The Possible Role of Extra-Gonadal Metabolism of Steroids in The Regulation of Plasma Steroid Levels (Cytochrome P-450, Liver)
Thomford, Peter James
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https://hdl.handle.net/2142/70028
Description
Title
The Possible Role of Extra-Gonadal Metabolism of Steroids in The Regulation of Plasma Steroid Levels (Cytochrome P-450, Liver)
Author(s)
Thomford, Peter James
Issue Date
1985
Department of Study
Animal Sciences
Discipline
Animal Sciences
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Animal Physiology
Abstract
The circulating level of steroid hormones is determined by both the rate of production by the steroidogenic tissue and by the rate of elimination from the circulation. The rate of metabolism of steroid hormones to more water soluble compounds can be influenced by a variety of factors including diet and exposure to lipophilic compounds. Phenobarbital, a commonly used sedative, is known to increase the rate of hepatic metabolism and elimination of estrogen, progesterone and testosterone. The level of dietary protein is known to have a similar, albeit less predictable, effect on hepatic steroid metabolism.
The mixed function oxidase system consists of cytochromes P-450, NADPH cytochrome P-450 reductase and phosphatidyl choline. Together these components hydroxylate lipophilic compounds such as steroids by adding one atom of molecular oxygen and one electron in the form of hydrogen from NADPH. The other atom of oxygen and the other electron are incorporated into a molecule of water. The concentration of cytochromes P-450 and the activity of NADPH cytochrome c reductase are commonly monitored as a measure of total mixed function oxidase activity in hepatic microsomes.
The first objective of the following experiments was to determine the influence of dose of phenobarbital and interval to measurement on the level of mixed function oxidase activity in sheep and pigs. The second objective was to determine if phenobarbital and dietary protein could be used to alter reproductive endocrine events such as ovulation rate, circulating steroid levels, and uterine responsiveness to estrogen.
Therefore, Experiments I and II were designed to determine the relationships between dose of phenobarbital and interval to measurement on hepatic MFO activity in barrows, gilts, and ewes. Experiment III was designed to determine if oral administration of phenobarbital influenced the length of sleeping time induced by pentobarbital anesthesia. Experiment IV was designed to determine if oral administration of phenobarbital altered the clearance rate of progesterone in ovariectomized ewes implanted with silastic capsules containing progesterone. Experiment V was conducted to compare the effects of diet and phenobarbital on the ovulation rates of ewes. Experiment VI was designed to test the hypothesis that estrogen, testosterone and phenobarbital affect uterine weight and MFO activity in a similar fashion.
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