A-ring reduction enhances the antigonadotropic potency of norethisterone
| Autor: | Felipe Vilchis, Martha Menjívar, Gustavo A. García, Gregorio Pérez-Palacios, J. Garza-Flores |
|---|---|
| Rok vydání: | 1986 |
| Předmět: |
Male
medicine.medical_specialty Norethisterone medicine.drug_class Endocrinology Diabetes and Metabolism Metabolite Alpha (ethology) Biology chemistry.chemical_compound Endocrinology Isomerism Internal medicine medicine Animals Potency Receptor Beta (finance) Dose-Response Relationship Drug Rats Inbred Strains General Medicine Luteinizing Hormone Norethynodrel Rats Tamoxifen Receptors Estrogen chemistry Receptors Androgen Follicle Stimulating Hormone Norethindrone Gonadotropin Receptors Progesterone Orchiectomy Progestin medicine.drug |
| Zdroj: | Acta Endocrinologica. 112:278-283 |
| ISSN: | 1479-683X 0804-4643 |
| DOI: | 10.1530/acta.0.1120278 |
| Popis: | To assess whether structural modifications on the A-ring of norethisterone (NET) could modify its antigonadotropic potency, comparative studies using NET, 5 alpha-dihydro NET (5 alpha-NET) and its 3 beta,5 alpha and 3 alpha,5 alpha tetrahydro derivatives in castrated adult rats were undertaken. The antigonadotropic effect of these compounds was evaluated by measuring the serum and pituitary immunoreactive concentrations of LH and FSH following their chronic sc administration to animals depleted of progesterone receptors. The results demonstrated that 3 beta,5 alpha-NET and 5 alpha-dihydro-NET exhibited a significantly greater gonadotropic inhibiting activity as compared with that of their parent compound. The simultaneous administration of tamoxifen with 3 beta,5 alpha-NET resulted in a significant diminution of its antigonadotropic potency, particularly for LH. These data indicate that the potent antigonadotropic effect of 3 beta,5 alpha-NET metabolite was mediated via oestrogen receptors. The LH inhibitory activity of 5 alpha-dihydro-NET was not suppressed by the non-steroidal antioestrogen administration, thus suggesting that 5 alpha-NET might exert its effect via androgen receptors. The overall data were interpreted as demonstrating that metabolic conversion products of NET exhibit potent antigonadotropic effect. The data are consistent with an A-ring enhancement of the antigonadotropic potency of this synthetic progestin and open an alternate approach to the development of fertility regulating agents. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|