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 145 records · Page 8Linked to original sources
PubMed1999

Addition of fat to the diets of lactating sows: II. Effects on hormone-sensitive lipase activity, energy mobilization in response to epinephrine, and plasma insulin and glucose concentrations.

Four experiments were conducted to determine the effects of dietary fat on lipolysis in lactating sows. In Exp. 1, a 6 x 6 Latin square was used to determine the optimal dosage of epinephrine for use in a subsequent epinephrine challenge. Peak concentrations of plasma glucose and response area increased linearly (P < .10) with epinephrine dosage. However, plasma NEFA peak and response area were quadratically affected (P < .05 and .06, respectively) by epinephrine dosage, with a minimum NEFA peak concentration observed at .4 microg/kg and a maximum at 1.6 microg/kg. In Exp. 2, the effect of dietary tallow on the response to epinephrine infusion (1.6 microg/kg BW) was examined. No differences (P > .10) between treatments were observed in NEFA, glycerol, or peak concentrations of plasma glucose following epinephrine administration. In Exp. 3, the effect of dietary fat on hormone-sensitive lipase activity was examined. Sows (n = 36) were fed diets containing either 0 or 10% added tallow. Hormone-sensitive lipase activity on d 28 of lactation was increased by the addition of tallow to the diet (P = .06). No effect of dietary tallow was observed on hormone-sensitive lipase activity of adipose tissue on d 21 of lactation (P > .10) in Exp. 3 (n = 16 sows) and Exp. 4 (n = 30 sows). In summary, diets containing 10% added tallow did not alter the rate of lipolysis, as measured by exogenous epinephrine challenge, in adipose tissue of lactating sows.

Animal Nutritional Physiological Phenomena↗
PubMed1997

Adipose tissue lipolysis and hormone-sensitive lipase expression during very-low-calorie diet in obese female identical twins.

Eight pairs of obese female monozygotic twins were subjected to a 4-week, very-low-calorie diet (VLCD) that induced a decrease in mean body mass index from 32.9 +/- 1.1 to 29.7 +/- 1.1 kg/m2. Infusion of the beta-adrenergic agonist, isoproterenol, induced an increase in plasma levels of nonesterified fatty acids and glycerol that was more pronounced during than before VLCD. sc fat biopsies were obtained before and during VLCD to study adipocyte lipolysis. beta-adrenergic sensitivity was moderately improved during VLCD. Basal and stimulated lipolyses, and hormone-sensitive lipase activity and protein levels were increased during VLCD. Before VLCD, intrapair resemblance was found for basal and stimulated lipolysis rates. In response to the treatment, intrapair resemblance was observed for basal lipolysis and for lipolysis stimulated with agents acting on plasma membrane receptors. These results suggest that the increase of basal lipolysis during VLCD is caused by an increase of hormone-sensitive lipase expression. They support the notion that the genotype may play a role in regulating the changes of adipose tissue lipolysis rates observed during VLCD.

Adipose Tissue↗
PubMed2000

Inhibition of adipocyte lipolysis by papaverine: papaverine can inhibit the redistribution of hormone-sensitive lipase.

Papaverine, despite being a potent phosphodiesterase inhibitor, actually blocks adipocyte lipolysis. The present study was designed to clarify the mechanism of the inhibitory effect of papaverine on lipolysis. Lipolysis, stimulated by either 10 microM isoproterenol or 5 mM dibutyryl cAMP, was significantly inhibited by papaverine (100 microM and above). Papaverine, however, did not affect the isoproterenol-induced increase in the protein kinase A (A-kinase) activity ratio. In cell-free extract from non-stimulated adipocytes, cAMP-stimulated A-kinase activities were almost completely blocked by H-89, a potent inhibitor of A-kinase, but not by papaverine. Thus, the inhibitory effect of papaverine on lipolysis could be responsible for a deficit in step(s) distal to A-kinase activity. Hormone-sensitive lipase activities in the infranatant fraction of centrifuged homogenates of cells, which were maximally stimulated with isoproterenol were significantly reduced. This result indicates that hormone-sensitive lipase redistributes from cytosol to its substrate in lipolytically stimulated cells. Papaverine completely blocked the isoproterenol-induced decrease in lipase activity in the infranatant fraction. These results suggest that papaverine blocks lipolysis through its inhibitory effect on the redistribution of hormone-sensitive lipase.

Adipocytes↗
PubMed1987

Multiple effects of phorbol esters on hormone-sensitive adenylate cyclase activity in S49 lymphoma cells.

