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Biomedical subjects

V Hansson

Publications and source records attributed to V Hansson.

At least 127 records · Page 7Linked to original sources
PubMed1985

Beta-adrenoceptor density and relative number of beta-adrenoceptor subtypes in biopsies from human right atrial, left ventricular, and right ventricular myocard.

In the present study we estimated the relative number of beta-adrenoceptors in membrane preparations from right atrial and left ventricular biopsies from 8 patients, as well as from right ventricular biopsy from one patient. Determinations of relative number of beta adrenoceptor subtypes (beta1, beta2) were also performed. Estimations were performed in a radioligand assay, measuring specific binding of [125I]-cyanopindolol (CYP). Inhibition of specific [125I] CYP binding was studied by adding propranolol (non-selective antagonist), atenolol (beta1 selective antagonist) and ICI 118551 (beta2 selective antagonist) to the preparations. Some individual variance in total number of receptors was found. Per mg protein, the number of binding sites were higher in atrial preparations (mean 71.4 +/- 14.4 fmol X mg-1) than in left ventricular preparations (mean 30.2 +/- 7.1 fmol X mg-1). Receptor number in the right ventricular preparation was 49.5 +/- 2.6 fmol X mg-1. Approximately 25% of beta adrenoceptors were of beta2 subtype in preparations from both right atrial and left ventricular biopsies, as well as from the right ventricular biopsy. Thus, there are regional differences in the quantity of beta adrenoceptors in human myocard whereas the relative proportion of beta1 and beta2 receptors appears to be fairly constant.

Biopsy↗
PubMed1985

Hypertrophic cardiomyopathy characterised by beta-adrenoceptor density, relative amount of beta-adrenoceptor subtypes and adenylate cyclase activity.

The total quantity of beta-adrenoceptors and the relative amount of beta 1 and beta 2 receptor subtypes were determined in heart biopsies of 10 patients with various heart diseases and 5 patients suffering from hypertrophic cardiomyopathy (HOCM). In membrane particle preparations from the same patients we also examined the activity of the adenylate cyclase (AC), and its response to isoprenaline, terbutaline, histamine and sodium fluoride (NaF). The high affinity ligand [125I] (1)-cyanopindolol (CYP) was used in the binding assays, and the highly beta 2-selective antagonist ICI 118 551 for the determination of beta-adrenoceptor subtypes. No differences were found in total beta-adrenoceptor density between patients with HOCM and "controls" (27.6 +/- 14.2 vs 26.5 +/- 10.7 fmol . mg-1 protein). The relative amounts of beta 1 and beta 2 receptor subtypes were similar, patients with HOCM had 82.1 +/- 4.9% of beta 1 and 14.4 +/- 3.9% of the beta 2 receptor subtype, compared with 76.3 +/- 11.5% of beta 1 and 20.7 +/- 11.0% of the beta 2 subtype in the "control" patients. Both absolute activity of AC (pmol . mg-1 protein . min) as well as the relative responses to the various stimulators were not significantly different between the two groups. Thus, this study does not support the hypothesis that HOCM is a disorder with altered beta-adrenoceptor number or adenylate cyclase response to adrenergic agonists. Furthermore, HOCM is not associated with altered response of the AC system to histamine or NaF.

Adenylyl Cyclases↗
PubMed1985

Studies on the mechanism of follicle-stimulating hormone-induced desensitization of Sertoli cell adenylyl cyclase in vitro.

When Sertoli cells were cultured in the presence of follicle-stimulating hormone (FSH), a time-and concentration-dependent desensitization of FSH-responsive adenylyl cyclase (AC) was observed. Maximal desensitization (80%) was attained after 6-9 h of incubation with FSH (10 micrograms/ml; NIH-FSH-S12). During 24 h of incubation the concentration of FSH causing a half-maximal desensitization was about 100 ng/ml. Removal of the hormone from the culture medium was associated with a gradual reappearance of the FSH response. Follicle-stimulating hormone-induced desensitization of Sertoli cell AC was specific for homologous hormone, since AC activation by isoproterenol was unaffected. Furthermore, AC activity of control and FSH-desensitized cells was equally activated by GTP and fluoride, showing that the interaction of the guanyl nucleotide regulatory (N) component with the catalytic subunit is not affected during FSH-induced desensitization. A loss in specific FSH binding was detected after 9 and 24 h of exposure to FSH, but not at shorter times of incubation. Desensitization of Sertoli cell AC to both FSH and isoproterenol stimulation could also be achieved by dibutyryl cyclic AMP (dbcAMP); however, a 30-40% desensitization required a high nucleotide concentration (1 mM) and a long incubation time (24 h). These results show that desensitization of Sertoli cell AC by FSH is associated with normal function of the N component, and precedes any significant loss in specific FSH binding sites. Furthermore, exogenous addition of dbcAMP (1 mM) did not cause the same effects on Sertoli cell AC as did FSH.

