Aberrant Hormone Balance in Fetal Autoimmune NZB/W Mice Following Prenatal Exposure to Testosterone Excess or the Androgen Blocker Flutamide1
| Autor: | F S vom Saal, L W Keisler, P K Rudeen, Duane H. Keisler, Sara E. Walker |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Testosterone Excess
medicine.medical_specialty Fetus medicine.drug_class Offspring chemical and pharmacologic phenomena Cell Biology General Medicine Biology urologic and male genital diseases Antiandrogen Androgen Flutamide chemistry.chemical_compound Endocrinology Reproductive Medicine chemistry immune system diseases Internal medicine medicine skin and connective tissue diseases reproductive and urinary physiology Testosterone Hormone |
| Zdroj: | Biology of Reproduction. 53:1190-1197 |
| ISSN: | 1529-7268 0006-3363 |
| DOI: | 10.1095/biolreprod53.5.1190 |
| Popis: | F, hybrid New Zealand Black (NZB) x New Zealand White (NZW) (NZB/W) mice are hormone-sensitive models of the human disease systemic lupus erythematosus. In this study, NZB/W fetuses produced by pregnant NZB mice were compared with F C57BL/6 x DBA/2 (C57/DBA2) hybrid fetuses produced by nonautoimmune C57BL/6 females. Dams of both strains were treated with testosterone or the androgen blocker flutamide to alter the hormonal environment in late gestation. Hormonal changes in male fetuses carried by treated dams were of interest because hormonal manipulation using either testosterone or flutamide has been shown to increase longevity in male NZB/W offspring. Testosterone-implanted NZB dams developed the expected elevations in circulating maternal testosterone, whereas C57BL/ 6 dams treated with eithertestosterone or flutamide had elevated maternal serum testosterone concentrations. The treatment-induced changes in circulating testosterone in NZB dams and C57BL/6 dams were not reflected in serum from 18-day NZB/W or C57/DBA2 fetuses. Male NZB/W offspring from untreated control NZB dams had unexpectedly high levels of serum estradiol and alpha fetoprotein and relatively low extractable testicular testosterone, compared with nonautoimmune male control fetuses. Maternal testosterone treatments produced a significant decrease in serum estradiol in NZB/W male fetuses, and placental testosterone content was also reduced. Our findings suggest that placental androgen control is regulated differently in the autoimmune NZB-NZB/W vs. the nonautoimmune C57BL/ 6-C57/DBA2 maternal-placental-fetal unit. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|