Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Hormone sensitive”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed2005

Open-label trial evaluating the safety and efficacy of zoledronic acid in preventing bone loss in patients with hormone-sensitive prostate cancer and bone metastases.

OBJECTIVES: To evaluate the efficacy and safety of zoledronic acid in preventing bone loss in patients with hormone-sensitive prostate cancer and bone metastases who were receiving androgen deprivation therapy. METHODS: Patients received zoledronic acid 4 mg as a 15-minute infusion every 3 weeks for 1 year. Bone mineral density of the lumbar spine (L2 to L4) and total hip was measured by dual-energy x-ray absorptiometry at baseline and 12 months. Biochemical markers of bone turnover (N-telopeptide and bone alkaline phosphatase) and serum creatinine levels were evaluated at baseline and during the study. Skeletal-related events were assessed at each study visit. RESULTS: Of the 221 enrolled patients, 202 and 221 patients were included in the efficacy and safety analyses, respectively. The mean increase in bone mineral density of the lumbar spine and total hip was 7.7% (P <0.001) and 3.6% (P <0.001), respectively. Decreases in N-telopeptide and bone alkaline phosphatase levels were significant and sustained. The median time to the first skeletal-related event was not reached; 11.9% of patients had a skeletal-related event. Arthralgia (20.4%), nausea (14%), fatigue (14%), and back pain (12.2%) were the most common adverse events. Adverse events due to renal function deterioration were infrequent. The mean maximal change in serum creatinine level from baseline was 0.3 mg/dL. CONCLUSIONS: Zoledronic acid administration for 1 year to patients with hormone-sensitive prostate cancer and bone metastases who were receiving androgen deprivation therapy was safe and prevented bone loss, as demonstrated by significant increases in bone mineral density and sustained suppression of biochemical markers of bone turnover.

Aged↗
PubMed2004

Hormone-sensitive lipase--new roles for an old enzyme.

Although described initially as an intracellular adipocyte-specific triacylglycerol lipase, it is now clear that HSL (hormone-sensitive lipase) is expressed in multiple tissues and plays a number of roles in lipid metabolism, including that of a neutral cholesteryl ester hydrolase. The major isoform is a single polypeptide with a molecular mass of approx. 84 kDa and which comprises three major domains: a catalytic domain, a regulatory domain encoding several phosphorylation sites and an N-terminal domain involved in protein-protein and protein-lipid interactions. The activity of HSL is regulated acutely by several mechanisms, including reversible phosphorylation by a number of different protein kinases, translocation to different sites within the cell and interaction with a number of proteins, some of which may serve to direct the inhibitory products of HSL away from the protein. It is also apparent from work with HSL null mice that more than one enzyme species may be classified as a hormone-sensitive lipase. The possible presence of HSL in macrophages remains controversial, and the role of the protein in pancreatic beta-cells has yet to be fully elucidated. Altered expression of HSL in different cell types may be associated with a number of pathological states, including obesity, atherosclerosis and Type II diabetes.

Adipocytes↗
PubMed1999

Approaches to the treatment of patients with hormone-sensitive prostate cancer.

Androgen ablation therapy provides effective palliation for patients with advanced cancer of the prostate for only a short duration because the tumor eventually develops resistance. Among the many potential molecular mechanisms involved in the development of tumor resistance to both androgen ablation therapy and chemotherapy, mutations in the p53 tumor suppressor gene, overexpression of the antiapoptotic protein bcl-2, and overexpression of the multidrug resistance protein probably play a role. Because hormone-resistant tumors demonstrate greater expression of bcl-2 and because transfection of the bcl-2 gene into hormone-sensitive tumor cells confers resistance to both hormone therapy and chemotherapy, efforts to abrogate bcl-2 in prostate tumors represent one approach to improve clinical results. Of several agents recently shown to reduce prostate-specific antigen levels in phase II studies, 13-cis-retinoic acid and interferon-alpha can reduce the expression of bcl-2 and overcome bcl-2-mediated resistance to paclitaxel in resistant cell lines. For these reasons, our current studies test the hypothesis that reducing the expression of bcl-2 with 13-cis-retinoic acid and interferon-alpha in combination with taxanes will improve clinical results. Additionally, other studies test the hypothesis that treatment early, before the development of resistance mechanisms, in hormone-sensitive disease will improve results. Studies with docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) and with estramustine combination therapy are also ongoing.