In S49 lymphoma cells, 12-O-tetradecanoyl phorbol-13-acetate (TPA) enhances adenylate cyclase activity and doubles cAMP accumulation in response to beta-adrenergic stimulation at 37 degrees C, putatively via the action of protein kinase C. At 27 degrees C, TPA has the opposite effect, inhibiting cAMP production in response to isoproterenol by approximately 25%. TPA also inhibits the response to prostaglandin E1 (PGE1), another stimulant of hormone-sensitive adenylate cyclase in these cells, by 30% at 37 degrees C and almost 50% at 27 degrees C. In contrast, TPA enhances responses to forskolin and cholera toxin at both 27 and 37 degrees C. In membranes from cells treated with TPA, PGE1-stimulated adenylate cyclase activity is inhibited by 50%, whereas the catalytic activity stimulated by NaF or forskolin is enhanced. TPA reduces the potency of both PGE1 and isoproterenol for cAMP generation by 50%. TPA causes a similar decrease in beta-adrenergic agonist affinity with no reduction in the density of either antagonist or agonist binding sites in wild type cells and in cells lacking the alpha-subunit of the stimulatory transducer protein (Gs) (cyc-) or lacking functional receptor Gs coupling (UNC). Therefore, TPA has at least three functionally distinct effects on hormone-sensitive adenylate cyclase in S49 cells: a 50% reduction in agonist affinity, attenuation of receptor-transducer coupling, and enhancement of GTP-dependent catalytic activity. We conclude that multiple and opposing effects of TPA on hormone-sensitive adenylate cyclase occur simultaneously within the same cell, affecting the responses to several agonists differently.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1994

Essential differences in cholesteryl ester metabolism between human monocyte-derived and J774 macrophages. Evidence against the presence of hormone-sensitive lipase in human macrophages.

Cholesteryl ester-laden macrophages are the hallmark of the fatty streaks that precede arteriosclerotic plaques in humans and experimental animals. This article studies several aspects of cytoplasmic cholesteryl ester metabolism in cultured human monocyte-derived macrophages. Adenosine 3',5'-cyclic monophosphate (cAMP) consistently inhibited cholesteryl ester mobilization from cells that had been loaded with cholesteryl esters by preincubation with acetylated low-density lipoprotein. This effect was observed in both the absence and presence of extracellular cholesterol acceptors as well as with acyl coenzyme A: cholesterol acyltransferase inhibitors. In contrast, dibutyryl cAMP activated cholesteryl ester hydrolysis in J774 macrophages. Since hormone-sensitive lipase is thought to be responsible for the neutral cholesteryl ester hydrolytic activity in several cell types, we looked for the presence of its mRNA in our macrophages by means of reverse transcription coupled to the polymerase chain reaction technique. Hormone-sensitive lipase mRNA was detected in J774 macrophages but not in human monocytes or in human monocyte-derived macrophages. These results demonstrated great differences in cholesteryl ester metabolism between macrophages of different origin. While hormone-sensitive lipase may be responsible for neutral cholesteryl ester hydrolytic activity in J774 macrophages, in human monocyte-derived macrophages it is not; thus, a different and as yet unidentified enzyme must be present.

Base Sequence↗
PubMed1980

Hormone-sensitive lipase of rat adipose tissue: correlation of activity with a protein of molecular weight 84 000.

Hormone-sensitive lipase of rat adipose tissue was partially purified. The enzyme retained its capacity to be activated by cyclic AMP-dependent protein kinase throughout purification. When the partially purified 32P-labeled preparation was subjected to two-dimensional gel electrophoresis, the enzyme activity was found to be associated with a 32P-labeled protein of molecular weight 84 000. The result suggests that this 32P-labeled protein represents hormone-sensitive lipase or the catalytic subunit of the enzyme.

Adipose Tissue↗
PubMed2000

Regulation of lipoprotein lipase and hormone-sensitive lipase activity and gene expression in adipose and muscle tissue by growth hormone treatment during weight loss in obese patients.

