Kristy

I'll post some links to interesting articles here: Brain hormone may hold key to memory loss, impaired cognition http://www.ucihealth.com/News/Releases/BrainHormone.htm Stress hormone-inhibitor drug can restore impaired memory caused by brain damage http://www.today.uci.edu/releases/01releases/189tv01.html Study links hormone, memory loss http://seattletimes.nwsource.com/news....98.html Study finds high level of stress hormone impairs memory http://www.cnn.com/HEALTH/9808/19/stress.memory/

And I thought it was cortisol....bet you did too. I'll be posting some of my other finds under this topic...tee hee Estrogens Here are some web links of interest: Neurendocrinology Briefings Number 6 Sex,Hormones, Mood, Mental State, and Memory http://www.neuroendo.org.uk/briefin6.htm Women under stress The role of estrogen in memory and learning http://ur.rutgers.edu/focus/index.phtml?Ar...=93&Issue_ID=13 UCSF Study Links Estrogen and Memory: http://www.ucsfhealth.org/news/hm_news/24aug00.htm ABCs Of Aging, Alzheimer's, Estrogen & Memory http://www.nymemory.org/menmemandmoo.html What Are the Effects on Mental Functioning with Estrogen Depletion? http://cbshealthwatch.medscape.com/cx/viewarticle/402943 Testosterone Hormone Replacement Therapy for Men? Testosterone & Male Menopause http://cbshealthwatch.medscape.com/cx/viewarticle/215365 Andropause Should Men With "Male Menopause" Symptoms Take Hormone Replacement Therapy? http://www.healthleader.uthouston.edu/archive/aging/010522/ Testosterone boosts verbal, spatial memory in small trial. Author/s: Andrew Bowser Urology Times Issue: Oct 1, 1998 http://www.findarticles.com/cf_dls....e.jhtml Alzheimer's Protein Increases When Testosterone Drops http://www.alzheimersupport.com/admin/pop_.../popfunding.cfm

Want to participate in a study at the NIH? http://clinicaltrials.gov/ct....tbb4eo1 Hippocampal Complex Volume and Memory Dysfunction in Cushing's Syndrome This study is currently recruiting patients. Sponsored by National Center for Research Resources (NCRR) University of Michigan

The second study is: STRESS AND HIPPOCAMPAL PLASTICITY Bruce S. McEwen Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10021; e-mail: mcewen@rockvax.rockefeller.edu KEY WORDS: glucocorticoids, NMDA receptors, dendrites, neurogenesis, memory, aging The hippocampus is a target of stress hormones, and it is an especially plastic and vulnerable region of the brain. It also responds to gonadal, thyroid, and adrenal hormones, which modulate changes in synapse formation and dendritic structure and regulate dentate gyrus volume during development and in adult life. Two forms of structural plasticity are affected by stress: Repeated stress causes atrophy of dendrites in the CA3 region, and both acute and chronic stress suppresses neurogenesis of dentate gyrus granule neurons. Besides glucocorticoids, excitatory amino acids and N-methyl-D-aspartate (NMDA) receptors are involved in these two forms of plasticity as well as in neuronal death that is caused in pyramidal neurons by seizures and by ischemia. The two forms of hippocampal structural plasticity are relevant to the human hippocampus, which undergoes a selective atrophy in a number of disorders, accompanied by deficits in declarative, episodic, spatial, and contextual memory performance. It is important, from a therapeutic standpoint, to distinguish between a permanent loss of cells and a reversible atrophy. *************************************** I am trying to find articles pertaining to humans...but if you want RAT studies...email me privately tee hee! You wouldn't believe the stuff I have run into! ***************************************