Animals↗
PubMed2001

Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells.

Norepinephrine induced lipolysis in rat fat cells, in vitro, in a time- and concentration-dependent manner, without concomitantly increasing hormone-sensitive lipase (HSL) activity. It also induced, time and concentration dependently, HSL translocation from the cytosol to the lipid droplets in fat cells. Isoproterenol, forskolin, dibutyryl cyclic AMP, and theophylline also induced lipolysis in fat cells, but did not stimulate HSL activity. These agents also induced HSL translocation from the cytosol to the lipid droplets in fat cells: about 80% to 90% of all HSL was located in lipid droplets after incubation for 1 h. These results suggest that the critical event in lipolytic activation of fat cells induced by lipolytic agents is not an increase in the catalytic activity of HSL but translocation of HSL to its substrate on the surfaces of lipid droplets in fat cells.-Morimoto, C., K. Kameda, T. Tsujita, and H. Okuda. Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells. J. Lipid Res. 2001. 42: 120;-127.

Adipocytes↗
PubMed1986

Effect of dietary saturated fatty acids on hormone-sensitive lipolysis in rat adipocytes.

The objective of this work was to examine the mechanism by which dietary saturated fatty acids, as compared with polyunsaturated fatty acids, lower hormone-sensitive lipolysis in rat adipocytes. Rats were fed a purified diet containing 14% of a fat with a high concentration of either saturated fatty acids (coconut oil or beef fat) or polyunsaturated fatty acids (safflower oil) as a control. In addition, each diet contained 2% corn oil. The animals were fed these diets for 4 wk. Norepinephrine-stimulated lipolysis was 50% lower when diets rich in saturated fatty acids, regardless of their chain length, were fed than when a diet containing a high concentration of polyunsaturated fatty acids was fed. The specific activities of adenylate cyclase, 3',5'-cyclic nucleotide (cAMP) phosphodiesterase and hormone-sensitive lipase were lower when saturated fatty acids were fed than when polyunsaturated fatty acids were fed. Accumulation of cAMP upon stimulation with 10(-5) M norepinephrine was lower when saturated fatty acids were fed than when polyunsaturated fatty acids were fed. Moreover, adipocytes were larger when saturated fatty acids were fed than when polyunsaturated fatty acids were fed. The data obtained suggest that dietary saturated fats exert their inhibitory effect on hormone-stimulated lipolysis by influencing several points in the lipolytic cascade.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Use of protein G for preparation and characterization of rabbit antibodies against rat adipose tissue hormone-sensitive lipase.

The newly described immunoglobulin G-binding streptococcal surface protein, protein G, was used to prepare and characterize rabbit antibodies. The antibodies were directed against rat hormone-sensitive lipase, the rate-limiting enzyme in the hydrolysis of the triacylglycerols stored in adipose tissue. Antiserum was obtained after two injections with 20 micrograms enzyme protein, and the immunoglobulin fraction was obtained using a protein G-based solid-phase radioimmunoassay. The hydrolysis of acylglycerols by the enzyme was inhibited by the antibodies, and the enzyme could be efficiently removed from a solution using the antibodies and heat-killed streptococci expressing surface protein G. By Western blot and detection with 125I-protein G, the antibodies were found to selectively bind to hormone-sensitive lipase and to a smaller extent to two minor contaminants, possibly proteolytic fragments of the lipase. The amount of 125I-labelled protein G bound to the lipase on the blot was quantitatively related to the amount of enzyme protein down to the detection limit 10 ng.

Adipose Tissue↗
PubMed2006

[Effect of different post-weaning dietary compositions on body fat content and hormone-sensitive lipase gene expression in rats fed with high-fat diet].

