Class Of Hormones Research Articles

Regulation of Aryl Hydrocarbon Receptor Expression in Rat Granulosa Cells1

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates most of the toxic and endocrine-disruptive actions of aromatic compounds in the ovary. Paradoxically, this receptor has been shown to play important roles in normal female reproductive function as well. Although knowledge of AHR expression regulation in the ovary is of crucial significance to understand the receptor biology and its function in reproductive physiology, there are only limited data in this area. The purpose of the present study was to establish the possible regulation that AHR might undergo in ovarian cells. Here we show that the hormones FSH and estradiol are able to reduce AHR protein and transcript levels in granulosa cells in a way that parallels the changes observed in ovarian tissue across the rat estrous cycle. These findings suggest that estradiol and FSH would be cycle-associated endogenous modulators of AHR expression. In addition, we show that in granulosa cells the receptor is rapidly downregulated via proteasomal degradation following treatment with AHR ligands. However, prolonged treatment with an agonist caused an increase in Ahr mRNA levels. These actions would constitute a regulatory mechanism that both attenuates AHR signal rapidly and replenishes the cellular receptor pool in the long term. In conclusion, our results indicate that AHR expression is regulated by classical hormones and by its own ligands in granulosa cells.

Pharmacokinetics and systemic endocrine effects of the phyto‐oestrogen 8‐prenylnaringenin after single oral doses to postmenopausal women

Pre-clinical data suggest that the racemic phyto-oestrogen 8-prenylnaringenin (8-PN) may have beneficial effects in postmenopausal women and may become an alternative to classical hormone replacement therapy (HRT) treatment regimes. The aim of this study was to investigate the pharmacokinetics, endocrine effects and tolerability of chemically synthesized 8-PN in postmenopausal women. The study was performed using a randomized, double-blind, placebo-controlled, dose-escalation design with three groups of eight healthy postmenopausal women. In each group six subjects received 8-PN and two subjects placebo. 8-PN was given orally in doses of 50, 250 or 750 mg. Drug concentrations in serum, urine and faeces were measured up to 48 h and follicle-stimulating hormone/luteinizing hormone (LH) concentrations up to 24 h. All treatments were well tolerated and associated with a low incidence of (drug unrelated) adverse events. Serum concentrations of free 8-PN showed rapid drug absorption and secondary peaks suggestive of marked enterohepatic recirculation. Independent of the treatment group, approximately 30% of the dose was recovered in excreta as free compound or conjugates over the 48-h observation period. The first C(max) and AUC(0-48 h) showed dose linearity with ratios of 1 : 4.5 : 13.6 (C(max)) and 1 : 5.2 : 17.1 (AUC). The750- mg dose decreased LH concentrations by 16.7% (95% confidence interval 0.5, 30.2). Single oral doses of up to 750 mg 8-PN were well tolerated by postmenopausal women. The pharmacokinetic profile of 8-PN was characterized by rapid and probably complete enteral absorption, high metabolic stability, pronounced enterohepatic recirculation and tight dose linearity. The decrease in LH serum concentrations found after the highest dose demonstrates the ability of 8-PN to exert systemic endocrine effects in postmenopausal women.

Studies of Abscisic Acid Perception Finally Flower

The classical plant hormones (auxins, ethylene, gibberellins, cytokinins, and abscisic acid [ABA]) were discovered between 40 and 100 years ago, but it is only within the last ∼10 years that their receptors have been identified. The first two classes of receptors to be identified, those for

Expression of Corticosteroid-binding Protein in the Human Hypothalamus, Co-localization with Oxytocin and Vasopressin

Corticosteroid-binding globulin, a specific steroid carrier in serum with high binding affinity for glucocorticoids, is expressed in various tissues. In the present study, we describe the immunocytochemical distribution of this protein in neurons and nerve fibers in the human hypothalamus. CBG immunoreactive perikarya and fibers were observed in the paraventricular, supraoptic, and sexual dimorphic nuclei in the perifornical region, as well as in the lateral hypothalamic and medial preoptic areas, the region of the diagonal band, suprachiasmatic and ventromedial nuclei, bed nucleus of the stria terminalis and some epithelial cells from the choroid plexus and ependymal cells. Stained fibers occurred in the median eminence and infundibulum. Double immunostaining revealed a partial co-localization of corticosteroid-binding globulin with oxytocin and, to a lesser extent, with vasopressin in the paraventricular and the supraoptic nuclei. Double immunofluorescence staining showed coexistence of these substances in axonal varicosities in the median eminence. We conclude that neurons of the human hypothalamus are capable of expressing corticosteroid-binding globulin, in part co-localized with the classical neurohypophyseal hormones. The distribution of CBG immunoreactive neurons, which is widespread but limited to specific nuclei, indicates that CBG has many physiological functions that may include neuroendocrine regulation and stress response.