Adenylyl Cyclases↗
PubMed1985

Effects of adenosine analogs on glucagon-stimulated adenosine 3',5'-monophosphate formation in Sertoli cell cultures from immature rats.

In the present study, we have examined the effects of two adenosine analogs, (-)N6-(R)phenyl-isopropyl-adenosine (PIA) and 2-chloro-adenosine, on glucagon- and FSH-stimulated cAMP production in Sertoli cell cultures isolated from immature (19-day-old) rats. Both FSH and glucagon caused a 5- to 10-fold stimulation of cAMP levels in the spent media from Sertoli cell cultures during an 18-h incubation. Addition of 1 microM PIA significantly inhibited both FSH- and glucagon-stimulated cAMP levels. In the presence of a maximal concentration of glucagon (2.5 micrograms/ml), PIA caused a concentration-dependent inhibition of cAMP formation, and the concentration of PIA causing half-maximal inhibition of cAMP formation (IC50) ranged from 0.5-1 nM. When Sertoli cells were incubated with increasing concentrations of glucagon (1.28 ng/ml to 4.00 micrograms/ml) in the absence and presence of either PIA (1.0 microM) or 2-chloro-adenosine (10.0 microM), the responses to glucagon, measured as cAMP formation, were almost completely abolished. 1-Methyl-3-isobutylxanthine (MIX), a well known inhibitor of cAMP phosphodiesterase activity, is also an inhibitor of adenosine binding to receptors on the cell membrane. When Sertoli cells stimulated with glucagon (2.5 micrograms/ml) were incubated in the absence and presence of MIX (0.1 mM) and increasing concentrations of PIA (0.025-10,000 nM), the presence of MIX reduced the inhibitory activity of PIA by almost 2 orders of magnitude (IC50 without MIX, 0.5 nM; IC50 with MIX, 20 nM). Thus, the present study shows that adenosine analogs inhibit agonist-stimulated cAMP formation in cultured Sertoli cells, and that MIX reduces this effect. This indicates that cultured Sertoli cells from immature rats contain A1-receptors for adenosine mediating inhibitory effects on adenylate cyclase.

2-Chloroadenosine↗
PubMed1985

Metabolism of palmitate in cultured rat Sertoli cells.

Isolated rat Sertoli cells were incubated in the presence of [1-14C]palmitate at a cell concentration of 1.54 +/- 0.31 mg protein/flask (n = 7). The oxidation of palmitate was concentration dependent and maximal oxidation was obtained at 0.35 mM-palmitate. At a saturating concentration of palmitate the oxidation was linear for at least 6 h. About 65% of the total amount of palmitate oxidized during 5 h at 0.52 mM-palmitate (109 +/- 44 nmol/flask, n = 5) was recovered as CO2 and the rest as acid-soluble compounds. Almost all radioactive acid-soluble compounds which were secreted by the Sertoli cells were shown to be 3-hydroxybutyrate and acetoacetate. The palmitate recovery in cellular lipids and triacylglycerols was 9.4 +/- 5.1 nmol/flask (n = 5) and 3.5 +/- 2.8 nmol/flask (n = 5) respectively. Addition of glucose had no significant effect on palmitate oxidation but caused a 9-fold increase in esterification of palmitate into triacylglycerols. We conclude that cultured rat Sertoli cells can oxidize palmitate to CO2 and ketone bodies and that fatty acids appear to be a major energy substrate for these cells.

3-Hydroxybutyric Acid↗
PubMed1985

Seasonal variations of LH, prolactin, androstenedione, testosterone and testicular FSH binding in the male blue fox (Alopex lagopus).

