Androgen Regulation of Gene Expression Associated with Cell Growth and Neural Plasticity: Studies in Songbird Brain and the S115 Cell Line

Author

Kent L. Nastiuk

Date of Award

1992

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Clayton Laboratory

Abstract

In order to characterize androgens' effects on the brain and behavior I identified the canary cDNA coding for the nuclear receptor for androgen. The sequence is very conserved over functional domains, but shows some divergence from the only other sequences known, those for rodents and man. The AR mRNA can be localized by in situ hybridization in the canary to the testis and the song nuclei HVc, RA, and MAN. The AR mRNA is regulated by androgens in the periphery in a tissue specific manner. Using a sensitive semi-quantitative per assay, regulation of the AR mRNA by androgen treatment and by natural fluctuations of circulating androgens is seen in the song control nucleus HVc. I used the information about receptor location and the timing of androgen effects to examine androgen induced changes in genes likely be involved in neuronal plasticity. I cloned the canary homolog of the c-jun proto-oncogene, and confirmed its identity based on complete conservation of the important functional domains. I prepared RNA from steroid responsive parts of the brain from ovariectomized canaries treated with testosterone using a simple dot hybridization assay. I could detect a small but rapid induction by androgen of c-jun and two other proto-oncogenes (c-myc and n-myc) in RNA from tissue containing HVc and surrounding telencephalon. Because of this lack of a more dramatic effect in the complex tissue of the brain, I also quantified changes in gene expression induced by androgens in a simpler system. Acting in relative isolation, testosterone can dramatically increase the rate of proliferation of the cells, while estradiol is without effect. Testosterone can increase the mRNA levels of several structural genes, including homologs of genes regulated in the canary brain, and represses several transcription factors in addition to its own receptor. Testosterone also interacts synergistically with the Ca⁺⁺ ionophore A23I87 to induce c-myc and histone H1 expression, where neither alone will do so. In addition, androgen pretreatment represses the TPA-induced increase of these same genes.

Comments

A thesis submitted to the faculty of the Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy

Recommended Citation

Nastiuk, Kent L., "Androgen Regulation of Gene Expression Associated with Cell Growth and Neural Plasticity: Studies in Songbird Brain and the S115 Cell Line" (1992). Student Theses and Dissertations. 372.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/372