Testosterone treatment increases the metabolic capacity of adult avian song control nuclei.

In songbirds, the size of brain nuclei that control song learning and production change seasonally. These changes are mainly controlled by seasonal changes in plasma testosterone (T) concentration. One hypothesis to explain why it may be adaptive for these areas to regress in the fall is that this would decrease the metabolic demand of maintaining a large song system when singing is reduced or absent. We used a marker for cellular metabolism to examine birds with regressed song nuclei and compared them to birds whose song nuclei were induced to grow by administration of exogenous T. Photorefractory male Gambel's white-crowned sparrows were captured during their autumnal migration and kept in outdoor aviaries on a natural photoperiod. We implanted birds with Silastic capsules containing T or with empty implants. Three weeks later the birds were sacrificed. We assayed the brains for cytochrome oxidase (CO) activity and measured the volume of four song nuclei: HVc, RA, 1MAN, and area X. All four nuclei increased in volume in response to T treatment. T treatment increased the metabolic capacity of area X, HVc, and RA relative to surrounding tissue but had no effect on the metabolic capacity of 1MAN. These results support the hypothesis that song nuclei are more metabolically active under the influence of T than they are when plasma T levels are low.

Volumetric analysis of sexually dimorphic limbic nuclei in normal and sex-reversed whiptail lizards.

Sex differences in the size of key limbic nuclei have been found in many species. In some of these species, steroid hormones have been implicated in both the development and the maintenance of the sex difference. However, the possible role of sex-specific genes has not been examined, in part due to lack of an appropriate model system. In this study we measured the size of the ventromedial hypothalamus and preoptic area-anterior hypothalamus in normal female whiptail lizards and in genetic female whiptails that had been sex-reversed by treatment early in development with the aromatase inhibitor fadrozole. We found no difference in the size of these two nuclei between females and the sex-reversed animals. These results suggest that either the sex-reversing treatment itself interfered with the masculinization process, or that a male genome is required to produce a male-like limbic phenotype.

Effect of long-term castration and long-term androgen treatment on sexually dimorphic estrogen-inducible progesterone receptor mRNA levels in the ventromedial hypothalamus of whiptail lizards.

In whiptail lizards, as in laboratory rodents, females will respond to exogenous estrogen by increasing progesterone receptor (PR) or PR mRNA in the ventromedial hypothalamus (VMH) while males show an attenuated response to the same treatment. In rodents, neonatal hormone manipulations affect the adult expression of this trait; however, few investigators have examined the effects of hormone treatment in adulthood. Therefore the current study was carried out to determine whether observed sex differences in the estrogen response in adulthood may be modified by steroid hormone manipulation. We castrated male whiptail lizards for 1 week (short term) or 6 weeks (long term). We also gonadectomized female whiptails and implanted them with either a Silastic capsule containing testosterone or an empty capsule. At the end of that time all implants were removed and the animals were injected with either estradiol benzoate (EB) or steroid suspension vehicle and their brains were assayed for PR mRNA expression using in situ hybridization. The results demonstrate that in male whiptail lizards, long-term castration increases sensitivity to estradiol as measured by induction of PR mRNA in the VMH; EB-injected long-term castrated males were not different from EB-injected females. However, long-term androgenization did not attenuate the estrogen response in females. This suggests that attenuation of the estrogen response in males requires activation by testicular secretions, but that females cannot be made to show a male phenotype via testosterone administration.

Making males from females: the effects of aromatase inhibitors on a parthenogenetic species of whiptail lizard.

The parthenogenetic whiptail lizard Cnemidophorus uniparens provides a good model for the study of sex determination and sexual differentiation because genetic variation is minimal and all unmanipulated embryos will develop as females. Thus any deviation from the established course of development can be identified as a treatment effect. Previous work has shown that early prenatal treatment with CGS16949A, a nonsteroidal aromatase inhibitor, causes hatchlings to develop as males. The present study explores more fully the effects of dosage and timing of application of CGS16949A and examines the sex-reversing potential of CGS20267, a new and reputedly more potent aromatase inhibitor. Eggs were treated with a range of dosages of the aromatase inhibitors. Hatchlings that received 1 microgram or more of either inhibitor were all male, while those that received 0.1 microgram or less were all female. No difference in potency between the two compounds was detected. Animals treated with 100 micrograms of CGS16949A on Day 20 of incubation or later were all female, while those treated on Day 5 were all male. Seven sex-reversed male parthenogens have been raised to sexual maturity. The animals appear similar morphologically and behaviorally to males of the sexually reproducing whiptail species. Spermatogenesis and spermiogenesis have been confirmed by histological examination of the testes and by postcopulatory cloacal swabs. Application of aromatase inhibitors has been shown to sex-reverse both avian and reptilian species. In mammals, the male-determining gene of the Y chromosome (SRY) may code for an intrinsic aromatase inhibitor. Studies show the gene's product has a binding domain which recognizes regulatory elements in the promoter of the aromatase gene.(ABSTRACT TRUNCATED AT 250 WORDS)