A systematic immunohistochemical survey of the distribution patterns of GH, prolactin, somatolactin, β–TSH, β–FSH, β–LH, ACTH, and α–MSH in the adenohypophysis of Oreochromis niloticus, the Nile tilapia

Fish pituitary plays a central role in the control of growth, development, reproduction and adaptation to the environment. Several types of hormone-secreting adenohypophyseal cells have been characterised and localised in diverse teleost species. The results suggest a similar distribution pattern among the species investigated. However, most studies deal with a single hormone or hormone family. Thus, we studied adjacent sections of the pituitary of Oreochromis niloticus, the tilapia, by conventional staining and immunohistochemistry with specific antisera directed against growth hormone (GH), prolactin (PRL), somatolactin (SL), thyrotropin (beta-TSH), follicle-stimulating hormone (beta-FSH), luteinising hormone (beta-LH), adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormone (alpha-MSH). The pituitary was characterised by a close interdigitating neighbourhood of neurohypophysis (PN) and adenohypophysis. PRL-immunoreactive and ACTH-immunoreactive cells were detected in the rostral pars distalis. GH-immunoreactive cells were present in the proximal pars distalis (PPD). A small region of the PPD contained beta-TSH-immunoreactive cells, and beta-LH-immunoreactive cells covered approximately the remaining parts. Centrally, beta-FSH-immunoreactive cells were detected in the vicinity of the GH-containing cells. Some of these cells also displayed beta-LH immunoreactivity. The pars intermedia was characterised by branches of the PN surrounded by SL-containing and alpha-MSH-immunoreactive cells. The ACTH and alpha-MSH antisera were observed to cross-react with the respective antigens. This cross-reactivity was abolished by pre-absorption. We present a complete map of the distinct localisation sites for the classical pituitary hormones, thereby providing a solid basis for future research on teleost pituitary.

Selective Modulators of PPAR Activity as New Therapeutic Tools in Metabolic Diseases

Peroxisome Proliferator Activated Receptors (PPARs) are regulators of metabolic pathways mainly of lipid metabolism and energy balance. Their medical importance is given by the fact that they have been implicated in development of insulin resistance, obesity and atherosclerosis. In recent years, major progress has been made in understanding the molecular basis of the function of these receptors. As a result of structural studies and identification of putative natural as well as synthetic ligands and activators of PPARs a new concept emerged and new drugs are on their ways to the clinic. The concept of Selective PPAR Modulators (SPPARM) was suggested by analogy to Selective Estrogen Receptor Modulators (SERM). SPPARMs activate the receptors in distinct ways leading to differential gene expression and biological response. The key features in understanding their action is most likely at the molecular details of ligand binding and the subsequently induced conformational changes as well as cofactor binding. A key aspect of this is that unlike classical steroid hormone receptors such as the retinoic acid receptor, the PPAR receptors have a rather large ligand-binding pocket which is not filled with the ligand entirely and the ligand also stabilizes the receptor's structure. The liganded receptor can have distinct conformations and this leads to different binding affinities for the various cofactors (coactivators and corepressors). In this review, we will introduce this concept, review the literature that supports it and present an overview of the receptor selective ligands including data about their mechanism of action and biological effects.