OBJECTIVE: To study the effects of different postweaning dietary compositions on body fat content and hormone-sensitive lipase (HSL) gene expression in rats fed a high-fat diet. METHODS: Male Wistar rats weaned on 24 days were randomly divided into A, B, C, D groups and were fed on high carbohydrate, high protein, high unsaturated fatty acid and high saturated fatty acid diet respectively. After 3 weeks, all rats were assigned to basic diet for two weeks, then rats from A group were randomly divided into A1 and A2 subgroups. A1 subgroup was fed on basic diet continuously. A2 subgroup and B, C and D groups were assigned to high-fat diet for six weeks. Eight rats from each group were sacrificed at the end of different treatments to detect body weight, body fat content and blood glucose level. RT-PCR was used to determine the gene expression of hormone-sensitive lipase in white adipose tissue. RESULTS: Body weight, body fat content and blood glucose level in C group were significantly lower than those in A2 subgroup on 11 weeks (P < 0.05). The body weight, body fat content in B2 group were significantly lower than those in A2 subgroup (P < 0.05), but blood glucose level was higher than A2 subgroup on 11 weeks (P > 0.05). The body weight in D group was significantly lower than that in A2 subgroup (P < 0.05), but body fat content and blood glucose level were not significantly lower than A2 subgroup on 11 weeks (P > 0.05). The expression of HSL in B2 and C group was higher on 9 weeks and 11 weeks respectively. The HSL mRNA levels in all groups on 3 weeks were similar to that on 11 weeks. CONCLUSION: Feeding on high unsaturated-fatty acid diet after weaning may significantly reduce the body weight, body fat content, improve the abnormal blood glucose level in rats induced by high-fat diet. It was suggested that the high unsaturated-fatty acid diet can be reasonable for weaned rats and gene expression regulation may be involved in programming later obesity by early nutrition.

Adipose Tissue↗
PubMed2006

Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: a meta-analysis.

BACKGROUND: For more than 20 years, tamoxifen has been the mainstay of adjuvant endocrine therapy for women with hormone-sensitive early-stage breast cancer. However, not only does tamoxifen have potential side-effects such as an increased risk of endometrial cancer and thromboembolic events, but patients can also develop resistance to the drug. We aimed to investigate whether switching treatment of postmenopausal women with such breast cancer to anastrozole after 2-3 years of tamoxifen would be more effective than continuing on tamoxifen for a total of 5 years. METHODS: We did a meta-analysis of three clinical trials--the Austrian Breast and Colorectal Cancer Study Group (ABCSG 8), Arimidex-Nolvadex (ARNO 95), and the Italian Tamoxifen Anastrozole (ITA) studies--in which postmenopausal women with histologically confirmed, hormone-sensitive early-stage breast cancer were randomised to 1 mg/day anastrozole (n=2009) after 2-3 years of tamoxifen treatment or to continued 20 or 30 mg/day tamoxifen (n=1997). We analysed the data with a stratified Cox proportional hazards model with the covariates of age, tumour size, nodal status, grade, surgery, and chemotherapy. FINDINGS: Patients who switched to anastrozole had fewer disease recurrences (92 vs 159) and deaths (66 vs 90) than did those who remained on tamoxifen, resulting in significant improvements in disease-free survival (hazard ratio 0.59 [95% CI 0.48-0.74]; p<0.0001), event-free survival (0.55 [0.42-0.71]; p<0.0001), distant recurrence-free survival (0.61 [0.45-0.83]; p=0.002), and overall survival (0.71 [0.52-0.98]; p=0.04). INTERPRETATION: Our results show that the clinical benefits in terms of event-free survival seen in individual trials for those patients who switched to anastrozole translate into a benefit in overall survival. These findings confirm that clinicians should consider switching postmenopausal women who have taken adjuvant tamoxifen for 2-3 years to anastrozole.

Anastrozole↗
PubMed1991

Cholesterol ester hydrolysis and hormone-sensitive lipase in lactating rat mammary tissue.

Neutral cholesterol esterase activity is expressed in extracts of mammary epithelial cells. The identity of the enzyme catalyzing this hydrolysis was investigated. Anti-hormone-sensitive lipase immunoglobulin elicited the total inhibition of this activity and also immunoprecipitated a single phosphoprotein of Mr 84 kDa from mammary cell extracts previously phosphorylated in vitro with [gamma-32P]ATP and cyclic AMP-dependent protein kinase. It is concluded that mammary cell cholesterol esterase activity results from the presence of hormone-sensitive lipase.

Adenosine Triphosphate↗
PubMed1977

Activation of hormone-sensitive lipase and phosphorylase kinase by purified cyclic GMP-dependent protein kinase.