It is well known that growth hormone (GH) treatment reduces fat mass (FM), which presumably is mediated through stimulation of triglyceride breakdown and inhibition of adipose tissue lipoprotein lipase activity (AT-LPL). However, it is unknown which of the 2 GH-regulated pathways are of most importance for the reduction in FM. We investigated the effect of weight loss together with GH treatment on the activity and gene expression of LPL and hormone-sensitive lipase (HSL) in AT and muscle tissue. A very-low-calorie diet ([VLCD] 740 kcal/d) was given to 18 obese women (body mass index [BMI] > 35 kg/m2) and half of them were treated with GH (0.04 IU/kg) for 4 weeks in a randomized double-blind placebo-controlled study. Subcutaneous fat and muscle biopsies were taken before and after 4 weeks. Weight loss after 4 weeks was similar in the 2 groups, with a reduction of 4.5% (placebo) and 4.6% (GH) and a reduction of FM by 7.4% and 9.0% ([NS] nonsignificant). The weight loss resulted in a small and NS reduction of AT-LPL activity by 20% +/- 12% in the placebo group, but in the GH group, AT-LPL was significantly reduced by 65% +/- 8% (P < .01). Muscle LPL (M-LPL) activity was not affected by the weight loss alone, but a significant reduction was observed in the GH group (20.4% +/- 10%, P < .05). AT-HSL activity was significantly enhanced after weight loss, but GH had no additional effect on this minor increment. This is in accordance with the finding that the increment in free fatty acid (FFA) after weight loss was similar in the 2 groups. GH treatment was associated with a significant reduction of high-density lipoprotein (HDL) cholesterol (P < .05). In conclusion, GH significantly inhibited AT-LPL activity but had no additional effect on the hypocaloric-induced loss of FM, indicating that under such circumstances, AT-LPL does not directly regulate adipose tissue mass. GH was not found to have opposite effects on the activity of LPL in adipose tissue and muscle, since GH treatment reduced them both (by 65% and 20%, respectively). The VLCD-induced weight loss was associated with a minor enhanced activity of AT-HSL with no independent effect of GH. Thus, concerning body weight, FM, and lipolytic activity, treatment with GH offers no extra benefits during a VLCD for 4 weeks.

Adipose Tissue↗
PubMed1976

Lipoprotein lipase and hormone-sensitive lipase activities in human subcutaneous lipomas: comparison with normal subcutaneous adipose tissue.

1. Lipoprotein lipase activity and hormone-sensitive lipase activity were investigated in subcutaneous lipomas removed from two patients and compared with the enzyme activities in subcutaneous adipose tissue from two normal subjects. 2. Confirmation was obtained of the presence of lipoprotein lipase activity in lipomas with an activity fifteen to forty-five times that in the two control samples. 3. Hormone-sensitive lipase activity was demonstrated in lipomas under basal conditions of assay as well as in the presence of adrenaline plus theophylline. However, compared with the non-lipomatous fat samples, these activities were lower, as was the magnitude of the lipolytic response to adrenaline plus theophylline. 4. The significance of these measurements of enzyme activity and their role in the pathogenesis of lipomas are briefly discussed.

Adipose Tissue↗
PubMed2004

Different growth hormone sensitivity of target tissues and growth hormone response to glucose in HIV-infected patients with and without lipodystrophy.

Growth hormone (GH)-secretion in HIV-lipodystrophy is impaired; however, GH-sensitivity of GH-target tissues remains to be evaluated. We measured overnight fasting concentrations of GH-sensitive insulin-like growth-factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) including GH binding protein (GHBP), a marker of GH-receptor sensitivity, in antiretroviral treated HIV-infected patients with (LIPO) and without lipodystrophy (NONLIPO) and antiretroviral naive HIV-infected patients (NAIVE). Three h GH-suppression tests using oral glucose were undertaken to determine dynamics of GH-secretion. IGF-I and IGFBP-3 were increased in LIPO compared with NONLIPO (p <0.05), but did not differ significantly between NONLIPO and NAIVE. Area under the curve of GH (AUC-GH) during the GH-suppression test was decreased in LIPO compared with NONLIPO (p <0.05). Ratio of limb to trunk fat, which was decreased in LIPO compared to NONLIPO and NAIVE (p <0.001), correlated positively with AUC-GH and rebound-GH (p <0.05). All groups displayed suppression of GH during the suppression test (p <0.05) and all groups, except LIPO, displayed a rebound of GH (p <0.05), which probably is explained by persistently increased plasma glucose in LIPO compared with NONLIPO and NAIVE (p <0.01). GHBP was inversely correlated with AUC-GH (p <0.01). Our data suggest that GH-target tissues in LIPO are at least as GH-sensitive as in HIV-infected patients without lipodystrophy.

Absorptiometry, Photon↗
PubMed1992

Initiation and maintenance of in vitro decidualization are independent of hormonal sensitization in vivo.