The seasonal changes in testicular weight in the blue fox were associated with considerable variations in plasma concentrations of LH, prolactin, androstenedione and testosterone and in FSH-binding capacity of the testis. An increase in LH secretion and a 5-fold increase in FSH-binding capacity were observed during December and January, as testis weight increased rapidly. LH levels fell during March when testicular weight was maximal. Plasma androgen concentrations reached their peak values in the second half of March (androstenedione: 0.9 +/- 0.1 ng/ml: testosterone: 3.6 +/- 0.6 ng/ml). A small temporary increase in LH was seen in May and June after the breeding season as testicular weight declined rapidly before levels returned to the basal state (0.5-7 ng/ml) that lasted until December. There were clear seasonal variations in the androgenic response of the testis to LH challenge. Plasma prolactin concentrations (2-3 ng/ml) were basal from August until the end of March when levels rose steadily to reach peak values (up to 13 ng/ml) in May and June just before maximum daylength and temperature. The circannual variations in plasma prolactin after castration were indistinguishable from those in intact animals, but LH concentrations were higher than normal for at least 1 year after castration.

Androgens↗
PubMed1985

Physicochemical properties of the soluble Mn2+-dependent adenylate cyclase in the blue fox testis.

Physicochemical properties of the soluble Mn2+-dependent adenylate cyclase (MnAC) in the blue fox testis were examined. MnAC activity in the cytosol fraction (106,000 g) migrated in a linear sucrose gradient as a single peak with a sedimentation coefficient (S20,W) of 4.2 Gel filtration on a Sephadex G-200 column revealed an Einstein-Stokes radius of 28 A and a frictional ratio of 1.15, indicating a molecular weight of approximately 51,000. The MnAC migrated as a single peak of activity during polyacrylamide gel electrophoresis with an Rf of 0.52. The isoelectric point (pI) estimated by isoelectric focusing was 5.5.

Adenylyl Cyclases↗
PubMed1985

Membrane-bound adenylate cyclase activity in the testis of the blue fox.

Membrane-bound adenylate cyclase (AC) activity was much higher in the presence of Mn2+ than of Mg2+. The Mn2+-sensitive adenylate cyclase (MnAC) showed a linear rate of activity for at least 60 min. In contrast, the Mg2+-sensitive AC (MgAC) displayed a considerable burst in activity, so that after 90 min of activity it was approximately tenfold higher than at the start of incubation. Guanine nucleotides enhanced MgAC activity; 10(-6) to 10(-5) M of 5'-guanylylimidodiphosphate caused a threefold stimulation. The MgAC could be stimulated by hormones (FSH, hCG, PGE1, isoproterenol, glucagon), the highest activation being achieved with FSH. Increasing levels of ATP produced a concentration-dependent increase in MgAC activity. The apparent affinity of the AC for MgATP increased threefold (Km 0.50-0.15 mM) by raising the free Mg2+ concentration from 0.4 to 10.0 mM. The membrane-bound AC of the blue fox testis is thus regulated by hormones, Mg2+, and guanine nucleotides in a similar manner to ACs in other somatic cells and in testes from other species. The high MnAC activity in membrane particles from these testes probably represents membrane-bound AC activity in germ cells. The burst in MgAC activity during incubation may represent proteolytic activation of membrane-bound germ cell AC, with a gradual appearance of Mg2+ sensitivity.

Adenylyl Cyclases↗
PubMed1985

Properties and regulation of GnRH receptors in the anterior pituitary and the testis of the rat: different response of Leydig cell LH and GnRH receptors to hormonal treatments.

The properties (association and dissociation rates, affinity and specificity) of GnRH receptors in the rat pituitary and the Leydig cells are very similar. In addition, in vivo administration for 5 or 11 days of 10 micrograms of GnRH to adult rats resulted in an increase (p less than 0.01) in both Leydig cell and pituitary GnRH receptors. In contrast, the same treatment caused a significant decrease (p less than 0.01) of Leydig cell LH receptor number. Furthermore, testosterone propionate (500 micrograms/day), which had no effect on Leydig cell LH receptors, caused a significant increase (p less than 0.01) of testicular GnRH receptors but a decrease (p less than 0.01) of pituitary GnRH receptors. Estradiol 17 beta valerate (5 micrograms/day) reduced (p less than 0.01) both testicular (5 days) and pituitary (5 and 11 days) GnRH receptors. Such treatment for 5 days also decreased (p less than 0.05) the Leydig cell LH receptors. No effect of dexamethasone and 17-hydroxyprogesterone was seen after 5 or 11 days of treatment. Thus, although pituitary and Leydig cell receptors appear similar, their regulation by exogenous hormone treatments is different. Furthermore, the regulation of Leydig cell GnRH and LH receptors also appears very different, suggesting different roles of the receptors in the control of the Leydig cell function.

