| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
Endocrinology Unit, Department of Internal Medicine and Gastroenterology, St. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy
Address all correspondence and requests for reprints to: Prof. Renato Pasquali, Unita di Endocrinologia, Dipartimento di Medicina Interna and Gastroenterologia, Policlinico S. Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy. E-mail: rpasqual{at}almadns.unibo.it
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Multiple alterations of HPA axis activity in human abdominal obesity have been described, including altered ACTH pulsatile secretory dynamics (6) and hyperresponsiveness to different neuropeptides (7, 8, 9), insulin-induced hypoglycemia (10), acute mental stress challenges (11), and, possibly, selected dietary factors (12). In addition, obesity has been associated with several peripheral alterations of cortisol production and metabolism, including increased cortisol clearance (13), higher than normal cortisol turnover, and altered cortisol metabolism in adipose tissue, particularly visceral adipose tissue (14, 15). However, it is not known whether any or all of these changes represent a characteristic of the abdominal obesity phenotype or whether they may be due to other confounding factors associated with obesity not sufficiently evaluated, such as, for example, chronic anxiety or depression. Nevertheless, anxiety and depression are common features of obesity (16, 17) and are often associated with abnormalities of the HPA axis (18, 19, 20, 21). Thus, the psychological state of an individual may represent a confounding factor in the evaluation of the relationship between the HPA axis and different body fat distribution.
The purpose of this study was to investigate the activity of the HPA axis in nondepressed women with different obesity phenotypes. As in previous studies performed by our group (8, 9), the activity of the HPA axis was investigated by measuring both the response of cortisol and ACTH to combined administration of CRH and arginine vasopressin (AVP) (22) and the daily urinary excretion rate of free cortisol (UFC). The combined CRH/AVP test has an excellent intrasubject reproducibility in normal subjects (23), but a wide intersubject variation (24).
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This study included 36 obese women who consecutively underwent
an evaluation of their HPA axis in our clinic over an 18-month period.
All had a body mass index (BMI) greater than 28
kg/m2. Their general clinical profile is
summarized in Table 1
. These women were
referred to the Endocrine Unit of the Department of Internal Medicine
and Gastroenterology, University of Bologna, as out-patients, for the
evaluation and treatment of obesity. All had regular menses. Based on
clinical history, physical examination, and laboratory data, none of
them had diabetes, thyroid disease, hyperandrogenism (excluded by
clinical evaluation and basal androgen assessment), or cardiovascular,
renal, hepatic, or systemic diseases, nor were they taking medications.
For comparison, 10 normal weight women, regularly menstruating and
without history of having been overweight or obese, were also
investigated in parallel. None of the obese or control women were
smokers. All women gave their informed and written consent to the
study, which had been previously approved by the local ethics
committee.
|
The presence of depressive traits was investigated by two different questionnaires, the CDQ (25) and the CES-D (26), both in the Italian version. They are based on a numerical scale with a given threshold value assessing the presence or the absence of depression. In the CDQ scale, values lower than 7 exclude depression, as values lower than 21 do in the CES-D scale.
Anthropometry
Height was measured without shoes to the nearest 0.5 cm, and body weight was determined without clothes. The waist (W) and hip (H) circumferences were also measured, with the subjects standing, using a 1-cm-wide metal measuring tape, and the waist to hip ratio (WHR) was calculated. According to the recommendation of the WHO (27), waist circumference was measured as the minimum value between the iliac crest and the lateral costal margin, whereas hip circumference was determined as the maximum value over the buttocks. Women with WHR greater than 0.85 were defined as having abdominal obesity (A-BFD), and women with WHR less than 0.80 were defined as having peripheral body fat distribution (P-BFD) (27).
Evaluation of the activity of the HPA axis
Women were examined in the follicular phase between the 3rd and 10th days of the menstrual cycle. They followed their usual diet, which provided at least 250–300 g carbohydrates/day.
