Propranolol Stimulates Histone Phosphorylation by a Putative PK-C in Partially Purified Homogenate of Rat Testicular Interstitial Cells. A Possible Mechanism for Increased Testosterone Secretion by Propranolol
| Autor: | Daniel P. Udrisar, Antunes-Rodrigues J, Wanderley Mi, Maria do Carmo de Carvalho e Martins |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism Clinical Biochemistry Propranolol Biology Tritium Biochemistry Gonadotropin-Releasing Hormone Histones chemistry.chemical_compound Endocrinology 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Internal medicine Testis medicine Animals Testosterone Enzyme Inhibitors Phosphorylation Rats Wistar Protein kinase A Phorbol 12 13-Dibutyrate Protein Kinase C Protein kinase C Kinase Biochemistry (medical) Leydig Cells General Medicine Chromatography Agarose In vitro Rats Histone phosphorylation chemistry Phorbol medicine.drug |
| Zdroj: | Hormone and Metabolic Research. 32:259-264 |
| ISSN: | 1439-4286 0018-5043 |
| DOI: | 10.1055/s-2007-978632 |
| Popis: | The beta-adrenoceptor blocker propranolol stimulated testosterone secretion by rat testicular interstitial cells (Leydig cell-enriched preparation) in vitro at concentrations ranging from 10(-5) M to 10(-4) M. Treatment of these cells with H7 (20 microM), an inhibitor of protein kinase C, reduced the stimulatory effect of L-propranolol on testosterone secretion by about 5-fold. At concentrations ranging from 31.25 microM to 1000 microM, L-propranolol reduced [3H]phorbol 12,13-dibutyrate binding (IC50 = 75 microM) to rat testicular interstitial cells. At similar concentrations, L-propranolol displaced the binding of [3H]phorbol 12,13-dibutyrate to the homogenate of these cells by only 5%. These findings suggest that the effect of L-propranolol on [3H]phorbol 12,13-dibutyrate binding could be indirect, possibly by increasing the concentration of a chemical mediator interacting with the regulatory domain of protein kinase C. At even lower concentrations (10(-9) M to 10(-7) M), propranolol added directly to the reaction mixture with protein kinase C partially purified from rat testicular interstitial cells increases the phosphorylation of histone. This phosphorylation was comparable to that obtained with (25 microg/ml) phosphatidylserine. The D- and L-stereoisomers of propranolol were equally active. A complete reversal of this propranolol effect on histone phosphorylation was achieved with (20 microM) H-7. In the absence of Ca2+, propranolol was not able to phosphorylate the histone. Taken together, these results suggest that protein kinase C could be the putative kinase involved in this reaction and that its activation by propranolol may be due to interaction of the drug with the regulatory domain of the enzyme at a site differing from the site of interaction with phorbol 12,13-dibutyrate. The ability of propranolol to activate the putative protein kinase C could be related to its stimulatory effect on testosterone secretion by Leydig cells. |
| Databáze: | OpenAIRE |
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