I will post summaries to studies that directly address the effects of cortisol on the brain. I have direct access to the full report(s). I can get them to you for your own personal use depending on the terms of the copywright. Please let me know if you want a copy by messenger, e-mail, or post if you want a full copy of the report. I will be adding more studies. The first study is The effects of chronic administration of hydrocortisone on cognitive function in normal male volunteers. Young AH, Sahakian BJ, Robbins TW, Cowen PJ. Department of Neuroscience and Psychiatry, Royal Victoria Informary, University of Newcastle upon Tyne, UK. A.H.Young@ncl.ac.uk RATIONALE: Corticosteroids are elevated in certain neuropsychiatric disorders and this may contribute to the neuropsychological impairments reported in these disorders. OBJECTIVE: To examine the effects of hydrocortisone on learning, memory and executive function. METHODS: Hydrocortisone 20 mg was administered twice daily for 10 days to normal male volunteers in a randomized, placebo control, crossover, within-subject design. Learning, memory and executive function were measured using selected subtests from the Cambridge Neuropsychological Test Automated Battery. RESULTS: Hydrocortisone caused impairments of visuo-spatial memory. These included increased within search errors and impaired use of strategies on the spatial working memory subtest. In addition, administration of hydrocortisone was associated with more errors in the paired associate learning subtest, although no effect was found on the Tower of London. Hydrocortisone speeded response latencies in certain tests (pattern and spatial recognition memory). CONCLUSION: These results indicate that chronic administration of hydrocortisone leads to deficits in certain tests of cognitive function sensitive to frontal lobe dysfunction and may contribute to the cognitive impairment reported in certain neuropsychiatric disorders. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 10494574 [PubMed - indexed for MEDLINE]

Thanks Sandy! If you have PCOS, Please look at this post under PCOS http://www.cushings-support.com/cgi-bin....opic=26 This talks about using Metaformin in the diagnostic use of PCOS and testosterone. Hmmmmmm.....

Just in time....I have been the listed insomniac here lately and even did another ufc last weekend. If this one is elevated, we're two for two and one more to go before we try the dex series again...hope the cycle holds.

Here is a web page I found while poking around the Endocrine Society. Mary O- this might be a good general link to add to the main page. http://www.uptodate.com/patient_info/topic...ryGlandHome.htm

You will need to go to your local medical library to see this one. I might be able to get a hard copy and send one snail mail for those interested...Let me know and I'll see what I can do!

:typing: Here is an in-depth paper about type II diabetes. I'm not kidding either...this stuff is real scienific receptors stuff that is way over the heads kind of discussion for most of us. It is interesting though. What I got out of it was that the drugs are designed to try to balance out the system so that the 'plugs' plug into the 'receptacles' tee hee "the yellow ones go here and the orange ones go here"...ha ha...just joking...for real though...if you are into deep thoughts about diabetes...this is pretty deep and probably more that what most of us mousekateers think about at 2 a.m. The burning question I always hear is "Why does glucophage upset my stomach!" Here is the link: http://edrv.endojournals.org/cgi....Here is the summary: Pathophysiology and Pharmacological Treatment of Insulin Resistance1 Stephan Matthaei, Michael Stumvoll, Monika Kellerer and Hans-Ulrich H?ring Department of Internal Medicine IV (Endocrinology, Metabolism, Angiology, Pathobiochemistry and Clinical Chemistry), University of T?bingen, D-72076 T?bingen, Germany Diabetes mellitus type 2 is a world-wide growing health problem affecting more than 150 million people at the beginning of the new millennium. It is believed that this number will double in the next 25 yr. The pathophysiological hallmarks of type 2 diabetes mellitus consist of insulin resistance, pancreatic ?-cell dysfunction, and increased endogenous glucose production. To reduce the marked increase of cardiovascular mortality of type 2 diabetic subjects, optimal treatment aims at normalization of body weight, glycemia, blood pressure, and lipidemia. This review focuses on the pathophysiology and molecular pathogenesis of insulin resistance and on the capability of antihyperglycemic pharmacological agents to treat insulin resistance, i.e., -glucosidase inhibitors, biguanides, thiazolidinediones, sulfonylureas, and insulin. Finally, a rational treatment approach is proposed based on the dynamic pathophysiological abnormalities of this highly heterogeneous and progressive disease. (Yeah - glucophage that upsets the stomach! yuk yuk) :vampire: (Edited by Kristy at 10:24 pm on Jan. 3, 2002)

