Abstract

To probe the mechanism of the sex differential in lipoprotein metabolism (and in turn the sex differential in atheroslcerosis and indeed longevity itself in Occidental societies), exogegnous progestin or estrogen will be administered to normolipidemic post-menopausal women. The effects of a non-androgenic progestin (medroxyprogesterone) will be contrasted with those of an androgenic 19-nortestosterone derivative (norgestrel), a primarily premenopausal estrogen (17Beta-estradiol), and a post-menopausal estrogen (estrone). Paired studies of plasma lipids, lipoproteins (VLDL, IDL, LDL, HDL2, HDL3), apolipoproteins (B, A-I, A-II, E) post-heparin plasma hepatic triglyceride lipase (HTGL) and lipoprotein lipase (LPL), will be performed before and during 3 graduated doses of the progestin or estrogen. Subjects will be given a metabolic isocaloric diet of 40% F, 45% CHO, 15% P, P/S 0.8, cholesterol 450 mg/d throughout the study. Radio-iodinated apolipoprotein turnover (VLDL apoB, and apoA-I) will be performed before administration of the progestin or estrogen and during the high dose of the steroid. Multicompartmental mathematical modelling will be performed to analyze the regulation of lipoprotein metabolism in the basal state and its modulation by the progestin and estrogen using the results of the steady state tracer studies to constrain modelling of the non-steady state unlabelled lipid, lipoprotein, apoprotein, and post-heparin plasma triglyceride lipase data.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL038624-01
Application #
3354914
Study Section
(SRC)
Project Start
1986-09-30
Project End
1988-09-28
Budget Start
1986-09-30
Budget End
1987-09-29
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Wake Forest University Health Sciences
Department
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106

  Publications

Colvin Jr, P L; Auerbach, B J; Case, L D et al. (1991) A dose-response relationship between sex hormone-induced change in hepatic triglyceride lipase and high-density lipoprotein cholesterol in postmenopausal women. Metabolism 40:1052-6
Colvin Jr, P L; Auerbach, B J; Koritnik, D R et al. (1990) Differential effects of oral estrone versus 17 beta-estradiol on lipoproteins in postmenopausal women. J Clin Endocrinol Metab 70:1568-73
Auerbach, B J; Parks, J S; Applebaum-Bowden, D (1990) A rapid and sensitive micro-assay for the enzymatic determination of plasma and lipoprotein cholesterol. J Lipid Res 31:738-42
Applebaum-Bowden, D; McLean, P; Steinmetz, A et al. (1989) Lipoprotein, apolipoprotein, and lipolytic enzyme changes following estrogen administration in postmenopausal women. J Lipid Res 30:1895-906