Blood tests were performed in the morning (0800–0830 h), after overnight fasting, while subjects had been quietly lying down for at least 15–20 min. An iv catheter for blood collection was placed in a forearm vein of one arm, and the vein was kept patent with NaCl (0.9%) infusion for at least 30 min. A single blood sample was obtained for baseline hormonal and biochemical parameter concentrations in all subjects. The activity of the HPA axis was examined by simultaneously administering CRH and AVP, as previously described (8). This procedure has been shown to maximally stimulate the pituitary ACTH reserve in physiological conditions (28). Human CRH (Novabiochem, Laufelingen, Switzerland) and synthetic AVP (Pitressin, Parke-Davis, Berlin, Germany) were injected as an iv bolus at doses of 100 µg and 0.3 IU, respectively. Blood samples for ACTH and cortisol determinations were drawn at -15 and 0 min before CRH and AVP administration and 5, 10, 15, 30, and 60 min thereafter. All women collected 24-h urine samples to measure the 24-h UFC excretion rate.
Baseline metabolic and hormonal evaluations
At baseline, blood samples were collected for glucose, insulin,
triglycerides, and high (HDL) and low (LDL) density lipoprotein
cholesterol determinations. Glucose and insulin values were used to
calculate the homeostasis insulin resistance index (HOMA), according to
the method of Emoto et al. (29). Several
studies have shown that the HOMA index has a good correlation with the
insulin sensitivity index obtained by the clamp technique and,
therefore, may also be used as marker of insulin resistance
(30). 
-Glutaryl transpeptidase (GT) was also
measured as a marker of hepatic steatosis, which is very common in
obesity and diabetes mellitus (31).
Hormonal and biochemical assays
The blood samples were placed in different tubes containing ethylenediamine tetraacetate, without or with aprotinin (500 U/mL), for cortisol and ACTH determinations, respectively, and were maintained in ice until centrifuged in a refrigerated centrifuge. Plasma aliquots for hormone determinations were then stored at -80 C until assayed. ACTH was determined with an immunoradiometric assay method using reagents obtained from Nichols Institute Diagnostics (San Juan Capistrano, CA). The sensitivity of this assay in our laboratory is approximately 0.22 pmol/L (1 pg/mL). Inter- and intraassay coefficients of variations at concentration levels of 6.3 pmol/L (28.6 pg/mL) and 53.8 pmol/L (244 pg/mL) were 9.6% and 7.1%, and 7.3% and 3.7%, respectively. Cortisol was determined by RIA with reagents obtained from Diagnostic Products (Los Angeles, CA). In our laboratory, the lowest sensitivity level is 83 nmol/L (30 ng/mL). Inter- and intraassay coefficients of variation at concentrations levels of 160.0 nmol/L (58 ng/mL), and 990.5 nmol/L (395 ng/mL) are 9.8% and 8.0%, and 1.4% and 4.1%, respectively.
Urine samples for UFC determinations were extracted with dichloroethane, and the extraction ratio was determined in 10% of the samples. The assays were performed using a fluorescent method in polarized light (system TDx) with reagents obtained from Abbott Laboratories (Chicago, IL) The lowest detection limit (Sto - 2 SD) in our laboratory was 1.4 pmol/dL. Intra- and interassay coefficients of variation were 6% and 8%, respectively. UFC values are expressed as nanomoles per m2 body surface area (UFC/m2). Plasma glucose concentrations were measured immediately by the glucose oxidase method (Glucose Analyzer II; Beckman Coulter, Inc., Fullerton, CA).
Plasma insulin was determined by RIA using a commercial kit
(INSIK-5, Sorin, Saluggia, Italy). Total cholesterol and
triglyceride levels were determined in plasma samples by enzymatic
methods using reagents obtained from Roche (Marburg, Germany). The HDL
cholesterol levels were measured after precipitation with
MgCl2·6H2O (0.05 mmol/L)
and phosphotungstenic acid (14 mmol/L) with reagents purchased from
Behring (Marburg, Germany). LDL cholesterol levels were calculated
according to the formula of Friedwald (32). GT was
measured by the St. Orsola-Malpighi Hospital Clinical Chemistry
Laboratory (Bologna, Italy).