1: Metabolism 2000 Jun;49(6):760-3 Related Articles, Books, LinkOut Circulating adrenomedullin is increased in patients with corticotropin-dependent Cushing's syndrome due to pituitary adenoma. Letizia C, Di Iorio R, De Toma G, Marinoni E, Cerci S, Celi M, Subioli S, D'Erasmo E. Department of Clinical Science, Second Institute of Obstetrics and Gynecology, University La Sapienza, Rome, Italy. It has been demonstrated that adrenomedullin, a newly discovered peptide with structural similarity to calcitonin gene-related peptide (CGRP), is expressed in pituitary gland and affects basal and corticotropin (ACTH)-releasing factor (CRF)-stimulated ACTH release in animals, thus suggesting its potential role in regulating the hypothalamus-pituitary-adrenal axis. To evaluate whether ACTH and cortisol levels affect adrenomedullin production in humans, we studied 14 patients with Cushing's syndrome due to pituitary adenoma and 8 patients with Cushing's syndrome due to adrenal tumor, with measurement of circulating adrenomedullin by a specific radioimmunoassay (RIA). Adrenomedullin concentrations were significantly higher in patients with pituitary adenoma (37.6 +/- 17.8 pg/mL) versus controls (13.7 +/- 6.1 pg/mL) and patients with adrenal adenoma (17.8 +/- 2.2 pg/mL). After pituitary surgical treatment, plasma adrenomedullin decreased significantly. In one patient with Cushing's syndrome due to pituitary adenoma who underwent simultaneous sampling of the inferior petrosal venous sinuses, the adrenomedullin concentration was significantly higher in plasma collected from the side with the adenoma and increased after CRF administration (delta increase, 42.6%), according to ACTH levels. Our findings indicate that circulating adrenomedullin is increased in Cushing's disease, and the pituitary gland may represent the site of the elevated production of adrenomedullin in this condition. Publication Types: Clinical Trial PMID: 10877203 [PubMed - indexed for MEDLINE] --------------------------------------------------------------------------------

Hmmmm.....seems to me all of this mousie-enzyme-cortisol stuff is getting exciting....but it is a little over my head. Maybe some ground breaking research is happening ya think? Maybe if a drug can be found to 'fix' the receptors...a non-invasive solution could be found for pituitary cushings!? Hmmmmmmm :typing: 1: J Clin Endocrinol Metab 2001 Jun;86(6):2728-33 Related Articles, OMIM, LinkOut, Books Expression of 11 beta-hydroxysteroid dehydrogenase isoenzymes in the human pituitary: induction of the type 2 enzyme in corticotropinomas and other pituitary tumors. Korbonits M, Bujalska I, Shimojo M, Nobes J, Jordan S, Grossman AB, Stewart PM. Department of Endocrinology, St. Bartholomew's Hospital, London, United Kingdom EC1A 7BE. One of the defining biochemical features of Cushing's disease is a relative insensitivity to glucocorticoid (GC) feedback, but an analysis of the GC receptor has failed to detect any major abnormalities. However, two isoenzymes of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD), either by converting cortisone (E) to cortisol (F) (type 1) or conversely by converting F to E (type 2), play an important prereceptor role in regulating corticosteroid hormone action at several sites. 11 beta HSD1 and -2 expression within the anterior pituitary gland itself may modulate GC feedback at an autocrine level, and we have speculated that this may be deranged in Cushing's disease. Detection of 11 beta HSD type 1 and 2 immunoreactive protein was performed using fluorescence immunohistochemistry. Double immunofluorescent studies were undertaken on normal pituitary to define the cellular localization of 11 beta HSD isoenzymes using antisera against GH, ACTH, LH, FSH, PRL, and S100, a nonhormonal marker of folliculo-stellate cells. In normal pituitary, positive staining for 11 beta HSD1-immunoreactive protein was observed in GH- and PRL-secreting cells and in folliculo-stellate cells; gonadotrophs, thyrotrophs, and ACTH-positive cells were negative. 11 beta HSD2 immunoreactivity was absent in all cell types. RT-PCR detected 11 beta HSD1 messenger ribonucleic acid (mRNA) expression in the normal pituitary; 11 beta HSD2 mRNA expression was also seen in most normal tissue. By contrast, in ACTH-secreting adenomas 11 beta HSD2 immunostaining was strongly positive in every case of corticotroph adenoma. 11 beta HSD1 immunoreactivity was also observed occasionally, but to a much lesser extent. In other pituitary tumors, both functional and nonfunctional, 11 beta HSD expression was variable in terms of isoenzyme mRNA and intensity of protein staining. The expression of 11 beta HSD1 (which generates F from E) in somatotrophs and lactotrophs suggests an autocrine role for this isoenzyme in the glucocorticoid regulation of pituitary GH and PRL secretion. 11 beta HSD2 expression is markedly induced in ACTH-secreting pituitary tumors and, by converting F to E, may explain the resetting of glucocorticoid feedback control in Cushing's disease. PMID: 11397878 [PubMed - indexed for MEDLINE]