Modulation of alkaline phosphatases from Saccharomyces cerevisiae

We aimed at characterizing Saccharomyces cerevisiae alkaline phosphatases (ALPs) activity modulation by ALP activity classic inhibitors, cholesterol and steroid hormones as well as at identifying catalytic similarities between yeast and mammals ALPs. Saccharomyces cerevisiae expresses two ALPs, coded for PHO8 and PHO13 genes. PHO8 product is repressible by Pi in the medium. ALP activity from yeast (either grown in low or high phosphate medium) homogenates was determined with p-nitrophenylphosphate as substrate, pH 10.4 (lPiALP or hPiALP, respectively). L-Aminoacids and levamisole activated but EDTA and vanadate inhibited hPiALP, although with different patterns of effects. L-Homoarginine and L-tryptophan had a lower activatory effect on lPiALP. Corticosterone inhibited hPiALP but had the effect cancelled by growth on low phosphate medium. Cholesterol had a significantly different effect on hPiALP and lPiALP. beta-Estradiol and progesterone effects were different on hPiALP and lPiALP, showing a concentration-dependent activation of lPiALP (especially beta-estradiol). L-Homoarginine 5 mM was the stronger activator of hPiALP. L-Homoarginine 5 mM and beta-estradiol 5 mM may be used to discriminate between lPiALP and hPiALP. Our set of results does not allow identification of similarities between the behaviour of 2 Saccharomyces cerevisiae ALPs and any of the 4 human ALPs but allow us to raise the hypothesis of in vivo differential regulation of Saccharomyces cerevisiae ALPs by L-tryptophan, L-homoarginine and beta-estradiol.

The Origins of Cachexia in Acute and Chronic Inflammatory Diseases*

The term cachexia originates from the Greek root kakos hexis, which translates into "bad condition," recognized for centuries as a progressive deterioration of body habitus. Cachexia is commonly associated with a number of disease states, including acute inflammatory processes associated with critical illness and chronic inflammatory diseases, such as cancer, congestive heart failure, chronic obstructive pulmonary disease, and human immunodeficiency virus infection. Cachexia is responsible for the deaths of 10%-22% of all patients with cancer and approximately 15% of the trauma deaths that occur from sepsis-induced organ dysfunction and malnutrition days to weeks after the initial traumatic event. The abnormalities associated with cachexia include anorexia, weight loss, a preferential loss of somatic muscle and fat mass, altered hepatic glucose and lipid metabolism, and anemia. Anorexia alone cannot fully explain the development of cachexia; metabolic alterations in carbohydrate, lipid, and protein metabolism contribute to the severe tissue losses. Despite significant advances in our understanding of specific disease processes, the mechanisms leading to cachexia remain unclear and multifactorial. Although complex, increasing evidence from both animal models and clinical studies suggests that an inflammatory response, mediated in part by a dysregulated production of proinflammatory cytokines, plays a role in the genesis of cachexia, associated with both critical illness and chronic inflammatory diseases. These cytokines are further thought to induce an acute phase protein response (APR) and produce the alterations in lipid and carbohydrate metabolism identified as crucial markers of acute inflammation in states of malignancy and critical illness. Although much is still unknown about the etiology of cachexia, there is growing appreciation that cachexia represents the endproduct of an inappropriate interplay between multiple cytokines, neuropeptides, classic stress hormones, and intermediary substrate metabolism.

Plant bioactive peptides: an expanding class of signaling molecules

Until recently, our knowledge of intercellular signaling in plants was limited to the so-called five classical plant hormones: auxin, cytokinin, gibberellin, ethylene, and abscissic acid. Other chemical compounds like sterols and lipids have also been recognized as signaling molecules in plants, but it was only recently discovered that peptides in plants, as in animal cells, play crucial roles in various aspects of growth and development, biotic and abiotic stress responses, and self/non-self recognition in sporophytic self-incompatibility. These peptides are often part of a very large gene family whose members show diverse, sometime overlapping spatial and temporal expression patterns, allowing them to regulate different aspects of plant growth and development. Only a handful of peptides have been linked to a bona fide receptor, thereby activating a cascade of events. Since these peptides have been thoroughly reviewed in the past few years, this review will focus on the small putative plant signaling peptides, some often disregarded in the plant peptide literature, which have been shown through biochemical or genetic studies to play important roles in plants.

Steroid hormone mediated regulation of corticotropin-releasing hormone gene expression

Corticotropin-releasing hormone (CRH), a 41 amino acid polypeptide, is expressed in many regions of central nervous system and peripheral tissues and mediates many physiological functions. Abnormal production of CRH is involved in some pathological processes. Among various endogenous factors that modulate CRH production, steroid hormones control CRH production by regulating its gene transcription. Although there is no classical steroid hormone response element in the CRH promoter, steroid hormones regulate CRH gene expression through protein-protein interaction or by binding directly to response elements.

