007, 09:50

http://www.ncbi.nlm.nih.gov/entrez/query…1&dopt=Abstract

Zitat

Pharmacology of endogenous neuroactive steroids.

Reddy DS.

Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina 27606, USA. samba_reddy@ncsu.edu

Neuroactive steroids are potent endogenous neuromodulators with rapid actions in the central nervous system. Neuroactive steroids have been claimed to have specific physiological roles in normal or pathological brain function. This article reviews the emerging evidence that progesterone-, deoxycorticosterone-, and testosterone-derived endogenous neuroactive steroids play an important role in the modulation of neural excitability and brain function. Neuroactive steroids such as allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC) are extremely potent positive allosteric modulators of GABAA receptors with sedative, anxiolytic, and anticonvulsant properties.The sulfated neuroactive steroids pregnenolone sulfate (PS) and dehydroepiandrosterone sulfate (DHEAS), which are negative GABAA receptor modulators, induce anxiogenic and proconvulsant effects. Thus, natural fluctuations in neuroactive steroid levels during the menstrual cycle and stress could affect several nervous system functions. There is strong evidence that allopregnanolone and THDOC are involved in the pathophysiology of premenstrual syndrome, catamenial epilepsy, major depression, and stress-sensitive brain disorders. Neuroactive steroids PS and DHEAS have been shown to modulate memory functions. However, the significance of the testosterone-derived neuroactive steroid 3alpha-androstanediol is not well understood. Like naturally occurring neuroactive steroids, synthetic derivatives such as ganaxolone have been proven in preclinical and clinical studies to be effective anticonvulsants with great potential for human use. Future research on inhibition or stimulation of specific neuroactive steroid synthesizing enzymes could provide an improved understanding and novel approaches for the treatment of anxiety, epilepsy, and depression.


http://www.ncbi.nlm.nih.gov/entrez/query…9&dopt=Abstract

Zitat

Neurosteroid modulation of GABAA receptors.

Lambert JJ, Belelli D, Peden DR, Vardy AW, Peters JA.

The Department of Pharmacology and Neuroscience, The Neuroscience Institute, Ninewells Hospital and Medical School, Dundee University, Dundee DD1 9SY, Scotland, UK. j.j.lambert@dundee.ac.uk

Certain metabolites of progesterone and deoxycorticosterone are established as potent and selective positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. Upon administration these steroids exhibit clear behavioural effects that include anxiolysis, sedation and analgesia, they are anticonvulsant and at high doses induce a state of general anaesthesia, a profile consistent with an action to enhance neuronal inhibition. Physiologically, peripherally synthesised pregnane steroids derived from endocrine glands such as the adrenals and ovaries function as hormones by crossing the blood brain barrier to influence neuronal signalling. However, the demonstration that certain neurons and glial cells within the central nervous system (CNS) can synthesize these steroids either de novo, or from peripherally derived progesterone, has led to the proposal that these steroids (neurosteroids) can additionally function in a paracrine manner, to locally influence GABAergic transmission. Steroid levels are known to change dynamically, for example in stress and during pregnancy. Given that GABA(A) receptors are ubiquitously expressed throughout the central nervous system, such changes in steroid levels would be predicted to cause a global enhancement of inhibitory neurotransmission throughout the brain, a scenario that would seem incompatible with a physiological role as a selective neuromodulator. Here, we will review emerging evidence that the GABA-modulatory actions of the pregnane steroids are highly selective, with their actions being brain region and indeed neuron dependent. Furthermore, the sensitivity of GABA(A) receptors is not static but can dynamically change. The molecular mechanisms underpinning this neuronal specificity will be discussed with particular emphasis being given to the role of GABA(A) receptor isoforms, protein phosphorylation and local steroid metabolism and synthesis.

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06.03.2007, 11:14

testosterone is usually elevated in obese individuals but that does not imply that testosterone makes you fat but that the body is counteracting overfeeding by transforming some of the excess calories into muscle mass. Of course the natural endocrine system is overwhelmed by the caloric input of today's sedentary individuals so they get fat nevertheless but hard training weightlifters can use the surge in androgens after overfeeding to build additional muscle mass in spite of a general hypocaloric state over a weekly period. Thats what a cyclic ketogenic diet is all about.

while in the mood of diet talk: http://www.elitefitness.com/forum/showpo…474&postcount=2
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