:typing: I have the full PDF file on this (great to work for the university...let me know if you want it as it has some additional information not in this article.) Check out the whole website too..here's the link and the article: http://www.neuroendo.org.uk/briefin9.htm Summary Cushing's Disease is one of the most fascinating disorders in the whole of endocrinology, a minute tumour in the pituitary giving rise to a whole panoply of symptoms, signs, and changes in mood and behaviour. Recent research has begun to identify the molecular changes in these tumours underlying the reduced sensitivity of the tumour cells to normal feedback regulation and cell cycle control, and which may eventually lead to specfic gene therapy. -------------------------------------------------------------------------------- Cushing's Syndrome There are few situations more dramatic in clinical endocrinology than the remarkable transformation in appearance and behaviour associated with Cushing's syndrome. The body becomes centrally bloated, fat streams into the abdomen, while the muscles of the arms and legs wither. This disorder, first described by the Boston neurosurgeon Harvey Cushing in 1932, is a concatenation of symptoms and signs secondary to excessive exposure to a family of steroid hormones, the glucocorticoids. These hormones, principally cortisol, were originally identified as products of the adrenal gland, but in the 1950s their remarkable ability to inhibit inflammation was noted, and they rapidly became valuable therapeutic agents in diseases such as rheumatoid arthritis and asthma. Even today, the most common form of Cushing's syndrome is that due to over-zealous treatment with these steroids, either by mouth, by inhalers used for asthma, or even through the skin following the use of topical steroids for a whole variety of skin conditions. Cushing's Disease However, the most common cause of Cushing's syndrome in someone not taking any medication is that due to a small tumour of the pituitary gland, Cushing's disease. In this rare disorder, a small tumour of the pituitary (the master gland which sits underneath the brain, behind the eyes) makes too much of the hormone adrenocorticotrophin (ACTH) which in turn stimulates the adrenal glands to both grow and release excessive amounts of cortisol. The normal daily rhythm of cortisol release, with high blood levels peaking at 8 am and very low levels between midnight and 2 am, is disrupted, and it is this disturbed rhythm that is one of the hallmarks of Cushing's disease. In addition, the ability to switch off ACTH with glucocorticoids is deranged, and this relative insensitivity to feedback control is also made use of in diagnostic tests. A possible cause? Because Cushing's disease causes such widespread changes, it is usually diagnosed when the tumour is only a few millimetres in diameter. Such tumours are almost always 'monoclonal', that is, they represent a disordered proliferation of a single aberrant cell. If one cell undergoes a genetic change or mutation which allows it to make more ACTH than the surrounding cells, it may have a selective advantage. With time, the higher level of cortisol will switch off the other ACTH-secreting cells, or corticotrophs, allowing the monoclonal expansion to have a selective growth advantage. The suppression or atrophy of these surrounding cells had in fact been recognised by pathologists for many years. Unlike other more malignant tumours, which usually represent a whole series of progressive mutations, the small size of the tumours of Cushing's disease suggests that only one or possibly two changes of the cellular control