Be prudent in referring short children to endocrinologist

![Figure][1] Dr. Kaplowitz Evaluation of short children is the most common problem resulting in referral to pediatric endocrinologists. Among the large number of patients seen, endocrinologists do find an occasional child who has a hormonal problem, including classic growth hormone (GH)

An Aryl Hydrocarbon Receptor Agonist Amplifies the Mitogenic Actions of Estradiol in Granulosa Cells: Evidence of Involvement of the Cognate Receptors1

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that, besides mediating toxic responses, may have a central role in ovarian physiology. Studying the actions of AHR ligands on granulosa cells function, we have found that beta-naphthoflavone amplifies the comitogenic actions of FSH and 17beta-estradiol in a dose-dependent manner. This amplification was even greater in cells that overexpress the AHR and was reversed by cotreatment with the AHR antagonist alpha-naphthoflavone, suggesting that this effect is mediated by the AHR. The estrogen receptor is likewise implicated in this phenomenon, because a pure antiestrogen abolished the described synergism. However, the more traditional inhibitory AHR-estrogen receptor interaction was observed on the estrogen response element-driven transcriptional activity. On the other hand, alpha-naphthoflavone inhibited dose-dependently the mitogenic actions of FSH and 17beta-estradiol. Beta-naphthoflavone induced the expression of Cyp1a1 and Cyp1b1 transcripts, two well-characterized AHR-inducible genes that code for hydroxylases that metabolize estradiol to catecholestrogens. Nevertheless, the positive effect of beta-naphthoflavone on proliferation was not caused by increased metabolism of estradiol to catecholestrogens, because these compounds inhibited the hormonally stimulated DNA synthesis. This latter inhibition exerted by catecholestrogens suggests that these hydroxylases would play a regulatory point in granulosa cell proliferation. Our study indicates that AHR ligands modulate the proliferation of rat granulosa cells, and demonstrates for the first time that an agonist of this receptor is able to amplify the comitogenic action of classical hormones through a mechanism that might implicate a positive cross-talk between the AHR and the estrogen receptor pathways.

The effect of raloxifene and tibolone on the uterine blood flow and endometrial thickness: A transvaginal Doppler study

Objectives To evaluate and compare the effect of different than classical hormone therapy medications, such as raloxifene and tibolone, on the uterine arteries and endometrium of postmenopausal women using transvaginal ultrasonography. Methods The prospective study included 62 healthy, postmenopausal women recruited from the Menopausal Clinic of the 2nd Department of Obstetrics and Gynecology of the University of Athens. Subjects were randomly allocated to receive raloxifene HCl in a daily dose of 60 mg orally (Group A-31 women) or tibolone in a daily dose of 2.5 mg orally (Group B-31 women). The study period was 6 months and all subjects were assessed using transvaginal ultrasonography before treatment initiation as well as after 3 and 6 months for evaluation of the endometrial thickness and the pulsatility (PI) and resistance (RI) indices at the level of the uterine arteries. Results No significant differences in RI, PI and endometrial thickness were observed in the raloxifene group during the 6-month treatment. In the tibolone group, PI and RI values decreased linearly from baseline to the end of the study, whereas the endometrial thickness was significantly increased during the first 3 months remaining unaltered thereafter. Comparisons between the two study groups revealed significant percent change of values in the pre-treatment to month-3 period and no difference with regard to pre-treatment, month-3 and month-6 absolute values. Conclusion Raloxifene and tibolone exert dissimilar effects on uterine blood supply parameters and endometrial thickness.

Testis ecdysiotropic peptides in Rhodnius prolixus: Biological activity and distribution in the nervous system and testis

