Date

2013

Department or Program

Biological Chemistry

Title of Approved Individual Major

Biological Chemistry

Primary Wellesley Thesis Advisor

Adele J. Wolfson

Abstract

The enzyme thimet oligopeptidease (TOP) catalyzes the hydrolysis of gonadotropin-releasing hormone (GnRH) in vitro, and evidence suggests that TOP is the primary enzyme responsible for GnRH hydrolysis in vivo, as well. If this is true, TOP could play an important role in regulating steroid hormone production via the hypothalamic-pituitary-gonadal (HPG) axis. In addition to its function at the level of the hypothalamus, TOP may also have a direct effect at the target tissue level. In order to determine if TOP has a direct modulating effect androgen and estrogen functions, prostate cancer cells were treated with estradiol, an end product of the HPG axis. If TOP and steroid hormones comprise a feedback loop, treatment with estradiol could regulate TOP levels, localization or activity. After estradiol treatment, TOP staining was imaged confocally in prostate cancer cells. TOP was also detected and quantified in cell lysates by immunoblot. Quantification of TOP staining in prostate cancer cell images suggested that estradiol treatment increased cellular TOP levels and also increased nuclear TOP levels in particular. However, Western analysis showed that overall TOP levels varied very little with estradiol treatment. Although not definitive, these results indicate that TOP responds differently with direct treatment of prostate cancer cells by estradiol as compared to estradiol treatment within the context of the HPG axis.

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