The effects of in vivo hormonal sensitization on the competence of uterine stromal (US) cells to decidualize in vitro were assessed. In vitro differentiation of uterine stroma isolated from Day 4 pregnant rats, sensitized to respond to a decidual stimulus, was compared to that in nonsensitized immature, castrated or cycling rats. The initiation of in vitro decidualization--as monitored by the expression of the decidual markers desmin and laminin in rat US cells--was independent of the hormonal status of the animal from which the cells were isolated and occurred in the absence of serum in the medium. Differentiation was accelerated in high-density cultures where contact inhibition suppressed proliferation and decreased the extent of cell growth. The extent to which in vitro decidualization imitates in vivo stromal cell differentiation was assessed by comparing decidualization in the rabbit, a species with only a limited decidual cell response, and in the rat. US cells isolated from nonpregnant rabbits differentiated in vitro by expressing laminin, but not desmin. Indirect immunofluorescence of frozen uterine sections from pregnant and nonpregnant rabbits validated in vitro differentiation as a faithful reflection of the in vivo program of decidualization. Although the program of US cell differentiation may vary between the species, initiation of differentiation in vitro appeared to be independent of hormonal preparation in vivo for both the species examined.

Animals↗
PubMed1990

Regulation of bovine adipose tissue metabolism during lactation. 6. Cellularity and hormone-sensitive lipase activity as affected by genetic merit and energy intake.

Subcutaneous adipose tissue cell size and density and hormone-sensitive lipase activity were determined during late pregnancy and first lactation in Holstein heifers. Animals were daughters of bulls with either +791 (high line) or +390 (low line) kg Predicted Difference (1974 base) for milk. Each line consumed either a 71%: 29% (high energy) or a 36%:63% (low energy) barley concentrate and alfalfa hay diet from 0 to 140 d lactation. Heifers fed the low energy ration ate 33% less NE1 and produced 20% less milk with 52.7% greater milk fat percentage during 28 to 140 d of lactation than heifers fed the high energy ration. Prepartum, animals of the high line had similar adipocyte volume and density to low line animals. However, during early lactation, high line animals had a greater decrease in volume and a larger increase in density than low line animals. There was a delayed recovery of volume in high line, compared with low line animals in late lactation. Adipocyte volume also was decreased by dietary energy restriction. Hormone-sensitive lipase activity was similar in both genetic lines prepartum and increased in all groups at 60 d postpartum. Animals of high line or fed low energy rations had increased activity per gram during early, but not later, lactation. Activity per cell and per milligram cytoplasm protein increased in all groups in early lactation and were highest in high line animals fed the low energy ration.

Adipose Tissue↗
PubMed2004

Regulation and role of hormone-sensitive lipase activity in human skeletal muscle.

Hormone-sensitive lipase (HSL) is believed to play a regulatory role in initiating the degradation of intramuscular triacylglycerol (IMTG) in skeletal muscle. A series of studies designed to characterise the response of HSL to three stimuli: exercise of varying intensities and durations; adrenaline infusions; altered fuel supply have recently been conducted in human skeletal muscle. In an attempt to understand the regulation of HSL activity the changes in the putative intramuscular and hormonal regulators of the enzyme have also been measured. In human skeletal muscle at rest there is a high constitutive level of HSL activity, which is not a function of biopsy freezing. The combination of low adrenaline and Ca(2+) levels and resting levels of insulin appear to dictate the level of HSL activity at rest. During the initial minute of low and moderate aerobic exercise HSL is activated by contractions in the apparent absence of increases in circulating adrenaline. During intense aerobic exercise, adrenaline may contribute to the early activation of HSL. The contraction-induced activation may be related to increased Ca(2+) and/or other unknown intramuscular activators. As low- and moderate-intensity exercise continues beyond a few minutes, activation by adrenaline through the cAMP cascade may also occur. With prolonged moderate-intensity exercise beyond 1-2 h and sustained high-intensity exercise, HSL activity decreases despite continuing increases in adrenaline, possibly as a result of increasing accumulations of free AMP, activation of AMP kinase and phosphorylation of inhibitory sites on HSL. The existing work in human skeletal muscle also suggests that there are numerous levels of control involved in the regulation of IMTG degradation, with control points downstream from HSL also being important. For example, it must be remembered that the actual flux (IMTG degradation) through HSL may be allosterically inhibited during prolonged exercise as a result of the accumulation of long-chain fatty acyl-CoA.

Enzyme Activation↗
PubMed1992

Mechanism of hormone-stimulated lipolysis in adipocytes: translocation of hormone-sensitive lipase to the lipid storage droplet.