Cyclic GMP-dependent protein kinase, purified to homogeneity from bovine lung, was shown to activate hormone-sensitive lipase partially purified from chicken adipose tissue. The degree of activation was the same as that effected by cyclic AMP-dependent protein kinase although higher concentrations of the cyclic GMP-dependent enzyme were required (relative activities expressed in terms of histone H2b phosphorylation units). Activation by cyclic AMP-dependent protein kinase was completely blocked by the heat-stable protein kinase inhibitor protein from skeletal muscle but activation by the cyclic GMP enzyme was not inhibited. Lipase fully activated by cyclic AMP-dependent protein kinase showed no further change in activity when treated with cyclic GMP-dependent protein kinase. Lipase activated by cyclic GMP-dependent protein kinase was reversibly deactivated by purified phosphorylase phosphatase (from bovine heart); full activity was restored by reincubation with cyclic GMP and cyclic GMP-dependent protein kinase. Cholesterol esterase activity in the chicken adipose tissue fraction, previously shown to be activated along with the triglyceride lipase by cyclic AMP-dependent protein kinase, was also activated by cyclic GMP-dependent protein kinase. Crude preparations of hormone-sensitive triglyceride lipase from human or rat adipose tissue and cholesterol esterase from rat adrenal were also activated by cyclic GMP-dependent protein kinase. Purified phosphorylase kinase (rabbit skeletal muscle) was also shown to be activated by cyclic GMP-dependent protein kinase. The present results, together with those of other workers on histone phosphorylation, suggest that the substrate specificities of cyclic GMP-dependent and cyclic AMP-dependent protein kinase may be similar. This is discussed in the light of a model recently proposed with regard to the relationship between the subunit structures of the two kinases. The physiologic significance of the findings remains to be established.

Adipose Tissue↗
PubMed2002

[The hormone-sensitive adenylyl cyclase system of the ciliate Dileptus anser].

The hormone-sensitive adenylyl cyclase system (AC system) was found and characterized for unicellular eukaryotes--the ciliatae Dileptus anser. It has been first shown that hormones of higher eukaryotes--biogenic amines (adrenalin, isoproterenol and serotonin) and peptide glucagon--stimulate in dose-dependent manner the activity of adenylyl cyclase (AC) of D. anser. The enzymatic activity was stimulated also by guanine nucleotides--GTP and their non-hydrolysable analogue Gpp[NH]p. Stimulating effects of hormones and guanine nucleotides strongly depend on the level of AC basal activity, which is relatively easy to reach (1430 to 3900 pmol cAMP/min per 1 mg of protein). The sensitivity of D. anser AC system to hormones and guanine nucleotides shows the presence of receptor or receptor-related molecules, capable of interacting with the hormone and activating AC through heterotrimeric G-proteins, in ciliatae. On the base of obtained data, a conclusion is made about the similarity of the structural-functional organization of AC systems of D. anser and higher eukaryotes.

Adenylyl Cyclases↗
PubMed1989

Rapid purification of detergent-solubilized bovine hormone-sensitive lipase by high performance hydrophobic interaction chromatography.

Hormone-sensitive lipase (HSL), the enzyme controlling the rate of adipose tissue lipolysis and also possibly involved in the regulation of steroidogenesis, has been purified from bovine omental adipose tissue. Partially detergent-solubilized, delipidated and purified HSL was obtained through step-elution at conventional DEAE ion-exchange chromatography, followed by concentration on hydroxylapatite. High performance hydrophobic interaction chromatography (HPHIC) on phenylsilica then resulted in an increase of HSL protein purity from 2% to more than 70%. Final purification of the enzyme to apparent homogeneity (greater than 95% protein purity), concentration and removal of most of the detergent was obtained by high performance cation exchange chromatography on Mono S. At least 0.5 mg of highly stable HSL was obtained from 5 kg of bovine omental fat within four working days. The purified lipase had a lower specific activity than previously reported for the corresponding rat enzyme but the preparations have proved very useful for enzyme structure studies and as an antigen.

Adipose Tissue↗
PubMed2004

Carbazates as potent inhibitors of hormone-sensitive lipase.

