Sexual Differentiation of the External Genitalia and the Timing of Puberty in the Presence of an Antiandrogen in Sheep
| Autor: | Douglas L. Foster, Leslie M. Jackson, Kathleen M. Timmer |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Sex Differentiation Time Factors medicine.drug_class Disorders of Sex Development Gonadotropin-releasing hormone Biology urologic and male genital diseases Antiandrogen Models Biological Article Flutamide Andrology chemistry.chemical_compound Endocrinology Pregnancy Internal medicine medicine Animals Testosterone Genitalia Sexual Maturation Sheep Estradiol Androgen Antagonists Dihydrotestosterone Luteinizing Hormone Androgen Animals Newborn chemistry Estrogen Prenatal Exposure Delayed Effects Female Luteinizing hormone hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Endocrinology. 149:4200-4208 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2007-1382 |
| Popis: | Testicular steroids during midgestation sexually differentiate the steroid feedback mechanisms controlling GnRH secretion in sheep. To date, the actions of the estrogenic metabolites in programming neuroendocrine function have been difficult to study because exogenous estrogens disrupt maternal uterine function. We developed an approach to study the prenatal actions of estrogens by coadministering testosterone (T) and the androgen receptor antagonist flutamide, and tested the hypothesis that prenatal androgens program estradiol inhibitory feedback control of GnRH secretion to defeminize (advance) the timing of the pubertal increase in LH. Pregnant sheep were either untreated or treated with T, dihydrotestosterone (DHT) (a nonaromatizable androgen), or T plus flutamide from d 30–90 of gestation. To study the postnatal response to steroid negative feedback, lambs were gonadectomized and estradiol-replaced, and concentrations of LH were monitored in twice-weekly blood samples. Although T and DHT produced penile and scrotal development in females, the external genitalia of T plus flutamide offspring remained phenotypically female, regardless of genetic sex. Untreated females and females and males treated with T plus flutamide exhibited a pubertal increase in circulating LH at 26.4 ± 0.5, 26.0 ± 0.7, and 22.4 ± 1.6 wk of age, respectively. In females exposed to prenatal androgens, the LH increase was advanced (T: 12.0 ± 2.6 wk; DHT: 15.0 ± 2.6 wk). These results demonstrate the usefulness of combining T and antiandrogen treatments as an approach to increasing prenatal exposure to estradiol. Importantly, the findings support our hypothesis that prenatal androgens program sensitivity to the negative feedback actions of estradiol and the timing of neuroendocrine puberty. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|