scholarly journals Tissue-selective effects of continuous release of 2-hydroxyestrone and 16alpha-hydroxyestrone on bone, uterus and mammary gland in ovariectomized growing rats

2001 ◽  
Vol 170 (1) ◽  
pp. 165-174 ◽  
Author(s):  
S Lotinun ◽  
KC Westerlind ◽  
RT Turner ◽  
RT Turner
Keyword(s):  
Body Weight ◽  
Mammary Gland ◽  
Weight Gain ◽  
Cancellous Bone ◽  
Bone Growth ◽  
Body Weight Gain ◽  
Biological Activities ◽  
Growing Rats ◽  
Cell Height ◽  
Wet Weight

2-Hydroxyestrone (2-OHE(1)) and 16alpha-hydroxyestrone (16alpha-OHE(1)) have been reported to be risk factors for negative bone balance and breast cancer, respectively. The roles of these two metabolites of estrone as estrogen agonists or antagonists with respect to estrogen target tissues, or both, are poorly defined. The purpose of this study was to characterize metabolite and tissue-specific differences between the actions of hydroxylated estrones on selected reproductive and non-reproductive estrogen target tissues in growing rats. First, the effects of ovariectomy were determined. Ovariectomy had the expected effects, including increases in all dynamic bone measurements at the proximal tibial epiphysis, without induction of bone loss. Second, ovariectomized growing rats were continuously treated for 3 weeks with 2-OHE(1), 16alpha-OHE(1), 17beta-estradiol (E(2)), a combination of E(2) and 2-OHE(1) (E(2)+2-OHE(1)), or a combination of E(2) and 16alpha-OHE(1) (E(2)+16alpha-OHE(1)), using controlled release subcutaneous implanted pellets containing 5 mg 2-OHE(1), 5 mg 16alpha-OHE(1), 0.05 mg E(2) or placebo. E(2) reduced body weight gain and radial and longitudinal bone growth as well as indices of cancellous bone turnover, and increased serum cholesterol, uterine wet weight and epithelial cell height, and proliferative cell nuclear antigen labeling in mammary gland. The hydroxylated estrones did not alter uterine wet weight and 16alpha-OHE(1) antagonized the E(2)-stimulated increase in epithelial cell height. 2-OHE(1) had no effect on cortical bone, whereas 16alpha-OHE(1) was an estrogen agonist with respect to all cortical bone measurements. 16alpha-OHE(1) also behaved as an estrogen agonist with respect to serum cholesterol and cancellous bone measurements. 2-OHE(1) had no effect on most E(2)-regulated indices of cancellous bone growth and turnover, but was a weak estrogen agonist with respect to mineral apposition rate and bone formation rate. Neither estrogen metabolite influenced body weight gain. Third, weanling rats were treated for 1 week with vehicle, E(2) (200 microg/kg per day) or 16alpha-OHE(1) (30, 100, 300, 1000 and 3000 microg/kg per day) to confirm uterotropic effects of daily subcutaneous (s.c.) administration of 16alpha-OHE(1). 16alpha-OHE(1) increased uterine weight in a dose-response manner to values that did not differ from rats treated with E(2). We conclude that the estrogen metabolites 2-OHE(1) and 16alpha-OHE(1) have target tissue-specific biological activities which differ from one another as well as from E(2). These findings add further support to the concept that there are several classes of estrogens with distinct biological activities. Furthermore, differences in the route of administration could influence the tissue specificity of estrogen metabolites.

scholarly journals Dose-Response Effects of 2-Methoxyestradiol on Estrogen Target Tissues in the Ovariectomized Rat

Endocrinology ◽  
2003 ◽  
Vol 144 (3) ◽  
pp. 785-792 ◽  
Author(s):  
J. D. Sibonga ◽  
S. Lotinun ◽  
G. L. Evans ◽  
V. S. Pribluda ◽  
S. J. Green ◽  
...  
Keyword(s):  
Body Weight ◽  
Bone Loss ◽  
Cancellous Bone ◽  
Dose Response ◽  
Bone Growth ◽  
Body Weight Gain ◽  
Hormone Replacement ◽  
Adult Rats ◽  
Cell Height ◽  
Ovx Rats