The central role of adipose tissue hormone-sensitive lipase in regulating fatty acid metabolism makes it a potential pharmacological target for the prevention of peripheral insulin resistance in obese, prediabetic and diabetic individuals. The synthesis of a new series of carbazates is presented. Modification of the phenolic 4-position in a series of 1,2,3,4-tetrahydroisoquinoline and morpholine derived carbazates, yielded inhibitors of the catalytic activity of this enzyme with nanomolar potency.

Enzyme Inhibitors↗
PubMed2006

Regulation of hormone-sensitive lipase in islets.

An unique isoform of hormone-sensitive lipase (HSL) is expressed in beta-cells. Recent findings suggest that HSL could be involved in the regulation of glucose stimulated insulin secretion (GSIS), however, these findings are controversial. To test the hypothesis that HSL is involved in control of normal GSIS via changes in its expression and/or activity in response to stimuli, we examined the effects of free fatty acid (FFA) loading and glucagon like peptide-1 (GLP-1) stimulation on the regulation of HSL expression and activity. With prolonged FFA loading, there was increased expression of beta-cell HSL and increased HSL hydrolytic activity in clonal beta-cells. Short-term treatment with GLP-1 increased HSL activity without changing the expression of the beta-cell isoform of HSL. Basal insulin secretion was increased, whereas GLP-1 potentiation of GSIS was decreased in islets isolated from HSL-/- mice, as compared to islets from wild type mice. Furthermore, using PancChip 2.2 cDNA microarrays (NIDDK consortium), the gene expression profile in the islets of HSL-/- mice was compared with wild type mice. Results showed changes in several metabolic pathways due to changes in lipid homeostasis caused by inactivation of HSL. Quantitative PCR for selected genes also revealed changes in genes that are related to insulin secretion, such as UCP-2. Therefore, these results suggest that the beta-cell isoform of HSL is involved in maintaining lipid homeostasis in islets and contributes to the proper control of GSIS.

Animals↗
PubMed1999

Interaction of rat hormone-sensitive lipase with adipocyte lipid-binding protein.

Hormone-sensitive lipase (HSL) is a cytosolic neutral lipase that functions as the rate-limiting enzyme for the mobilization of free fatty acids in adipose tissue. By using the yeast two-hybrid system to examine the potential interaction of HSL with other cellular proteins, evidence is provided to demonstrate a direct interaction of HSL with adipocyte lipid-binding protein (ALBP), a member of the family of intracellular lipid-binding proteins that binds fatty acids, retinoids, and other hydrophobic ligands. The interaction was demonstrated in vitro by the binding of ALBP to HSL translated in vitro, to HSL in extracts of HSL overexpressing Chinese hamster ovary (CHO) cells, and to HSL in extracts of rat adipose tissue. Finally, the presence of ALBP was documented in immune complexes from rat adipose tissue immunoprecipitated with anti-HSL antibodies. The HSL-ALBP interaction was mapped to an N-terminal 300-aa region of HSL that is distinct from the C-terminal catalytic domain. These results suggest that HSL-derived fatty acids are bound by ALBP to facilitate intracellular trafficking of hydrophobic lipids.

Amino Acid Sequence↗
PubMed2000

Analysis of the psychrotolerant property of hormone-sensitive lipase through site-directed mutagenesis.

Mammalian hormone-sensitive lipase (HSL) has given its name to a family of primarily prokaryotic proteins which are structurally related to type B carboxylesterases. In many of these alpha/beta hydrolases, a conserved HG-dipeptide flanks the catalytic pocket. In HSL this dipeptide is followed by two additional glycine residues. Through site-directed mutagenesis, we have investigated the importance of this motif for enzyme activity. Since the presence of multiple glycine residues in a critical region could contribute to cold adaptation by providing local flexibility, we studied the effect of mutating these residues on the psychrotolerant property of HSL. Any double mutation rendered the enzyme completely inactive, without any major effect on the enzyme stability. The partially active single mutants retained the same proportion of activity at reduced temperatures as the wild-type enzyme. These results do not support a role for the HGGG motif in catalysis at low temperatures, but provide further validation of the current three-dimensional model of HSL. Rat HSL was found to be relatively more active than human HSL at low temperatures. This difference was, however, not due to the 12 amino acids which are present in the regulatory module of the rat enzyme but absent in human HSL.

Amino Acid Sequence↗