Hormone-sensitive lipase activity (HSL), which is found in the supernatant of centrifuged homogenates of lipolytically quiet isolated rat adipocytes, was greatly reduced in or absent from the supernatant of lipolytically stimulated cells. The lipase was purified 100- to 250-fold from the supernatant of lipolytically quiet cells to 10-20% purity by a single passage over phenyl-Sepharose resin with high (greater than 70%) activity yields. Western blotting of adipocyte homogenate fractions with polyclonal antiserum raised against HSL showed that the enzyme shifted quantitatively from the supernatant of control cells to the floating "fat cake" of lipolytically stimulated cells. A similar shift to the fat cake was observed when cells were disrupted by hypotonic lysis and centrifugation rather than by homogenization. We propose that upon lipolytic activation of adipocytes and phosphorylation of HSL by cAMP-dependent protein kinase, the critical event is not an increase in catalytic activity (i.e., turnover number) but a translocation of the lipase to its substrate at the surface of the lipid storage droplet.

Adipose Tissue↗
PubMed1990

Identification and role of the basal phosphorylation site on hormone-sensitive lipase.

Phosphorylation site 2 on bovine hormone-sensitive lipase (HSL), which is phosphorylated in vitro by the AMP-activated protein kinase, has been found also to be phosphorylated in vitro by glycogen synthase kinase-4. Peptide mapping of HSL phosphorylated in vitro and in isolated adipocytes demonstrates that this site corresponds to the basal phosphorylation site on HSL, which is phosphorylated in intact adipocytes in the absence of lipolytic stimuli. Site 2 has been proposed to have an antilipolytic role in that phosphorylation at this site greatly reduces subsequent phosphorylation (at site 1) and activation of HSL by cyclic-AMP-dependent protein kinase. Further evidence for an antilipolytic role of site 2 has been obtained using a synthetic peptide based on the sequence around sites 1 and 2. Phosphorylation of the peptide at site 2 totally prevents the subsequent phosphorylation of site 1 and vice versa.

Adipose Tissue↗
PubMed1995

Overexpression of hormone-sensitive lipase prevents triglyceride accumulation in adipocytes.

Hormone-sensitive lipase (HSL) is a cytosolic neutral lipase that hydrolyzes intracellular stores of triglycerides within adipocytes and is thought to be the rate limiting enzyme in lipolysis; however, direct evidence to prove this concept has been lacking. The present study was designed to establish the function of HSL in adipocytes. A 2360-bp fragment containing the entire HSL coding region was cloned into the vector pCEP4 and was used to transfect the 3T3-F442A adipogenic cell line. Nondifferentiated, transfected cells were screened for HSL overexpression by indirect immunofluorescence microscopy and confirmed by immunoblotting cell extracts with anti-HSL/fusion protein antibodies and by Northern blots for HSL mRNA. Stable transfectants overexpressing HSL were obtained and cloned. Compared with undifferentiated 3T3-F442A cells transfected with pCEP4 not containing the insert (vector alone) where HSL expression was very low, undifferentiated HSL transfectants had up to a 100-fold increase in HSL activity. Likewise, immunoreactive HSL protein and HSL mRNA levels were increased up to 100-fold in HSL transfectants. When confluent cells were allowed to differentiate by exposure to insulin, HSL expression increased in vector alone transfected cells, but remained below that observed in HSL transfectants. A similar degree of differentiation was seen in both vector alone and HSL transfectants when based on the induction of lipoprotein lipase. Cellular triglyceride content increased dramatically in the vector alone transfected cells while triglyceride content was markedly reduced in the HSL transfectants. The expression of late markers of adipocyte differentiation, such as aP2 and GPDH, was diminished and appeared to vary with the degree to which HSL was overexpressed and the cellular triglyceride content was reduced. Thus, the overexpression of HSL in 3T3-F442A cells prevents differentiated adipocytes from taking on the appearance of fat cells, i.e., accumulating triglyceride. Furthermore, the overexpression of HSL directly or indirectly attenuates the expression of several genes that appear during late adipocyte differentiation.

3T3 Cells↗
PubMed1987

The regulatory and basal phosphorylation sites of hormone-sensitive lipase are dephosphorylated by protein phosphatase-1, 2A and 2C but not by protein phosphatase-2B.

