A series of experiments examined the effects of two
progestins,
progesterone and
R 5020, and two nonsteroidal
antiestrogens,
nafoxidine and
MER-25, on
body weight and composition in female rats. Both
progesterone and
R 5020 increased food intake,
body weight, and carcass adiposity in ovariectomized (OVX) rats treated with
estradiol benzoate (EB), but neither
progestin had any effect on these measures in OVX rats not treated with EB.
R 5020 was substantially more effective than
progesterone on all end points.
Nafoxidine and
MER-25 mimicked the actions of
estradiol and decreased adipose tissue
lipoprotein lipase (LPL) activity by 75-80%. For adipose tissue LPL activity, both
nafoxidine and
MER-25 were full
estrogen agonists and without antiestrogenic activity.
Nafoxidine also mimicked the effects of EB by reducing food intake,
body weight, and carcass adiposity in OVX rats. In contrast,
nafoxidine antagonized the induction of cytoplasmic
progestin ([3H]
R 5020) binding sites by EB in parametrial adipose tissue of OVX rats. In
nafoxidine-treated OVX rats, concurrent
progesterone administration had no effect on adipose tissue LPL activity, but
progesterone did increase food intake,
body weight, and carcass fat content. Some physiological mechanisms by which gonadal
steroids may act to influence eating and adiposity are discussed.