Statistics
All results are reported as the mean ± SD. The intergroup comparisons were performed by ANOVA and covariance [body mass index (BMI) was used as a covariate in the comparisons between the two obese groups, because of their significantly different BMI values]. Pearson’s correlation coefficients and multiple regression analyses were used to investigate significant associations between different variables, always taking BMI values as an independent variable. The integrated hormone response to the CRH/AVP test was expressed as the area under the curve (AUC), which was calculated by the trapezoidal method. P < 0.05 was used to define statistical significance.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The results indicated the absence of significant depression/anxiety traits in all obese and control women included in the study. Therefore, all subjects had values lower than 7 in the CDQ scale and lower than 21 in the CES-D scale.
CRH/AVP test
There were no significant differences in basal ACTH concentrations
among the groups. Five minutes after peptide injection, ACTH rose
higher (P < 0.01) in the A-BFD group than in the P-BFD
and controls, without any significant differences observed between the
latter two groups (Fig. 1, top).
|
, bottom). These data were confirmed even after excluding the obese women with the highest BMI values, and both subgroups had similar mean BMI values (data not shown). The relations between WHR and cortisolAUC persisted even after adjusting for BMI values (r2 = 0.391; t = 2.386; P = 0.023).
Daily UFC/m2 excretion
As depicted in Fig. 2, UFC/m2 values were significantly lower in the
A-BFD group than in the P-BFD group (P < 0.05). No
significant relations between UFC/m2 and
cortisolAUC or ACTHAUC were
found either in the entire study population or in obese subjects
considered separately. Similar results were obtained when UFC values
were employed without correction for body surface area (data not
shown).
|
All metabolic parameters in the study population are reported in
Table 2. Obese women had significantly
higher total serum cholesterol (P < 0.01) and LDL
(P < 0.01) levels than controls, without any
significant difference among the obese subgroups. However, the A-BFD
group had significantly decreased (P < 0.05) HDL
cholesterol and increased triglyceride levels compared with both
controls and the P-BFD group. In addition, significantly higher values
of GT were found in the A-BFD group than in the control or P-BFD
group. Fasting insulin and HOMA index values were significantly higher
(P < 0.05) in both obese groups than in the controls,
and in the A-BFD than in the P-BFD group (P <
0.05).
|
All correlations were performed only in the obese subjects. A
significant correlation coefficient between
cortisolAUC and the HOMA index and fasting
insulin was found (r2 = 0.378; P
= 0.043 and r2 = 0.200; P <
0.05, respectively). CortisolAUC was also
positively correlated to BMI and WHR (r2 = 0.275;
P < 0.005 and r2 = 0.306;
P < 0.005, respectively; Fig. 3). CortisolAUC,
however, showed no significant correlation with total cholesterol, LDL
cholesterol, HDL cholesterol, triglycerides, or GT. A
significant correlation was found between
ACTHAUC, fasting insulin
(r2 = 0.334; P = 0.002) and the
HOMA index (r2 = 0.366; P =
0.003). On the other hand, UFC/m2 values were not
correlated with the HOMA index, whereas a borderline significant
negative correlation with fasting insulin levels was found
(r2 = 0.115; P = 0.090).
|
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The lower UFC values we found in the A-BFD group are consistent with an increase in the cortisol MCR in obesity, as previously described by Strain and co-workers (13). This could be due to multiple factors. The concentrations of the corticosteroid-binding globulin, which carries cortisol into the bloodstream, may be reduced in obesity, particularly in the abdominal phenotype (34). Moreover, glucocorticoid receptors are significantly more dense in visceral than sc adipocytes, and the increased trapping of cortisol could increase cortisol metabolic clearance as well (14, 35).
