Tamoxifen fails to block estradiol accumulation, yet is weakly accumulated by the juvenile zebra finch anterior hypothalamus: an autoradiographic study.

In experiment 1, we used autoradiographic procedures to examine whether tamoxifen could displace 3H-estradiol labeling in the anterior hypothalamus and the caudal nucleus of the ventral hyperstriatum (HVc) of ovariectomized 20-day-old female zebra finches. There was no significant reduction in labeling of cells by 3H-estradiol in birds preinjected with unlabeled tamoxifen. In experiment 2, we found that injections of 3H-tamoxifen caused-weak labeling of cells in the anterior hypothalamus of 20-day-old male and female zebra finches. These results are compatible with the idea that tamoxifen does not block the action of estradiol in the brain of zebra finches, and suggest that the effects of early tamoxifen treatment on the morphology of the song system may reflect central actions of tamoxifen.     

Sexual differentiation of the zebra finch song system: Positive evidence,negative evidence,null hypotheses,and a paradigm shift

Permanent sex differences in the brain are found in many vertebrates, and are thought to be induced by sex differences in secretion of gonadal steroid hormones during critical periods of early development. This theory has received support primarily from many experiments conducted on mammals, but also from studies on other vertebrate classes, including birds. The only avian neural dimorphism that has allowed extensive tests of this hypothesis is the neural circuit for song in passerine birds, which is much larger in males than in females. Experiments in zebra finches have yielded contradictory results. Although it is relatively easy to induce masculine patterns of development in genetic females with estrogen, it has not been possible to induce feminine patterns of development in males with any treatments, including antiestrogens and inhibitors of estrogen synthesis. Moreover, genetic females that develop with large amounts of functional testicular tissue but with virtually no ovarian tissue nevertheless have a feminine song circuit. The latter studies fail to support the idea of steroid induction of sexual differentiation. An alternative to the steroidal control hypothesis is that nonhormonal gene products expressed in the brain early in development trigger sexually dimorphic patterns of development. Although current evidence in several neural and nonneural systems indicates that sexual differentiation of some somatic phenotypes cannot be explained by the actions of gonadal steroids, the idea of direct genetic (nonhormonal) induction of sexual differentiation has yet to be proved. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 572–584, 1997     

An autoradiographic study of cellular proliferaton,DNA synthesis and cell cycle variability in the rat liver caused by phenobarbital-induced oxidative stress: The protective role of melatonin

The protective effect of melatonin against phenobarbital-induced oxidative stress in the rat liver was measured based on lipid peroxidation levels (malondialedyde and 4-hydroxyalkenals). Cellular proliferation, DNA synthesis and cell cycle duration were quantitated by the incorporation of ³H-thymidine, detected by autoradiography, into newly synthesized DNA. Two experiments were carried out in this study, each on four equal-sized groups of male rats (control, melatonin [10 mg/kg], phenobabital [20 mg/kg] and phenobarbital plus melatonin). Experiment I was designed to study the proliferative activity and rate of DNA synthesis, and measure the levels of lipid peroxidation, while experiment II was for cell cycle time determination. Relative to the controls, the phenobarbital-treated rats showed a significant increase (P < 0.01) in the lipid peroxidation levels (30.7%), labelling index (69.4%) and rate of DNA synthesis (37.8%), and a decrease in the cell cycle time. Administering melatonin to the phenobarbital-treated rats significantly reduced (P < 0.01) the lipid peroxidation levels (23.5%), labelling index (38.2%) and rate of DNA synthesis (29.0%), and increased the cell cycle time. These results seem to indicate that the stimulatory effect of phenobarbital on the oxidized lipids, proliferative activity, kinetics of DNA synthesis and cell cycle time alteration in the liver may be one of the mechanisms by which the non-genotoxic mitogen induces its carcinogenic action. Furthermore, melatonin displayed powerful protection against the toxic effect of phenobarbital.