Semester

Spring

Date of Graduation

2001

Document Type

Dissertation

Degree Type

PhD

College

Davis College of Agriculture, Natural Resources and Design

Department

Biochemistry

Committee Chair

Joginder Nath.

Abstract

1. Regiospecific expression of CYP1A1 and CYP1B1 in human uterus of nonsmokers. The goal of this study was to investigate the expression of these isoforms in different regions of the human uterus. Expression was determined in the endometrium, endocervix and squamous (exocervix) regions from six nonsmoking women by using RT-PCR. The transcripts encoding for CYP1A1 were significantly higher (p < 0.05) in the squamous (exocervix) region compared to other areas. However the expression of CYP1B1 was significantly higher (p < 0.05) in the endometrium. CYP1B1 expression appeared to be extremely low in a woman in the secretory stage of the menstrual phase, relative to the endometrium of the other patients who were all in the proliferative stage at hysterectomy. It appears that variability in the expression of these isoforms may be responsible for the differential susceptibility to cancer in women.;2. Influence of menstrual phase and smoking status on expression of CYP1A1 and CYP1B1 in different regions of the uterus. The goal of this study was to investigate the expression of these isoforms in different regions of the uterus from smokers and nonsmokers. These results indicate that CYP1A1 and CYP1B1 are expressed variably in different regions of the human uterus. The expression of CYP1B1 may be susceptible both to hormonal control and cigarette smoking. The variability in the expression of these isoforms may be responsible for the differential susceptibility to cancer in some women.;3. The effect of menstrual phase on CYP3A expression in human endometrium. The CYP3A family consists of four closely related proteins. Of these, CYP3A3/4 is the most abundant P450 isoform and is responsible for metabolizing estrogen as well as a variety of therapeutic agents, whereas CYP3A7, the fetal liver form, is involved in the biosynthesis of estriol. The goal of this study was to evaluate the expression of these two major CYP3A isoforms in human uterine tissue during the proliferative (PROL) and secretory (SEC) phases of the menstrual cycle. Expression of CYP3A7 in endometrium appeared to be several fold higher (∼10-fold) in the proliferative phase compared to the secretory phase. CYP3A4 expression was comparable between the two phases of the menstrual cycle. The RTPCR results indicated differential expression of CYP3A7 in various phases of the menstrual cycle. These results indicate that CYP3A isoforms may be subject to hormonal regulation during the menstrual cycle in endometrium of premenopausal women. (Abstract shortened by UMI.).

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