Finally, alterations of 11ß-hydroxysteroid dehydrogenase type 1
(11ßHSD1), which is localized in different tissues, particularly
liver and adipose tissue (36), where it catalyzes the
conversion of inactive cortisone to cortisol (37), and
5
-reductase type 1, which is particularly localized in the liver and
metabolizes cortisol to its tetrahydro derivatives (37),
should also be taken into account. In fact, recent studies performed by
Stewart and colleagues (38) in well characterized groups
of subjects with different degrees of obesity have provided evidence
for an inhibition of 11ßHSD1 in patients with increased central
adiposity, similar to what was previously observed in patients with
polycystic ovary syndrome (39). The association between
reduced 11ßHSD1 activity and abdominal obesity should not, however,
be surprising, as high doses of insulin inhibit this enzyme’s
expression (40). In addition increased 5-reductase type
1 activity, as indicated by an increased urinary excretion rate of
5-tetrahydrocortisol (41), has been reported in
abdominal obesity. This may further contribute to increased catabolism
of cortisol in extraadrenal tissues. Therefore, subtle abnormalities of
cortisol transport, function, and metabolism may help to explain the
reduced UFC we observed in women with abdominal obesity examined in
this study.
The results of the present study are also consistent with the concept that other factors, possibly central in origin, may be involved in determining HPA axis overresponsiveness in abdominal obesity. This may be suggested by the fact that we did not find any significant relation between the UFC/m2 values and hormone response to CRH/AVP in this report. This concept originates from studies carried out in experimental animals indicating that short- and long-term exposures to adverse environmental stressors are followed by a series of multiple neuroendocrine perturbations, including, in particular, increased activity of the HPA axis and the sympathetic nervous system (2, 42, 43). This kind of study in humans is difficult. On the other hand, preliminary studies performed by Bjorntorp’s group in a large cohort of middle-aged men provided convincing evidence for a strong association, at least in chronically stressed individuals, between daytime salivary cortisol levels and some subjectively perceived stress indexes, abdominal fat distribution, and several parameters of the metabolic syndrome (3, 44); this could suggest a loss of resiliency of the HPA axis and an increased CRH-ACTH drive. In addition, we have recently shown that the higher than normal ACTH response to CRH/AVP stimulation in subjects with abdominal obesity may be further enhanced by an acute and steady (for 2 h) increase in plasma norepinephrine at levels usually found during mild to moderate stress challenges, which suggests an increased sensitivity of the CRH and/or ACTH system to central noradrenergic regulation (45). Taken together, these data may provide some explanation for the hyperresponsiveness of the HPA axis to both acute (11) and chronic (3) stress factors in obese individuals.
On the other hand, as UFC represents an integrated measure of the free plasma cortisol over 24 h and, hence, is a measure of the feedback loop set-point of the HPA axis, the low UFC in A-BFD cannot exclude that subgroups of nondepressed patients with visceral obesity may be characterized by some forms of glucocorticoid hypersensitivity. Glucocorticoid hypersensitivity, in fact, may lead to abnormalities in systems that are more sensitive to glucocorticoids even under physiological conditions (46). Previous studies have shown a higher frequency of a particular restriction fragment length polymorphism of the glucocorticoid receptor gene in patients with visceral obesity (47), and this may reflect an increase in the glucocorticoid signal transduction system in this condition, leading to increased sensitivity to cortisol. Such increased hypersensitivity to glucocorticoids could help explain the lower UFC of the viscerally obese women compared with that of women with peripheral obesity. This attractive hypothesis, however, needs to be confirmed by more appropriate and detailed studies.
