Date of Award:

1966

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Nutrition, Dietetics, and Food Sciences

Department name when degree awarded

Nutrition and Biochemistry

Abstract

Since there is a high incidence of coronary heart disease in humans of middle-age and older in the United States, and the mortality of this disease is still increasing, a great deal of research has been done in this field. Although many theories have been formulated concerning the cause of atherosclerosis, it is a very complex disease, and appears to be influenced by many factors. Disturbed lipid metabolism is widely believed to be involved in the development of the vascular lesions found in arteriosclerosis, although the nature and origin of the disturbance is unknown. The mechanism for the elevation of serum cholesterol and triglyceride levels is not known; but sex hormones and dietary constituents are believed to be among the factors involved.

The concept that atherosclerosis is a metabolic disorder involving lipids and lipoproteins has stimulated extensive investigation of the endocrine influences on circulating lipids and on lipid metabolism. The results have consistently indicated that estrogens decrease circulating cholesterol and prevent cholesterol induced coronary atherosclerosis, while androgen administration tends to increase circulating cholesterol. There are relative few studies of the effect of other sex hormones, such as progesterone. There is only limited information on the relationship between the level of progesterone and the concentration of serum cholesterol in healthy adults while living under ordinary living conditions. Further work with more subjects is desirable.

Since the discovery by Marrian and co-workers (1929) of5β – Pregnane – 3∝,20∝ - diol in urine of pregnant women and the perfection of quantitative method for its determination by Venning (1937), this compound has received wide attention because of its close relation to the metabolism of the corpus luteum hormone, progesterone. Pregnandiol is the major end product of progesterone catabolism and its estimation provides a useful index of luteal function. Progesterone has been isolated from three mammalian tissue sources, the corpus luteum, the adrenal, and the placenta. The function of progesterone is to promote the proliferation of uterine mucosa and thus to prepare this tissue to receive the fertilized ovum.

Cholesterol, literally meaning bile solid-alcohol, derives its name from the fact that it was first isolated from human gallstones, of which it is generally the chief component. The amount of cholesterol in animal tissues varies widely. It is particularly abundant in brain and nerve tissue, adrenal glands, and egg yolk.

It had been shown that the administration of deuterium-labeled cholesterol to a pregnant women gave rise to labeled pregnanediol in the urine. Presumably, the administered cholesterol was converted in the placenta to progesterone, from which pregnanediol was then formed (Fruton et al., 1958). Subsequent work demonstrated that adrenal tissue can convert c14-labeled cholesterol to labeled progesterone, as well as to corticosterone and cortisol, and that cholesterol is a more efficient precursor of the hormones than is acetate.

Observations in animals limited to meal eating rather than ad libitum feeding, have shown that serum cholesterol was significantly raised (Cohn et al., 1962). The rats trained to eat their food in a short period each day also showed markedly increased lipid synthesis. The enhanced lipogenesis resulted in an increase in fat ceposition in adipose tissue. These findings have been interpreted to suggest that using frequent small feedings might prove to be beneficial to people who have abnormal lipid metabolism.

This study is part of a larger problem whose purpose was to determine relationships that exist between serum cholesterol and concentrations of estrogens and the degradation products of androgens, adrenal steroid hormones, and progesterone in urine of healthy young adults consuming self-selected diets under home living conditions. Simultaneous studies of these factors in human subjects have been very limited. The objectives of this study was to determine the levels of serum cholesterol and urinary excretion values of pregnanediol, and any relationships between the two biochemical indices that might exist.

The research was based on a group of university students (five women and four men) maintained on self-chosen diets who were eating two meals per day with no lunch or three meals a day. Urine specimens were collected for hormone estimation and finger-tip blood samples for cholesterol determination. Dietary records were also collected for dietary calculation.

Chemical analyses of free and total cholesterol were made by using the method of Galloway et al. (1957). Determination of prenanediol in urine was made by modification of the method of Eberlein and Bongiovanni (1958) on thin-layer chromatography.

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