Prenatal Influence of an Androgen Agonist and Antagonist on the Differentiation of the Ovine Sexually Dimorphic Nucleus in Male and Female Lamb Fetuses
| Autor: | Hernán J. Montilla, Mary Meaker, Charles E. Roselli, Melissa Scheldrup, Charles T. Estill, Fred Stormshak, Radhika C. Reddy |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Hypothalamo-Hypophyseal System medicine.medical_specialty medicine.drug_class Biology urologic and male genital diseases Flutamide chemistry.chemical_compound Endocrinology Pregnancy Internal medicine medicine Animals Testosterone Sexually dimorphic nucleus Kisspeptins Sex Characteristics Sheep Sexual differentiation Androgen Antagonists Dihydrotestosterone Luteinizing Hormone Androgen Preoptic Area Androgen receptor chemistry Reproduction-Development Receptors Androgen Hypothalamus Androgens Female medicine.drug |
| Zdroj: | Endocrinology. 155:5000-5010 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2013-2176 |
| Popis: | The ovine sexually dimorphic nucleus (oSDN) is 2 times larger in rams than in ewes. Sexual differentiation of the oSDN is produced by testosterone exposure during the critical period occurring between gestational day (GD)60 and GD90 (term, 147 d). We tested the hypothesis that testosterone acts through the androgen receptor to control development of the male-typical oSDN. In experiment 1, pregnant ewes received injections of vehicle, androgen receptor antagonist flutamide, or nonaromatizable androgen dihydrotestosterone (DHT) propionate during the critical period. Fetuses were delivered at GD135. Both antagonist and agonist treatments significantly reduced mean oSDN volume in males but had no effects in females. Experiment 2, we analyzed the effect of treatments on the fetal hypothalamic-pituitary-gonadal axis to determine whether compensatory changes in hormone secretion occurred that could explain the effect of DHT. Pregnant ewes were injected with vehicle, flutamide, or DHT propionate from GD60 to GD84, and fetuses were delivered on GD85. Flutamide significantly increased LH and testosterone in males, whereas DHT significantly decreased both hormones. In females, LH was unaffected by flutamide but significantly reduced by DHT exposure. DHT significantly decreased pituitary gonadotropin and hypothalamic kisspeptin mRNA expression in males and females. These results suggest that androgen receptor mediates the effect of testosterone on oSDN masculinization, because this process was blocked by the androgen receptor antagonist flutamide in eugonadal males. In contrast, the reduction of oSDN volume observed after DHT exposure appears to be mediated by a negative feedback mechanism exerted on the hypothalamus to reduce LH and testosterone secretion. The reduced androgen exposure most likely accounted for the decreased oSDN volume. We conclude that, during the critical period, the male reproductive axis in long gestation species, such as sheep, is sufficiently developed to react to perturbations in serum androgens and mitigate disruptions in brain masculinization. |
| Databáze: | OpenAIRE |
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