Another interesting finding of this study was that the cortisol response to the CRH/AVP challenge was significantly correlated with insulin levels and insulin resistance. The theoretical basis for this association does not necessarily imply a cause-effect relationship, granted that hyperinsulinemia and insulin resistance are common findings in obesity, particularly the abdominal phenotype. On the other hand, there are several reasons to suggest that increased HPA axis activity may play a role in favoring impaired insulin sensitivity. Indeed, glucocorticoid excess has multiple adverse actions on glucose metabolism (48). In addition to the insulin-resistant state that characterizes Cushing’s syndrome (49), manipulation of cortisol levels within the physiological range alters insulin sensitivity in healthy subjects (50), and a modest excess of glucocorticoid may contribute to insulin resistance in non-Cushing conditions in humans (5). In addition, cross-sectional studies have shown a significant association between higher than expected morning plasma cortisol with indexes of insulin resistance and glucose intolerance and with hypertriglyceridemia (4). Taken together, these findings are consistent with a primary role for increased HPA axis activity in determining insulin resistance and associated hyperinsulinemia.
On the other hand, it is possible that prevailing hyperinsulinemia, which is commonly observed in abdominal obesity and other insulin resistance syndromes, may be partly responsible for increased HPA axis activity. In fact, insulin crosses the blood-brain barrier (51). It has been demonstrated that the hippocampus represents a key area in the regulation of HPA axis activity and has a high insulin receptor concentration (52). Two recent studies examined this aspect in humans. Walker et al. (53) performed a CRH test during euglycemic clamp studies performed to obtain mild or moderate hyperinsulinemia in a mixed group of normal weight and overweight subjects, and they found that the peak cortisol response to CRH was diminished during the higher insulin clamp study. On the contrary, in normal weight subjects examined in similar experimental conditions, Fruehwald-Schulters et al. (54) found an increase in both basal cortisol and ACTH levels during a high insulin clamp study, suggesting a stimulatory effect of insulin on the HPA axis secretory capacity. Whether modest to severe hyperinsulinemia may represent a stimulatory factor of the HPA axis is therefore an unresolved question that needs to be further investigated.
In summary, we confirmed the presence of a significant correlation between HPA axis activity and both hyperinsulinemia and insulin resistance. Moreover, we have further demonstrated the presence of multiple alterations of the HPA axis in women with the abdominal obesity phenotype, consistent with coexistence of both central and peripheral alterations. It is important to note that these abnormalities were present in the absence of confounding factors capable of altering the HPA axis, such as anxiety or depression.
Received March 20, 2000.
Revised July 20, 2000.
Accepted July 31, 2000.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
2-adrenoreceptor regulation of the
hypothalamic-pituitary-adrenocortical axis in obesity. Clin Endocrinol
(Oxf). 52:413–421.[CrossRef][Medline]
This article has been cited by other articles:
 |
|
 |
|
  R H Straub, L B Tanko, C Christiansen, P J Larsen, and D S Jessop Higher physical activity is associated with increased androgens, low interleukin 6 and less aortic calcification in peripheral obese elderly women J. Endocrinol., October 1, 2008; 199(1): 61 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K A. H Iwen, O. Senyaman, A. Schwartz, M. Drenckhan, B. Meier, D. Hadaschik, and J. Klein Melanocortin crosstalk with adipose functions: ACTH directly induces insulin resistance, promotes a pro-inflammatory adipokine profile and stimulates UCP-1 in adipocytes J. Endocrinol., March 1, 2008; 196(3): 465 - 472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Vgontzas, S. Pejovic, E. Zoumakis, H.