machinery will have become disrupted. Recent work has begun to explore what these changes may be. -------------------------------------------------------------------------------- 'Such tumours are almost always 'monoclonal' ' -------------------------------------------------------------------------------- One approach has been to look at the normal feedback control of the corticotroph, and already there are suggestions that the way that the corticotroph senses circulating cortisol may be disturbed. For example, in rare instances levels of the receptor for cortisol, the glucocorticoid receptor, may be abnormally low, or mutated such that it does not work so effectively. More recently, evidence has been produced showing that an enzyme which inactivates cortisol may be over expressed. This may mean that the abnormal corticotroph will "see" less of the pervading cortisol in its immediate milieu, and secrete inappropriate amounts of ACTH. -------------------------------------------------------------------------------- 'We appear to be very near to precisely defining the molecular basis of this dramatic disease' -------------------------------------------------------------------------------- Alternatively, genes which generally regulate cell division, tumour suppressor genes (TSG), may be inactivated. One group has already shown that the TSG known as p16 may be switched off by a process referred to as methylation. In another series of studies, a TSG called p27 appears to form a protein which is rapidly broken down and is specifically under-expressed in ACTH-secreting tumours. Some other gene, known as an oncogene, may be selectively removing p27 from the cell nucleus thereby allowing its degradation by a "dustbin" pathway. We therefore appear to be very near to precisely defining the molecular basis of this dramatic disease. -------------------------------------------------------------------------------- Photomicrographs of pituitary tumours secreting growth hormone (left) or ACTH (right) stained for the tumour suppressor gene product, p27, in the cell nucleus. Note that only the growth hormone-secreting tumour contains significant quantities of p27 protein in the cell nuclei (brown colour). In the ACTH tumour, generally only the blue counterstain is visible in the smaller nuclei of these cells. Data of M.Korbonits, K.Lidhar, S.Jordan & A.B.Grossman -------------------------------------------------------------------------------- Is this important? While Cushing's disease is rare, with maybe one new case per quarter of a million population per year, glucocorticoids may cause disease in other more subtle ways. The oft-quoted relationship between stress and disease may be mediated in large part by cortisol, which may help explain the inverse association between social status and mortality. It has also been suggested that intrauterine or neonatal stress may imprint one's readiness to release cortisol, which may become clinically relevant in middle age. The obesity, hypertension and hyperlipidaemia so characteristic of the middle-aged in the developed world (and increasingly the developing world) may thus to a greater or lesser extent be glucocorticoid mediated. Increasing knowledge of the comparatively uncommon pituitary tumour causing Cushing's disease will undoubtedly expand our whole understanding of the impact of stress on survival. Author: Professor Ashley Grossman Department of Endocrinology St. Bartholomew's and the Royal London School of Medicine and Dentistry Queen Mary and Westfield College London (Edited by Kristy at 12:32 pm on Dec. 29, 2001) (Edited by Kristy at 12:50 pm on Dec. 29, 2001)