The activity of hormone-sensitive lipase, the rate-limiting enzyme in adipose tissue lipolysis, is controlled by cAMP-mediated phosphorylation at a specific regulatory phosphorylation site. The lipase is also phosphorylated at a site, termed basal, without any effects on its activity [Strålfors et al. (1984) Proc. Natl Acad. Sci. USA 81, 3317-3321]. The capacity of protein phosphatase-1, 2A, 2B and 2C to dephosphorylate the lipase, selectively phosphorylated by glycogen synthase kinase-4 and cAMP-dependent protein kinase at the basal and regulatory phosphorylation sites, was compared with that towards glycogen phosphorylase and phosphorylase kinase (alpha subunit). Protein phosphatase-1, 2A and 2C were found to dephosphorylate both phosphorylation sites of hormone-sensitive lipase, while protein phosphatase-2B had no measureable activity towards any of the sites. When the activities of protein phosphatase-1, 2A and 2C were normalized with respect to the reference substrates, they were found to dephosphorylate the lipase regulatory site in the approximate relations of 1:4:3 and the basal site in the approximate relations of 1:6:4. Protein phosphatase-1 showed 20% higher and protein phosphatase-2A and 2C 80% higher activity towards the basal site compared to the regulatory site. The two phosphorylation sites of the lipase were comparable to good substrates for protein phosphatase-2A and 2C, but relatively poor substrates for protein phosphatase-1. Protein phosphatase-2C activity towards the lipase was completely dependent on Mg2+ with a half-maximal effect at 3 mM. Protamine increased the lipase dephosphorylation by protein phosphatase-1 3-5-fold with half-maximal effect at 0.6 microgram/ml, and by protein phosphatase-2A about 2-fold with half-maximal effect at 3-5 micrograms/ml, thus illustrating the potential for control of these lipase phosphatase activities.

Adipose Tissue↗
PubMed1976

Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.

The possibility has been explored that decreases of adenylate cyclase may explain diminished hormone sensitivity of adipose tissue with aging. Isolated cells were prepared from epididymal fat pads of rats 1-, 2-, 6-, 12-, and 24-mo old, fixed in OSO4, and sized and counted with a Coulter apparatus. Adenylate cyclase was assayed in cell membranes (ghosts) using [alpha-32P] ATP as substrate and expressed as cyclic [32P] AMP/10 min per mg protein or per 10(6) cells. Enzyme activity was determined for the basal state and in the presence of varying concentrations of glucagon, ACTH, epinephrine, and fluoride. Basal activity per cell increased in threefold between 1 and 2 mo with a comparable increase in cell surface area, suggesting synthesis of enzyme along with new cell membrane. Although epinephrine stimulated adenylate cyclase 8-fold and fluoride 12-fold throughout the life-span of the rat, stimulated activity paralleled basal levels, decreasing 60% between 2 and 24 mo per mg protein and 40% between 6 and 24 mo per cell. Glucagon stimulated adenylate cyclase 4.5-fold relative to basal in the 1-mo-old rat, but its effect then rapidly decreased and was absent by 12 mo. The fourfold stimulation by ACTH noted in the 1-mo-old animals decreased gradually with age but was still twice basal at 24 mo. Since no significant change of cell size occurred after 6 mo, diminished hormone sensitivity with senescence cannot be related to cell size. Similar age-related patterns of hormonal activation were evoked by 5'-guanylyl-imidodiphosphate [GMP-P(NH)P], a nucleotide analogue which increased both basal- and hormone-activated enzyme at all ages studied. Dose-response curves to hormones, fluoride, and GMP-P (NH)P were not affected by age. High Mg++ (50 mM) in the presence of GMP-P-(NH)P stimulated adenylate cyclase to levels greater than with fluoride, but a similar loss of activity with aging was still observed. Loss of hormone receptors may partially explain the age-related decreases of glucagon and ACTH-sensitive adenylate cyclase, but decreased basal-, epinephrine-, fluoride-, and GMP-P-(NH) P-stimulated responses suggest loss of the catalytic component of the adenylate cyclase enzyme complex in the aging fat cell membranes.

Adenylyl Cyclases↗
PubMed1986

[Adenylate cyclase complex, lipids and the regulation of the hormonal sensitivity of tumor tissue].

This review consists of the following parts: plasma membranes of cells in normal and cancer tissue; adenylate cyclase complex (ACC) and tumour development; ACC regulation and phase state of lipids in the membranes of tumour cells; interrelations of ACC with the other signal-receiving systems of normal and tumour cells; the role of ACC in providing, changing and analyzing the hormone sensitivity of tumour tissue, regulation of the hormone sensitivity of tumour tissue by means of influences on ACC.

Adenylyl Cyclases↗