-M. Lin, C. M. Bentley, E. O. Bixler, A. Sarrigiannidis, M. Basta, and G. P. Chrousos Hypothalamic-Pituitary-Adrenal Axis Activity in Obese Men with and without Sleep Apnea: Effects of Continuous Positive Airway Pressure Therapy J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4199 - 4207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gambineri, L. Patton, R. De Iasio, F. Palladoro, U. Pagotto, and R. Pasquali Insulin-Like Factor 3: A New Circulating Hormone Related to Luteinizing Hormone-Dependent Ovarian Hyperandrogenism in the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2066 - 2073. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Golden, S. Malhotra, G. S. Wand, F. L. Brancati, D. Ford, and K. Horton Adrenal Gland Volume and Dexamethasone-Suppressed Cortisol Correlate with Total Daily Salivary Cortisol in African-American Women J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1358 - 1363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bousquet-Melou, E. Formentini, N. Picard-Hagen, L. Delage, V. Laroute, and P.-L. Toutain The Adrenocorticotropin Stimulation Test: Contribution of a Physiologically Based Model Developed in Horse for Its Interpretation in Different Pathophysiological Situations Encountered in Man Endocrinology, September 1, 2006; 147(9): 4281 - 4291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gambineri, V. Vicennati, S. Genghini, F. Tomassoni, U. Pagotto, R. Pasquali, and B. R. Walker Genetic Variation in 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Predicts Adrenal Hyperandrogenism among Lean Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2295 - 2302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Kok, S. W. Kok, M. M. Buijs, J. J. M. Westenberg, F. Roelfsema, M. Frolich, M. P. M. Stokkel, A. E. Meinders, and H. Pijl Enhanced circadian ACTH release in obese premenopausal women: reversal by short-term acipimox treatment Am J Physiol Endocrinol Metab, November 1, 2004; 287(5): E848 - E856. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gambineri, C. Pelusi, E. Manicardi, V. Vicennati, M. Cacciari, A. M. Morselli-Labate, U. Pagotto, and R. Pasquali Glucose Intolerance in a Large Cohort of Mediterranean Women With Polycystic Ovary Syndrome: Phenotype and Associated Factors Diabetes, September 1, 2004; 53(9): 2353 - 2358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lin, O. I. Bermudez, and K. L. Tucker Dietary Patterns of Hispanic Elders Are Associated with Acculturation and Obesity J. Nutr., November 1, 2003; 133(11): 3651 - 3657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Friedberg, E. Zoumakis, N. Hiroi, T. Bader, G. P. Chrousos, and Z.'e. Hochberg Modulation of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 in Mature Human Subcutaneous Adipocytes by Hypothalamic Messengers J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 385 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Z. Strowski, M. Kohler, H. Y. Chen, M. E. Trumbauer, Z. Li, D. Szalkowski, S. Gopal-Truter, J. K. Fisher, J. M. Schaeffer, A. D. Blake, et al. Somatostatin Receptor Subtype 5 Regulates Insulin Secretion and Glucose Homeostasis Mol. Endocrinol., January 1, 2003; 17(1): 93 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Vicennati, L. Ceroni, L. Gagliardi, A. Gambineri, and R. Pasquali Response of the Hypothalamic-Pituitary-Adrenocortical Axis to High-Protein/Fat and High-Carbohydrate Meals in Women with Different Obesity Phenotypes J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3984 - 3988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Rask, B. R. Walker, S. Soderberg, D. E. W. Livingstone, M. Eliasson, O. Johnson, R. Andrew, and T. Olsson Tissue-Specific Changes in Peripheral Cortisol Metabolism in Obese Women: Increased Adipose 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Activity J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3330 - 3336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pasquali, B. Ambrosi, D. Armanini, F. Cavagnini, E. D. Uberti, G. Del Rio, G. de Pergola, M. Maccario, F. Mantero, M. Marugo, et al. Cortisol and ACTH Response to Oral Dexamethasone in Obesity and Effects of Sex, Body Fat Distribution, and Dexamethasone Concentrations: A Dose-Response Study J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 166 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Nilsson, B.-M. Larsson, E. Jennische, E. Eriksson, P. Bjorntorp, D. A. York, and A. Holmang Maternal Endotoxemia Results in Obesity and Insulin Resistance in Adult Male Offspring Endocrinology, June 1, 2001; 142(6): 2622 - 2630. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS |
