Date of Award
4-14-2015
Document Type
Dissertation
Degree Name
Molecular Biosciences, Ph.D.
First Advisor
Amy Pearce
Committee Members
Anne Grippo; Fabricio Medina-Bolivar; Maureen Dolan; Rebecca Parr
Call Number
LD 251 .A566d 2015 H23
Abstract
Smoking is a major preventable cause of death throughout the world and the need for cessation is unanimously supported by clinicians and scientists. Nicotine in cigarettes is believed to cause tobacco dependence and addiction and low doses of nicotine are found in nicotine replacement therapies (NRT) to mitigate withdrawal symptoms and improve cessation efforts. In addition to smoking associated health risks that are common for men and women, women smokers are more likely to suffer from pregnancy or other reproductive health related complications than non-smokers. Studies show that female smokers are more vulnerable to smoking, and find it harder to quit than men. This creates a clear need for finding suitable smoking cessation aids that are safe for women to use. Despite oral nicotine's potential as a NRT, its effects on vital organs and systems are unknown. Overuse of oral nicotine or improper bodily elimination could be harmful. Therefore it is necessary to assess effects of oral nicotine on female reproductive health and nicotine metabolism before endorsing chronic use of this delivery route for smoking cessation in women. Using a rat model, this dissertation work investigated whether chronic oral nicotine intake alters the estrous cycle and serum estrogen levels or exerts adverse effects in the uterine and ovarian tissues. As the oral route impacts nicotine metabolism, and oral nicotine is subject to hepatic first-pass metabolism, rat sera and urine were analyzed to elucidate distribution and elimination patterns of oral nicotine through its major metabolite and an established biomarker cotinine. Cytochrome P450 2B1/2 (CYP2B1/2) is the major nicotine metabolizing enzyme in rats that converts nicotine to cotinine. The impact of chronic oral nicotine on the CYP2B1/2 mediated nicotine to cotinine conversion pathway was examined. CYP19, or aromatase, an enzyme that is expressed in the brain and ovaries, is inhibited by nicotine in the brain. Aromatase is also the enzyme that converts testosterone to estrogen in ovaries. Since literature indicates a shared influence of nicotine and ovarian hormones in females, this project attempted to investigate if oral nicotine hinders estrogen production by altering CYP19 protein levels and/or activity in the ovaries.
Rights Management
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Halder, Swapnali, "Consumption Of Oral Nicotine: Its Effects on the Reproductive System and Nicotine Metabolism of Female Sprague-Dawley Rats" (2015). Student Theses and Dissertations. 714.
https://arch.astate.edu/all-etd/714