In Rhodnius prolixus, testes from both pharate adult and adult males are shown to produce and release ecdysteroids in vitro. Proteinaceous brain extracts from these stages caused stimulation of ecdysteroid production by testes of unfed adults. Therefore, the brain of Rhodnius contains peptides with testis ecdysiotropic activity. The Lymantria testis ecdysiotropin (LTE) also stimulated the in vitro production of ecdysteroids by unfed adult testis but had no stimulatory effect on prothoracic glands. Western blot analysis of brain peptides using anti-LTE revealed the presence of several medium to small size immunoreactive peptides. Two of these peptides with sizes of 16.8 and 11.0 kDa were present only during pharate adult development and the adult stage. Immunohistochemical analysis using confocal laser scanning microscopy revealed abundant LTE-immunoreactive material in cytoplasmic granules of specific neurosecretory cells in the brain and suboesophageal ganglion and the epithelium of the testis sheath. Clusters of two cytologically distinct cell types were seen within the medial neurosecretory cells (MNC) and also a pair of neurons in the posterior protocerebrum. Feeding in both larvae and adult males resulted in massive release of LTE-immunoreactive material from the MNC cells, suggesting a role of LTE-related peptides in both larval–adult development and in male reproductive development. Release from the MNC cells of LTE-immunoreactive material exhibited a clear daily cycling during larval–adult development, which was synchronous with the rhythms of release of prothoracicotropic hormone and bombyxin reported previously. The testis sheath exhibited intense immunofluorescence in pharate adults and unfed adults, which disappeared following a blood meal. It is concluded that LTE-related peptides are developmentally regulated in several locations and may act as ecdysiotropins in Rhodnius. Those in the MNC cells are very probably classical hormones, i.e. are transported to their target sites via the insect haemolymph.

Adrenocorticotropic Hormone-Mediated Signaling Cascades Coordinate a Cyclic Pattern of Steroidogenic Factor 1-Dependent Transcriptional Activation

Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that has emerged as a critical mediator of endocrine function at multiple levels of the hypothalamic-pituitary-steroidogenic axis. Within the adrenal cortex, ACTH-dependent transcriptional responses, including transcriptional activation of several key steroidogenic enzymes within the steroid biosynthetic pathway, are largely dependent upon SF-1 action. The absence of a bona fide endogenous eukaryotic ligand for SF-1 suggests that signaling pathway activation downstream of the melanocortin 2 receptor (Mc2r) modulates this transcriptional response. We have used the chromatin immunoprecipitation assay to examine the temporal formation of ACTH-dependent transcription complexes on the Mc2r gene promoter. In parallel, ACTH-dependent signaling events were examined in an attempt to correlate transcriptional events with the upstream activation of signaling pathways. Our results demonstrate that ACTH-dependent signaling cascades modulate the temporal dynamics of SF-1-dependent complex assembly on the Mc2r promoter. Strikingly, the pattern of SF-1 recruitment and the subsequent attainment of active rounds of transcription support a kinetic model of SF-1 transcriptional activation, a model originally established in the context of ligand-dependent transcription by several classical nuclear hormone receptors. An assessment of the major ACTH-dependent signaling pathways highlights pivotal roles for the MAPK as well as the cAMP-dependent protein kinase A pathway in the entrainment of SF-1-mediated transcriptional events. In addition, the current study demonstrates that specific enzymatic activities are capable of regulating distinct facets of a highly ordered transcriptional response.

100 years of hormonology: a view from No. 1 Wimpole Street

100 years of hormonology: a view from No. 1 Wimpole Street

Skeletal muscle wasting in tumor-bearing rats is associated with MyoD down-regulation

Cachexia is a syndrome characterized by profound skeletal muscle wasting that frequently complicates malignancies. A number of studies indicate that protein hypercatabolism, largely mediated by classical hormones and cytokines, is the major component of muscle depletion. Impaired regeneration has been suggested to contribute to the reduction of muscle size. In particular, it has been shown that the expression of MyoD, a muscle-specific transcription factor, is down-regulated by cytokines such as TNFalpha and IFNgamma in a NF-kappaB-dependent posttranscriptional manner. The present study investigated whether modulations of the transcription factor MyoD are associated with the onset of muscle wasting in a well established model of cancer cachexia. Rats bearing the Yoshida AH-130 hepatoma develop a condition of muscle protein hypercatabolism, largely dependent on TNFalpha bioactivity. In the gastrocnemius of these animals the expression of MyoD was markedly reduced, paralleling the decrease of muscle weight. This pattern is associated with increased nuclear translocation of AP-1, while DNA-binding assays did not detect any change in NF-kappaB activity. This is the first observation demonstrating that muscle depletion in tumor-bearing rats is associated with a down-regulation of MyoD levels. Although the underlying mechanisms remain to be clarified, this change is compatible with the hypothesis that a reduced expression of molecules involved in the regulation of the regenerative response may concur to muscle wasting in cancer cachexia.