Check this out - Neeto! http://www.rockpointe.com/dem/phi.html (Edited by Kristy at 8:16 am on Dec. 15, 2001)

Oh yeah, and here is a movie too.... http://www.skullbaseinstitute.com/

Here is an article that talks even more about the process in depth. This is the procedure that I may be undergoing as I have been accepted. I just need to set the date. http://www.ast.org/06_publications/PDF/past/99-08.pdf

I can e-mail this study to anyone that wants it! A Transgenic Model of Visceral Obesity and the Metabolic Syndrome Hiroaki Masuzaki,1 Janice Paterson,23 Hiroshi Shinyama,1 Nicholas M. Morton,2 John J. Mullins,3 Jonathan R. Seckl,2 Jeffrey S. Flier1* The adverse metabolic consequences of obesity are best predicted by the quantity of visceral fat. Excess glucocorticoids produce visceral obesity and diabetes, but circulating glucocorticoid levels are normal in typical obesity. Glucocorticoids can be produced locally from inactive 11-keto forms through the enzyme 11 hydroxysteroid dehydrogenase type 1 (11 HSD-1). We created transgenic mice overexpressing 11 HSD-1 selectively in adipose tissue to an extent similar to that found in adipose tissue from obese humans. These mice had increased adipose levels of corticosterone and developed visceral obesity that was exaggerated by a high-fat diet. The mice also exhibited pronounced insulin-resistant diabetes, hyperlipidemia, and, surprisingly, hyperphagia despite hyperleptinemia. Increased adipocyte 11 HSD-1 activity may be a common molecular etiology for visceral obesity and the metabolic syndrome. 1 Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA. 2 Endocrinology Unit, Molecular Medicine Center, University of Edinburgh, Edinburgh, EH4 2XU, Scotland, UK. 3 Molecular Physiology Laboratory, University of Edinburgh, Edinburgh, EH8 9AG, Scotland, UK. * To whom correspondence should be addressed. E-mail: jflier@caregroup.harvard.edu (Edited by Kristy at 9:57 am on Dec. 10, 2001)

OBESITY RESEARCH: "Pot-Bellied Mice Point to Obesity Enzyme" Trisha Gura* Words linking fruit and the human anatomy have long sweetened sonnets and love letters. But lately the term "apple-shaped" has gained renown on the pages of medical texts. People who carry excess fat around their waists--the so-called apple-shaped body type--are more prone to obesity-related maladies than their equally overweight but pear-shaped counterparts, who pack weight around their hips. Physicians have observed the connection for decades, but no one could explain it, let alone search for a therapy to right the scales. Now on page 2166 (other post), researchers at Beth Israel Deaconess Medical Center in Boston suggest a reason for the disease-body type relationship, and a possible new target for treatment. The culprit is an obscure enzyme that works to recycle a steroid stress hormone called cortisol. Through delicate genetic engineering, endocrinologist Jeffrey Flier and his colleagues overexpressed the gene for this enzyme solely in the fat of mice. These rodents look and act a lot like overweight apple-shaped people: They eat more than normal mice and gain fat disproportionately around their middles. As adulthood sets in, the animals develop the early biochemical symptoms of heart disease and diabetes. Blocking the enzyme in people, the researchers suggest, might thwart obesity-related illnesses. -------------------------------------------------------------------------------- Belt loosener. Activating an enzyme in fat gives mice a syndrome seen in apple-shaped people. CREDIT: PHILIP HARVEY/CORBIS -------------------------------------------------------------------------------- "This was really the first proof that manipulating steroid conversion in fat alone is enough to lead to all these abnormalities," says endocrinologist