17-alpha-Hydroxyprogesterone↗
PubMed1984

A transplantable rat Leydig cell tumor--1. LH and prolactin receptors and effects of the endocrine status of the host animal.

We have examined the binding capacity and properties (affinity, specificity) of LH and prolactin (Prl) receptors in a transplantable rat Leydig cell tumor (H-540) grown in intact, castrated and hypophysectomized rats. LH receptors in adult rat testis and Prl receptors in the rat ventral prostate were examined simultaneously for comparison. The results can be summarized as follows: The qualitative properties (affinity, specificity) of LH and Prl receptors in tumor Leydig cells appear to be identical to those of corresponding receptors in non-tumor tissues. The levels of LH receptors in tumor Leydig cells are only some 1% of that present in normal Leydig cells from adult rats. Tumor Leydig cells grown in hypophysectomized rats had even lower levels of LH receptors; ca. 1/3 of that found in tumors from intact rats. The levels of Prl receptors in the tumor Leydig cells are almost as high as in normal Leydig cells from adult rats. In tumors grown in hypophysectomized rats, the levels of Prl receptors were much lower (ca. 20%) than in tumors from intact or castrated rats. There were great variations in the number of LH and Prl receptors in individual tumors, and there was a positive correlation (r = 0.88; P less than 0.01) between LH and Prl receptors in individual tumors. No differentiation toward a "LH receptor tumor" or "Prl receptor tumor" was observed. Thus, receptors for LH and Prl in tumor cells are qualitatively normal, but the number is greatly (LH) or moderately (Prl) reduced. These receptors in the tumor Leydig cells are stimulated by pituitary hormones.

Animals↗
PubMed1984

A transplantable rat Leydig cell tumor--2. Adenylyl cyclase activation by prostaglandin E1, isoproterenol and glucagon.

The responsiveness of the membrane bound adenylyl cyclase (AC) system to various hormones and hormone analogues in a transplantable rat Leydig cell tumor (H-540) has been investigated and compared with that of interstitial tissue from normal adult rats. The results can be summarized as follows: The AC of the Leydig cell tumors was stimulated by isoproterenol, epinephrine, norepinephrine, dopamine, glucagon, PGE1, PGF2 alpha and LH/hCG. The AC of the Leydig cell tumors exhibited a much greater response to PGE1 than the AC in normal interstitial tissue (5-fold and 2-fold stimulation, respectively). The AC of the Leydig cell tumours also revealed a somewhat higher response to isoproterenol than the AC of interstitial tissue (2.5-fold and 2-fold, respectively). Adenylyl cyclase in both tissues were equally stimulated by glucagon (2-fold). The LH response in the Leydig cell tumors was only half of that found in normal Leydig cells. This study indicates, that in spite of the fact that tumor Leydig cells respond to LH and produce testosterone, the response pattern of the AC is different from that of normal Leydig cells.

Adenylyl Cyclases↗
PubMed1984

Beta-adrenergic regulation of Sertoli cell adenylyl cyclase: desensitization by homologous hormone.

Incubation of Sertoli cell-enriched cultures with D,L-isoproterenol caused a time- and concentration-dependent, homologous desensitization of isoproterenol-responsive adenyl cyclase, whereas the response to FSH was unaffected. Half-maximal desensitization was achieved within 1 h of preincubation, after which a more gradual loss of response was observed. Preincubation of Sertoli cells for 24 h with increasing concentrations of D,L-isoproterenol demonstrated that the concentration required to obtain half-maximal densensitization was approximately 10-fold lower than the Km for activation of adenylyl cyclase. The function of the guanine nucleotide regulatory component (N-component) of the adenylyl cyclase complex in hormonally desensitized Sertoli cells, as evaluated by activation of adenylyl cyclase by GTP, GMPP(NH)P, fluoride and Mg2+, was not affected by the hormone pretreatment. Preincubation of Sertoli cells with a high concentration of dbcAMP (10(-3) M) for 24 h was associated with a 45% reduction in adenylyl cyclase activation by both FSH and isoproterenol. Also in this case fluoride- and GTP-stimulated adenylyl cyclase activities were normal. However, the effects of dibutyryl cyclic AMP occurred much more slowly than agonist-induced desensitization, indicating that cAMP may not be the primary mediator of homologous desensitization of Sertoli cell adenylyl cyclase by isoproterenol.

