Induction of leyding cell tumors by lacidipine via up-regulation of the LHRH receptor on leyding cells in rats
| Autor: | Yoshihiro Futamura, Yoshimasa Hamada |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
Dihydropyridines endocrine system medicine.medical_specialty Receptor expression Administration Oral Biology Toxicology Rats Sprague-Dawley Mice Nicardipine Species Specificity Internal medicine Proto-Oncogenes medicine Animals Testosterone Receptor Cells Cultured Protein kinase C Leydig cell Leydig Cells Luteinizing Hormone Calcium Channel Blockers Macaca mulatta Rats Up-Regulation Endocrinology medicine.anatomical_structure Bromodeoxyuridine Lacidipine Luteinizing hormone Protein Kinases Receptors LHRH hormones hormone substitutes and hormone antagonists Leydig Cell Tumor Hormone medicine.drug |
| Zdroj: | The Journal of Toxicological Sciences. 23:35-52 |
| ISSN: | 1880-3989 0388-1350 |
| DOI: | 10.2131/jts.23.35 |
| Popis: | Long-term (78 weeks) administration of lacidipine, a dihydropyridine calcium antagonist, increased the incidence of Leydig cell tumors (LCTs) in Sprague-Dawley rats. Lacidipine also increased and decreased the plasma luteinizing hormone (LH) and testosterone levels, respectively. Leydig cells from lacidipine-treated rats showed increases in luteinizing hormone-releasing hormone (LHRH) receptor expression, protein kinase C (PKC) activity, expression of proto-oncogenes, and 5-bromodeoxyridine uptake; whereas their calcium level, LH receptors, and testosterone content decreased. These data suggest that LHRH receptors play an important role in the development of rat LCTs induced by lacidipine, which activates a cascade of cell cycle-regulatory genes via PKC. When isolated Leydig cells were cultured with lacidipine or nicardipine, these changes in rat Leydig cells were not demonstrable in mice and monkeys, species having many fewer testicular LHRH receptors than rats. Thus, lacidipine may pharmacologically induce LCTs in rats but not in mice, with the difference depending on the presence or absence of testicular LHRH receptors. The induction of LCTs by lacidipine in rats is unlikely to occur in humans, since their Leydig cells lack LHRH receptors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|