Stephen O'Rahilly of Addenbrooke's Hospital in Cambridge, U.K., who studies the genetics of obesity and diabetes. "I wish I'd done the experiment myself." Inspiration for the study came indirectly from a rare illness called Cushing syndrome. Its sufferers have too much cortisol coursing through their bloodstreams and become diabetic and severely obese. For decades, endocrinologists hypothesized that common forms of obesity may represent very mild cases of Cushing syndrome. If so, most obese people should have higher than normal blood levels of cortisol--but researchers found that they don't and discounted the hypothesis. The theory was resurrected by Paul Stewart of the University of Birmingham in Edgbaston, U.K., whose group found that people have pockets of high cortisol activity. The team compared stress hormone production in two types of fat in 16 patients undergoing surgery, most of whom were of normal weight. One sample came from underneath the skin, the other from adipose tissue in the abdomen. In the belly fat, the researchers found higher activity of an enzyme called 11b hydroxysteroid dehydrogenase type 1 (11b HSD-1), which regenerates active cortisol from its inactive form, cortisone. Flier read a 1997 paper in The Lancet on the research and thought, "If we could make a mouse that overexpresses the enzyme only in fat, we could ask the question, 'Will that mouse get the apple-shaped body type and all its ill effects?' " he recalls. Visiting scientist Hiroaki Masuzaki engineered the mice; he linked a rat 11b HSD-1 gene to a promoter that turns on only in fat. The mice had 2.4 times more enzyme activity in their belly fat than did normal mice. Stress hormone levels in stomach fat tissue rose by 15% to 30%, but, as in most obese humans, bloodstream levels of the hormone were normal. As adulthood set in, the transgenic mice ate more, got fatter than normal mice, and carried the fat in their abdomens. Even when fed low-fat diets, the transgenics carried a spare tire that accounted for 37.9% of their total body fat compared with 27.5% in normal mice. The mice showed the hallmarks of early diabetes and hypertension: insulin resistance, renegade blood glucose levels, and other biochemical abnormalities. And a high-fat diet accelerated the pot-bellied rodents' downward spiral. "It is really the whole picture of what we refer to as the metabolic syndrome," says Flier, citing a term now in vogue in endocrinology circles to describe the growing population of obese people at risk for diabetes and heart disease. But O'Rahilly points out that no one can yet pin down 11b HSD-1 as the cause of the millions of cases of diabetes and heart disease. "You have to find out whether the level of metabolic disturbance in people correlates with the activity of this enzyme," O'Rahilly says. Meanwhile, two recent clinical observations support the team's results: In April, Joel Berger's group at Merck Research Laboratories in Rahway, New Jersey, showed that a class of antidiabetic drugs now on the market suppresses 11b HSD-1 levels in fat cells. And Eva Rask of Ume? University Hospital in Sweden and Brian Walker of the University of Edinburgh, U.K., report that obese men express higher levels of 11b HSD-1 activity in fat tissue than do lean males, which begins to address O'Rahilly's concerns. Flier and O'Rahilly both say they are aware of drug companies that have in hand, or are scrambling to come up with, potent inhibitors of the enzyme. Such compounds might be used to treat obesity by altering stress hormone levels in belly fat. "We have wanted to know for some time what properties of fat inside the abdomen make it different from fat outside the abdomen," says O'Rahilly. "If this enzyme explains it, that would be interesting indeed."