Hormonal Regulation of Tomato Fruit Development: A Molecular Perspective

Fruit development is a complex yet tightly regulated process. The developing fruit undergoes phases of cell division and expansion followed by numerous metabolic changes leading to ripening. Plant hormones are known to affect many aspects of fruit growth and development. In addition to the five classic hormones (auxins, gibberellins, cytokinins, abscisic acid and ethylene) a few other growth regulators that play roles in fruit development are now gaining recognition. Exogenous application of various hormones to different stages of developing fruits and endogenous quantifications have highlighted their importance during fruit development. Information acquired through biochemical, genetic and molecular studies is now beginning to reveal the possible mode of hormonal regulation of fruit development at molecular levels. In the present article, we have reviewed studies revealing hormonal control of fruit development using tomato as a model system with emphasis on molecular genetics.

Clonidine vs. venlafaxine as treatment for hot flashes in breast cancer patients: A double-blind randomised study

8038 Background: Breast cancer patients are more susceptible to severe hot flashes due to the cytotoxic and endocrine treatment. This is one of the unsolved problems in cancer treatment because classical hormone replacement therapy is contraindicated in breast cancer especially in endocrine responsive disease. Patients and Methods: In a double blind, randomised phase III study 80 consecutive breast cancer patients (pts) who had hot flashes at least twice a day, and were not taking any medication against hypertension and depressions received either clonidine 0.075mg b.d. or venlafaxine 37.5mg b.d for four weeks. The primary endpoint is defined as frequency of hot flashes at week 5. The sample size in each group is 35 with alpha 0.1, one-sided significance level and 80% power. The null-hypothesis is defined as no difference between the groups, and the alternative hypothesis assumes a difference of 20%. A self reported one week hot flash and other symptom questionnaire was kept prior to the start of treatmen...

Body composition and time course changes in regional distribution of fat and lean tissue in unselected cancer patients on palliative care—Correlations with food intake, metabolism, exercise capacity, and hormones

Several investigations that yielded different results in terms of net changes in body composition of weight-losing cancer patients have been reported that employed a variety of methods based on fundamentally different technology. Most of those reports were cross-sectional, whereas to the authors' knowledge there is sparse information available on longitudinal follow-up measurements in relation to other independent methods for the assessment of metabolism and performance. For the current report, the authors evaluated time course changes in body composition (dual-energy X-ray absorptiometry) with measurements of whole body and regional distribution of fat and lean tissue in relation to food and dietary intake, host metabolism (indirect calorimetry), maximum exercise capacity (walking test), and circulating hormones in cancer patients who were receiving palliative care during 4-62 months of follow-up. The entire cohort comprised 311 patients, ages 68 years +/- 3 years who were diagnosed with solid gastrointestinal tumors (84 colorectal tumors, 74 pancreatic tumors, 73 upper gastrointestinal tumors, 51 liver-biliary tumors, 3 breast tumors, 5 melanomas, and 21 other tumor types). Decreased body weight was explained by loss of body fat, preferentially from the trunk, followed by leg tissue and arm tissue, respectively. Lean tissue (fat-free mass) was lost from arm tissue, whereas trunk and leg tissue compartments increased, all concomitant with declines in serum albumin, increased systemic inflammation (C-reactive protein, erythrocyte sedimentation rate), increased serum insulin, and elevated daily caloric intake; whereas serum insulin-like growth factor 1 (IGF-1), resting energy expenditure, and maximum exercise capacity remained unchanged in the same patients. Serum albumin levels (P < 0.001), whole body fat (P < 0.02), and caloric intake (P < 0.001) predicted survival, whereas lean tissue mass did not. Daily intake of fat and carbohydrate was more important for predicting survival than protein intake. Survival also was predicted by serum IGF-1, insulin, leptin, and ghrelin levels (P < 0.02 - P < 0.001). Serum insulin, leptin, and ghrelin (total) levels predicted body fat (P < 0.001), whereas IGF-1 and thyroid hormone levels (T3, free T3) predicted lean tissue mass (P < 0.01). Systemic inflammation primarily explained variation in lean tissue and secondarily explained loss in body fat. Depletion of lean arm tissue was related most to short survival compared with the depletion of lean leg and trunk tissue. The current results demonstrated that body fat was lost more rapidly than lean tissue in progressive cancer cachexia, a phenomenon that was related highly to alterations in the levels of circulating classic hormones and food intake, including both caloric amount and diet composition. The results showed importance in the planning of efficient palliative treatment for cancer patients.