Replacement of surgical castration by GnRH-inhibition or Leydig cell ablation in the male rat Hershberger antiandrogen assay
| Autor: | R. Deghenghi, N. Wallis, John Ashby, P.A. Lefevre |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty Insecticides medicine.drug_class Hormone Replacement Therapy Dichlorodiphenyl Dichloroethylene Biology urologic and male genital diseases Toxicology Antiandrogen Flutamide Gonadotropin-Releasing Hormone chemistry.chemical_compound 5-alpha Reductase Inhibitors Hormone Antagonists Internal medicine medicine Animals Orchiectomy Enzyme Inhibitors Testosterone Mesylates Dose-Response Relationship Drug Body Weight Finasteride Leydig Cells Androgen Antagonists Rats Inbred Strains General Medicine Organ Size Androgen Rats Castration Endocrinology chemistry Dihydrotestosterone Oligopeptides hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Regulatory toxicology and pharmacology : RTP. 34(2) |
| ISSN: | 0273-2300 |
| Popis: | An obstacle to the widespread adoption of the Hershberger antiandrogen assay is the surgical castration procedure required to produce androgen deficiency in the test animals. Here we describe two chemical treatments that produce similar effects to surgical castration. The first is use of ethane dimethane sulphonate (EDS), a specific toxin to the testosterone-producing Leydig cells of the mature testes. The second class of compound is the decapeptide inhibitors of the gonadotrophin-releasing hormone (GnRH), compounds such as Antarelix and Antide. Administration of either EDS or the GnRH inhibitors results in loss of weight of the testes, epididymides, and sex-associated tissues. Co-administration of testosterone to these animals leads to reversal of the induced effects. The basic test protocol for both of these assay modifications is described. Flutamide was used as a representative potent antiandrogen, and DDE as an example of a weakly active antiandrogen. The 5alpha-reductase inhibitor finasteride was used to inhibit the transformation of testosterone to dihydrotestosterone. It is shown that the EDS assay is sensitive to the antiandrogen flutamide, but that it fails to detect the weaker antiandrogen DDE. In contrast, the Antarelix assay performs as well as does the classical castration assay, leading to the detection as antiandrogens of flutamide, DDE, and finasteride. It is concluded that the GnRH inhibition Hershberger assay is more convenient to conduct than the original surgical castration assay, and it involves less stress to the test animals. |
| Databáze: | OpenAIRE |
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