In three experiments, we evaluated the pharmacological effects of 2-methoxyestradiol (2ME2) on several estrogen target tissues. Experiment 1: we gavaged recently ovariectomized (OVX) 9.5-wk-old rats with 2ME2 at doses of 0, 0.1, 1, 4, 20, and 75 mg/kg in a 21-d dose-response study. 2ME2 reduced body weight and serum cholesterol, increased uterine weight and epithelial cell height, and inhibited longitudinal and radial bone growth compared with values in the untreated OVX rat. All doses of 2ME2 maintained cancellous bone mass at the baseline level, the lowest effective dose being 20-fold less than a uterotrophic dose. Experiment 2: in an 8-wk experiment in adult OVX rats, a nonuterotrophic dose of 2ME2 (4 mg/kg·d) suppressed body weight gain, inhibited bone formation in cancellous bone and partially prevented bone loss in the tibial metaphysis. Experiment 3: in weanling rats, ICI 182,780 did not antagonize the effect of 2ME2. We conclude that 2ME2 antagonizes the skeletal changes that follow OVX at doses that have minimal or no effects in the uterus in both young and adult rats; 2ME2 does not appear to act via estrogen receptors and is active on bone at doses well below those required for tumor suppression in mice. 2ME2, through a novel pathway, may be a useful alternative to conventional hormone replacement therapy for prevention of postmenopausal bone loss.

Effects of Body Weight Gain Reduction Resulting From Chemopreventive Agent Treatment on Mammary Gland Morphology

2002 ◽  
Vol 43 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Cristina Rodríguez-Burford< ◽  
Vernon E. Steele ◽  
Amy S. Anderson ◽  
Cecil R. Stockard ◽  
Heidi L. Weiss ◽  
...  
Keyword(s):  
Body Weight ◽  
Mammary Gland ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Chemopreventive Agent ◽  
Gain Reduction ◽  
Mammary Gland Morphology ◽  
Agent Treatment

ADMINISTRATION OF ANTERIOR PITUITARY GROWTH HORMONE TO RATS DURING COLD EXPOSURE

1963 ◽  
Vol 41 (1) ◽  
pp. 1449-1453
Author(s):  
John R. Beaton ◽  
T. Orme ◽  
J. Laufer ◽  
A. Turner
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Weight Gain ◽  
Cold Exposure ◽  
Anterior Pituitary ◽  
Body Weight Gain ◽  
Nitrogen Retention ◽  
Growing Rats ◽  
Pituitary Growth Hormone ◽  
Environmental Temperatures

Male, growing rats were injected daily with anterior pituitary growth hormone (3 mg/100 g body weight) and fed ad libitum for 7 days at environmental temperatures of 22 °C and 2–3 °C. Body weight gain, nitrogen retention, and four liver enzyme activities were measured. As observed previously, cold exposure retarded body weight gain and decreased nitrogen retention despite an increased food intake. These effects of cold were not eliminated by administration of growth hormone. The increased activities of liver arginase, alanine-glutamic transminase, and phosphate-activated glutaminase consequent upon cold exposure were not significantly affected by growth hormone although, at 22 °C, growth hormone decreased the activities of liver arginase and alanine-glutamic transaminase. Cold exposure eliminated the lowering effect of growth hormone on liver glutamic acid dehydrogenase activity observed at 22 °C. It is concluded that, under these conditions, growth hormone does not overcome the protein catabolic effects of cold exposure but rather, cold exposure eliminates the protein anabolic effects of the hormone.

ADMINISTRATION OF ANTERIOR PITUITARY GROWTH HORMONE TO RATS DURING COLD EXPOSURE

1963 ◽  
Vol 41 (6) ◽  
pp. 1449-1453 ◽  
Author(s):  
John R. Beaton ◽  
T. Orme ◽  
J. Laufer ◽  
A. Turner
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Weight Gain ◽  
Cold Exposure ◽  
Anterior Pituitary ◽  
Body Weight Gain ◽  
Nitrogen Retention ◽  
Growing Rats ◽  
Pituitary Growth Hormone ◽  
Environmental Temperatures