Lynne, I had it in my head to post it straight away as soon as I got back from my trip on Friday - I had to chuckle when not 5 minutes after I posted it, I saw the scan that MaryO had done of the clipping you had sent her! I was so really glad that someone else saw the article - Isn't it great! It almost seems that the research is starting to catch up with the disease....maybe in a few years there will be a non-invasive therapy available for hypercortisolism that works on the cellular level. :biggrin:

Enzyme May Be Target for Future Obesity Drug December 06, 2001 02:07 PM ET ? ? By Maggie Fox, Health and Science Correspondent WASHINGTON (Reuters) - A stress-related hormone may hold the key to the most dangerous type of obesity -- the so-called apple-shaped syndrome in which people get fat bellies and often diabetes, high blood pressure and heart disease, researchers said on Thursday. They hope drugs can be designed that can help control the hormone and perhaps stave off the dangerous results of such obesity. "This has the flavor of something that may be a mechanism that contributes importantly to typical obesity," said Dr. Jeffrey Flier of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, who led the study, published in Friday's issue of the journal Science. More than 60 percent of Americans are overweight and more than a quarter are obese, meaning they have a high risk of health problems linked to their weight, according to the U.S Centers for Disease Control and Prevention (CDC). Many studies have shown that it is often easy to tell who is most at risk by measuring waist circumference. This points to visceral fat, a build-up of fat inside the abdomen that is associated with the most dangerous effects of obesity. People with a rare disease called Cushing's syndrome have too much abdominal fat as well as diabetes and high blood pressure, Flier said in a telephone interview, but the condition looks a lot like common obesity. "This obvious fact caused many scientists and companies to wonder if it is possible that many patients with obesity have a mild form of Cushing's syndrome," he said. "That question has been asked over and over again." The answer, however, is no. Cushing's is characterized by a high level of the stress hormone cortisol in the blood, and most obese people have normal levels. ENZYME REACTIVATES STRESS HORMONE Researchers studied the role of stress hormones and enzymes that affect them. One of particular interest was HSD-1. Cortisol is deactivated by several enzymes, but HSD-1 can reactivate it inside a cell. Flier saw work by British researchers that suggested this could happen only in fat cells. "They raised the idea that you make too much (cortisol), but only in the abdominal fat cell itself," he said. If this was happening, it would explain why some obese people have the extra abdominal fat without extra cortisol in their blood. "The way I went about proving it with my colleagues was to create a genetic experiment and take a normal mouse, force the mouse to have more than normal level of this enzyme activity, but only in its fat cells," said Flier, who worked with Janice Paterson and colleagues at the University of Edinburgh. "We got exactly, even more than we bargained for." The mice were fat and ate more than normal mice. "On top of that they developed diabetes, they developed high lipids in the blood (high cholesterol). They also developed high blood pressure," Flier said. At the same time, British researchers reported they found the more fat people had in their bodies, the higher the level of the same enzyme, HSD-1, in their fat cells. The enzyme was working only in the fat cells, not in the rest of the body. It was like a localized version of Cushing's syndrome. "We don't know why some people have more of this enzyme activity than others," Flier said, adding that he thought it could be a combination of genes, diet and exercise. The immediate thought was that if a drug could stop the effects of the enzyme, people with the apple-shaped obesity problems could be helped. Flier said several pharmaceutical companies, which he declined to name, are already working on such a drug. He said another British team had genetically engineered mice that do not make any HSD-1 and they are healthy. "You don't need the enzyme to live, which is good, and what is more, they reported ... when you put them on a high-fat diet, which normally makes an animal a little bit diabetic, those mice don't get diabetes." Flier said he did not believe HSD-1 would turn out to be like another hormone linked with obesity -- leptin. Obese rats lost weight when injected with leptin, raising hopes that leptin might be an easy diet pill. But obese humans were found to have above normal leptin levels and giving them additional leptin had little or no effect on their weight. Flier says this one feels different. "Even though I can't prove it, I have a personal feeling this one will lead to something," he said.

:wow: I had heard that some research was getting ready to break. This is wonderful news! Soon, acromegly may be able to me treated with medication and surgery only to remove the tumor. Non-invasive means of treating the disease is an excellent avenue. Thanks for posting!

Here it is: Professional Guide to Signs & Symptoms List Price: ฺ.95 from Amazon.com Book Info Brandon/Hill Nursing List selection (#231). Guide to more than 550 signs and symptoms with nursing implications in a concise format. For nurses. More than 500 illustrations, flowcharts, tables, and reproducible patient teaching aids are also included. A-to-Z organization for quick access. Previous edition: c1997. DNLM: Nursing Assessment--methods--Handbooks.

I found this site yesterday looking for some new information about pituitary tumors. It is designed to be a teaching file. I found it to be on the human scale (so many are on the scientist scale). I hope you like it. http://www.neuro.hscsyr.edu/neuro/teachfil...ry/index-.shtml (Edited by Kristy at 5:20 pm on Nov. 13, 2001)

I found at book at Waldenbooks last night - shoot, I should have bought it. It was a book that listed all the symptoms to different disorders. It even listed Cushings (which impressed me at the time). I know it isn't a web site, but at least it is portable. I'll get the title for you. Kristy

This site is a terriffic place to find all about diabetes. http://www.focusondiabetes.com/Script....They even discuss it with Cushings! "Diabetes can also result from other hormonal disturbances, such as excessive growth hormone production (acromegaly) and Cushing's syndrome. In acromegaly, a pituitary gland tumor at the base of the brain causes excessive production of growth hormone, leading to hyperglycemia. In Cushing's syndrome, the adrenal glands produce an excess of cortisol, which promotes blood sugar elevation."