No abstract available.
Eating* ; Melanocortins*

INTRODUCTIONCommon obesity is a multi-factorial trait, contributed by the "obesogenic" environment of caloric abundance and increasing automation, sedentary lifestyle and an underlying genetic susceptibility. There have been major advances in the past decade in our understanding of the human weight regulation mechanism and pathogenesis of obesity, abetted by discoveries of genetic defects which lead to human obesity.

MATERIALS AND METHODSReports of genetic mutations causing obesity in humans and murine models were reviewed.

RESULTSHumans with genetic defects resulting in leptin deficiency, leptin receptor deficiency, proopiomelanocortin deficiency (POMC), and melanocortin 4 receptor (MC4R) deficiency developed severe obesity as the dominant phenotypic feature, though these are rare autosomal recessive conditions, except MC4R deficiency which is inherited in an autosomal co-dominant fashion. Common and rare variants of the POMC and melanocortin 3 receptor genes may be predisposing factors in the development of common obesity. Recent reports of human obesity associated with thyrosine kinase B (TrkB) defect and brain derived neurotrophic factor (BDNF) disruption, coupled with other murine studies, supported the role of BDNF/TrkB as effectors downstream of the melanocortin receptors.

CONCLUSIONDespite exciting discoveries of single gene mutations resulting in human obesity, most cases of obesity are likely the result of subtle interactions of several related genetic variants with environmental factors which favour the net deposition of calories as fat, culminating in the obese phenotype. The mechanisms of action of these genes in the development of obesity are now being examined, with the aim of eventually discovering a therapeutic intervention for obesity.

Animals ; Body Weight ; genetics ; Disease Models, Animal ; Humans ; Leptin ; genetics ; physiology ; Melanocortins ; genetics ; physiology ; Mice ; Mutation ; Obesity ; genetics

BACKGROUND: Rapid adrenocorticotropin (ACTH) stimulation test using 250ug of ACTH (1-24) has been used as a standard test in the initial assessment of adrenal function. However, it has recently been suggested that a rnaximal cortisol response can be achieved with a much lower ACTH dose, and reducing the dose might further enhance the sensitivity of the test in the detection of mild adrenal insufficiency. This study was performed to evaluate the role of low-dose (lug) ACTH stimulation test in the assessment of adrenal function and the diagnosis of subtle adrenal insufficiency. METHODS: Twenty-two subjects with suspected adrenal insufficiency due to long-term corticosteroid use were included in this study. The correlations between clinical features and the serum cortisol responses to low dose (lug) and high dose (250 ug) ACTH stimulation were evaluated. RESULTS: In high dose test, 10 (67%) out of 15 subjects with clinical features of adrenal insufficiency showed decreased serum cortisol response (peak cortisol level <18 ug/dL), but 5 (33%) subjects showed normal response (peak cortisol level > 18ug/dL). On the other hand, 14 (93%) subjects with clinical features of adrenal insufficiency showed decreased serum cortisol response in low dose test, while only one showed normal response. In 7 subjects without clinical features of adrenal insufficiency, 5 subject (71%) showed normal response, and 2 subjects (29%) showed decreased response in both low and high dose tests. CONCLUSION: These results suggest that the 1-ug low dose ACTH stimulation test might be more sensitive than conventional 250-ug test in the detection of mild adrenal insufficiency. Further studies are needed to determine the optimal dose of ACTH and the criteria for normal response to ACTH stimulation.
Adrenal Insufficiency* ; Adrenocorticotropic Hormone* ; Cosyntropin ; Diagnosis* ; Hand ; Hydrocortisone

BACKGROUND: Inhaled glucocorticoids are the medical treatment of choice in asthma patients. Fluticasone propionate is one of the most effective inhaled corticosteroids and has been reported to have minimal effect on the hypothalamic-pituitary-adrenal axis at the recommended dose. However, reports of long-term trials characterizing their systemic safety with chronic use are rare. This study was designed to evaluate the long-term safety of inhaled fluticasone propionate to the hypothalamic-pituitary-adrenal axis. METHOD: This study was conducted on 21 patients to evaluate the adrenal response to rapid ACTH stimulation test after 6 months of treatment with fluticasone propionate from 200 µg to 750 µg daily. The serum cortisol levels was measured to assess its effect on the hypothalamic-pituitary-adrenal axis just prior to the injection, at 30 minutes and 60 minutes after an intramuscular injection of synthetic ACTH. RESULT: The mean dose of inhaled fluticasone propionate was 355 µg per day(SD=174 µg, range=200 µg to 750 µg). The mean serum cortisol levels of the patients was 11.0 µg/dl(SD=6.4 µg/dl) prior to the injection, 20.0 µg/dl(SD=7.7 µg/dl) after 30 minutes, and 23.0 µg/dl(SD=6.3 µg/dl) after 60 minutes. Sixteen patients of the 21 patients had a normal response(>18 µg/dl), and 5 out of the 21 patients had serum cortisol levels below the normal range after the rapid ACTH stimulation test. CONCLUSION: Adrenal suppression occurred in 5 out of 21 patients with 6 months treatment with inhaled fluticasone propionate.
Adrenal Cortex Hormones ; Adrenocorticotropic Hormone ; Asthma* ; Axis, Cervical Vertebra* ; Cosyntropin ; Diethylpropion* ; Glucocorticoids ; Humans ; Hydrocortisone ; Injections, Intramuscular ; Reference Values ; Fluticasone

BACKGROUND: The effects of melanocyte stimulating hormone(MSH) on the integument of many species, including mammals, are well known. The significance of MSH as a physiological regulator of cutaneous pigmentation in humans is still controversial. Although the administration of MSH results in skin darkening, previous reports suggest that cultured human melanocytes are relatively unresponsive to this peptide. This may be related to the conditions under which the melanocytes were cultured. OBJECTIVE: The purpose of this study was to investigate the effect of alpha-MSH on the morphological changes, survival, and melanization of cultured human melanocytes in a basal medium without any mitogen. METHOD: We examined the morphological changes, number and melanin contents of cultured human melanocytes in control(absence of alpha-MSH) and experimental groups(presence of 10(-8) M, 10(-7) M, and 10(-6) M alpha-MSH). RESULTS: 1. There were no significant morphological changes of cells between the control and experimental groups after 24, 48, and 72 hours' culture. The number and length of melanocyte dendrites showed no significant difference between the groups after 24, 48, and 72 hours' culture. 2. The number of melanocytes in the experimental groups(presence of 10(-7) M, and 10(-6) M alpha-MSH) were significantly higher than the number of melanocytes in control group after 72 hours culture(p<0.05). This effect of alpha-MSH was dose-related. 3. The melanin contents slightly increased in the experimental groups. The significant difference between the groups was showed in the presence of 10(-8) M alpha-MSH. CONCLUSIONS: alpha-MSH has no effect on the morphology, but increases the survival of cultured human melanocytes and has a melanogenic effect.
alpha-MSH* ; Dendrites ; Humans* ; Mammals ; Melanins ; Melanocyte-Stimulating Hormones ; Melanocytes* ; Pigmentation ; Skin

No abstract available.
Adrenocorticotropic Hormone*

No abstract available.
Adrenocorticotropic Hormone*

No abstract available.
Adrenocorticotropic Hormone*

No abstract available.
Adrenal Insufficiency* ; Adrenocorticotropic Hormone*

No abstract available.
Adrenocorticotropic Hormone* ; Cortisone* ; Epinephrine*