Male, growing rats were injected daily with anterior pituitary growth hormone (3 mg/100 g body weight) and fed ad libitum for 7 days at environmental temperatures of 22 °C and 2–3 °C. Body weight gain, nitrogen retention, and four liver enzyme activities were measured. As observed previously, cold exposure retarded body weight gain and decreased nitrogen retention despite an increased food intake. These effects of cold were not eliminated by administration of growth hormone. The increased activities of liver arginase, alanine-glutamic transminase, and phosphate-activated glutaminase consequent upon cold exposure were not significantly affected by growth hormone although, at 22 °C, growth hormone decreased the activities of liver arginase and alanine-glutamic transaminase. Cold exposure eliminated the lowering effect of growth hormone on liver glutamic acid dehydrogenase activity observed at 22 °C. It is concluded that, under these conditions, growth hormone does not overcome the protein catabolic effects of cold exposure but rather, cold exposure eliminates the protein anabolic effects of the hormone.

Reduced serum concentrations of insulin-like growth factor-I (IGF-I) in protein-restricted growing rats are accompanied by reduced IGF-I mRNA levels in liver and skeletal muscle

1991 ◽  
Vol 130 (2) ◽  
pp. 305-312 ◽  
Author(s):  
M. J. VandeHaar ◽  
B. M. Moats-Staats ◽  
M. L. Davenport ◽  
J. L. Walker ◽  
J.-M. Ketelslegers ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Protein Restriction ◽  
Mrna Abundance ◽  
Factor I ◽  
Growing Rats ◽  
Low Protein ◽  
Igf I

ABSTRACT The serum concentration of insulin-like growth factor-I (IGF-I) is reduced in growing rats fed a low-protein diet, and this decrease is age-dependent, being more pronounced in younger animals. To determine whether this decrease in serum IGF-I is related to a decrease in IGF-I mRNA, growing female rats were given free access to either a 15% protein-sufficient or a 5% protein-deficient diet for 1 week. Protein restriction in 4-week-old rats decreased body weight gain by 44% (P < 0·001) compared with 4-week controls), serum IGF-I concentration by 67% (P < 0·001) and liver IGF-I mRNA abundance by 51% (P < 0·001). During week 6, protein restriction for 1 week resulted in a 20% increase in food intake with no change in weight gain, a 38% reduction in serum IGF-I (P < 0·001 compared with 6-week controls) and a 39% decrease in liver IGF-I mRNA (P < 0·001). The serum IGF-I concentration was highly correlated (r = 0·80; P < 0·001) with the hepatic IGF-I mRNA concentration. Skeletal muscle IGF-I mRNA abundance was also decreased significantly by protein restriction (37% at week 4, P<0·001, and 24% at week 6, P < 0·01) and was closely correlated (r = 0·71; P < 0·001) with body weight gain. Liver GH-binding protein and GH receptor mRNA abundance were reduced by 1 week of protein deprivation at week 6 but not at week 4. We conclude that the reduced serum IGF-I of young rats fed a low-protein diet is due, in part, to reduced liver IGF-I mRNA, and that these changes are not dependent on GH binding. Decreased skeletal muscle IGF-I mRNA during protein restriction is consistent with an autocrine/paracrine action of IGF-I in muscle. Journal of Endocrinology (1991) 130, 305–312

scholarly journals Effects of crowding and heat stress on intestinal flora, body weight gain, and feed efficiency of growing rats and chicks.

1983 ◽  
Vol 45 (3) ◽  
pp. 331-338 ◽  
Author(s):  
Kunio SUZUKI ◽  
Ryo HARASAWA ◽  
Yutaka YOSHITAKE ◽  
Tomotari MITSUOKA
Keyword(s):  
Body Weight ◽  
Heat Stress ◽  
Weight Gain ◽  
Feed Efficiency ◽  
Body Weight Gain ◽  
Intestinal Flora ◽  
Growing Rats

Effects of dietary phytase on body weight gain, body composition and bone strength in growing rats fed a low-zinc diet

2006 ◽  
Vol 17 (3) ◽  
pp. 190-196 ◽  
Author(s):  
James P. McClung ◽  
Chad H. Stahl ◽  
Louis J. Marchitelli ◽  
Nelson Morales-Martinez ◽  
Katherine M. Mackin ◽  
...  
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Weight Gain ◽  
Bone Strength ◽  
Body Weight Gain ◽  
Growing Rats
Sign in / Sign up

Export Citation Format

Share Document