Guanine nucleotide mediated desensitazation of adenylate cyclase in cell free preparations from a Leydig cell tumour

Levi, S. N.; Schumacher, M.; Dix, C. J.; Cooke, Brian A.; Thomas, M. G.

doi:10.1111/j.1365-2605.1982.tb00290.x

Cited by 8 publications

(2 citation statements)

References 12 publications

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“…The inhibitory effect of high GTP concentrations was in contrast to the progressively greater effects of increasing concentrations of the non-hydrolysable analogue, p(NH)ppC. This inhibitory effect of GTP has also been observed in the ovary (Ezra & Salomon 1980) and the testis (Dufau et al 1980) and investigated in the Leydig cell tumour (Levi et al 1982).…”

Section: Discussionmentioning

confidence: 83%

Isolation and characterization of plasma membranes containing LH sensitive adenylate cyclase from a Leydig cell tumour

et al. 1982

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An LH sensitive adenylate cyclase from a tumour Leydig cell has been investigated. The plasma membranes, prepared by a 2 phase (dextran-polyethylene glycol) centrifugation method were found to have the following properties: In the presence of LH plus p(NH)ppG (guanosine 5'-beta, gamma-imido triphosphate) or fluoride ions, maximum adenylate cyclase activity was obtained in the plasma membranes with 4 to 6 mM Mg2+ plus 0.33 to 2 mM ATP. LH alone stimulated adenylate cyclase activity 2-fold when compared with basal activity and the time course of cyclic AMP production was linear up to 45 min. With GTP (10(-5)M) and GTP plus LH, adenylate cyclase activity was increased 3 and 6-fold, respectively, for up to 20 min and thereafter declined. In contrast p(NH)ppG (10(-5)M) and p(NH)ppG plus LH increased adenylate cyclase activity 7 and 14-fold which was maintained for at least 45 min. Fluoride ions increased the enzyme activity linearly over 45 min approx 18-fold. When GTP or p(NH)ppG were added alone there was a lag time of activation of approximately 10 min which was abolished by the addition of LH. GTP but not p(NH)ppG at concentrations greater than 10(-4) inhibited basal and LH stimulated adenylate cyclase when compared with 10(-5)M GTP. The tumour Leydig cell adenylate cyclase is thus essentially similar to other hormone sensitive somatic cells. The present study makes it feasible to prepare plasma membranes by a simple method from large quantities of pure Leydig cells.

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Section: Discussionmentioning

confidence: 83%

Isolation and characterization of plasma membranes containing LH sensitive adenylate cyclase from a Leydig cell tumour

et al. 1982

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“…This early lesion may involve a cyclic AMP-independent phosphorylation of either the receptor or the G-protein (Hunzicker-Dunn et al, 1979). There is some evidence that LH-induced desensitization may involve a GTP-dependent phosphorylation (Ezra & Salomon, 1980;Levi et al, 1982). We have previously demonstrated that the functional transfer of Gprotein from human erythrocytes can reverse LHinduced desensitization in rat tumour Leydig cell plasma membranes indicating that the G-protein is the site of the early lesion in rat Leydig tumour cells.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the homologous and heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase

Dix¹,

Habberfield²,

Cooke³

1984

Biochemical Journal

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The homologous and heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase induced by lutropin (LH) was characterized with the aid of forskolin and cholera toxin. Forskolin stimulated cyclic AMP production in a dose-dependent manner, with linear kinetics up to 2h. Forskolin also potentiated the action of LH on cyclic AMP production, but was only additive with cholera toxin. Preincubation of rat Leydig tumour cells with LH (1.0 micrograms/ml) for 1 h produced a desensitization of the subsequent LH (1.0 micrograms/ml)-stimulated cyclic AMP production, whereas the responses to cholera toxin (5.0 micrograms/ml), forskolin (100 microM), LH plus forskolin or cholera toxin plus forskolin were unaltered. In contrast, preincubation with LH for 20h produced a desensitization to all the stimuli tested. When rat Leydig tumour cells were preincubated for 1h with forskolin or dibutyryl cyclic AMP, the only subsequent response that was significantly altered was that to LH plus forskolin after preincubation with forskolin. However, preincubation for 20h with forskolin or dibutyryl cyclic AMP induced a desensitization to all stimuli subsequently tested. LH produced a rapid (0-1h) homologous desensitization, which was followed by a slower (2-8h)-onset heterologous desensitization. Forskolin and dibutyryl cyclic AMP were only able to induce heterologous desensitization. The rate of desensitization induced by either forskolin or dibutyryl cyclic AMP was similar to the rate of heterologous desensitization induced by LH. These results demonstrate that in purified rat Leydig tumour cells LH produces an initial homologous desensitization of adenylate cyclase that involves a cyclic AMP-independent lesion at or proximal to the guanine nucleotide regulatory protein (G-protein). This is followed by heterologous desensitization, which can also be induced by forskolin or dibutyryl cyclic AMP, thus indicating that LH-induced heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase involves a cyclic AMP-dependent lesion that is after the G-protein.

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

Erichsen

Jahnsen

Andersen

et al. 1984

Journal of Steroid Biochemistry

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Guanine nucleotide mediated desensitazation of adenylate cyclase in cell free preparations from a Leydig cell tumour

Cited by 8 publications

References 12 publications

Isolation and characterization of plasma membranes containing LH sensitive adenylate cyclase from a Leydig cell tumour

Isolation and characterization of plasma membranes containing LH sensitive adenylate cyclase from a Leydig cell tumour

Characterization of the homologous and heterologous desensitization of rat Leydig-tumour-cell adenylate cyclase

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

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