Adenylyl Cyclases↗
PubMed1984

Regulation of hormone-responsive Sertoli cell adenylyl cyclase in a cell-free system.

Homologous desensitization of either FSH- or isoproterenol-responsive adenylyl cyclases in Sertoli cell membranes can be achieved in a cell-free system. Incubation of membrane particles from cultured immature Sertoli cells with either FSH or isoproterenol resulted in a time- and concentration-dependent loss of subsequent adenylyl cyclase response to the homologous hormone. Half-maximal refractoriness was achieved within 20-30 min of incubation. The concentration of FSH required to obtain half-maximal loss of adenylyl cyclase response (400 ng/ml) was in the same order of magnitude as the apparent Km for FSH-stimulated adenylyl cyclase activity (300 ng/ml). Hormone-induced homologous desensitization was dependent on the presence of both ATP and Mg2+. Increasing concentrations of ATP in the presence of FSH caused a concentration-dependent loss of subsequent response to the homologous hormone. Half-maximal desensitization was achieved at an ATP concentration of 0.2 mM. Increasing concentrations of Mg2+ in the presence of either FSH or isoproterenol caused desensitization for the homologous hormone. The concentration of Mg2+ giving half-maximal effect was approximately 5 mM in excess of ATP and EDTA. However, higher concentrations of free Mg2+, in the absence of hormone, caused desensitization of both FSH- and isoproterenol-sensitive adenylyl cyclase with half-maximal effect at approximately 30 mM. Hormone-specific desensitization was obtained in the presence of GTP. However, when GTP was substituted with the non-hydrolysable analogue GMPP(NH)P the hormonal activation remained constant throughout 90 min of incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1984

Changes in isoproterenol-stimulated adenylate cyclase activity in rat testicular tissue during cryptorchidism and after orchidopexy.

Cryptorchidism was associated with increased responsiveness of the isoproterenol-sensitive adenylate cyclase in membrane particles from rat testis. Abdominal testes from uni- and bilaterally cryptorchid rats showed the same activities. The change in isoproterenol-responsive adenylate cyclase was independent of the age at which the animals were made cryptorchid. The isoproterenol response was maximal 3-4 weeks after the rats were made cryptorchid. By 2-3 months after orchidopexy the isoproterenol response in the rat testis had decreased to normal control values.

Adenylyl Cyclases↗
PubMed1984

Seasonal changes in spermatogenesis in the blue fox (Alopex lagopus), quantified by DNA flow cytometry and measurement of soluble Mn2+ -dependent adenylate cyclase activity.

The testes of the blue fox (Alopex lagopus) showed marked seasonal variations in size. Testicular weight and volume increased rapidly during January and February to reach maximal values by the beginning of the breeding season (approximately 15 March). During May and June the weights and volumes of the testes declined gradually to the quiescent state which lasted from July until October. Quantitation by DNA flow cytometry of the seasonal changes in the relative numbers of haploid (1C), diploid (2C) and tetraploid (4C) cell numbers in the testis showed that the increase in testis size from December to February was associated with a rapid expansion of the haploid cell compartment as spermatogenesis resumed. In addition, an increase in number of more mature cell types within the haploid cell population was observed over a 2-month period before the breeding season. The decline in testicular size from the middle of April until October was associated with a reduction in both the absolute and relative sizes of the haploid and tetraploid cell populations and a concomitant increase in the relative numbers of diploid cells. Measurements of the activity of the soluble Mn2+ -dependent adenylate cyclase revealed seasonal variations that closely paralleled those of the haploid cell population, indicating that, as in other species, the enzyme may be associated with maturing germ cells.

Adenylyl Cyclases↗