Effects of CP-336,156, a New, Nonsteroidal Estrogen Agonist/Antagonist, on Bone, Serum Cholesterol, Uterus, and Body Composition in Rat Models Export

@article{citeulike:1321380, abstract = {We have discovered a new, nonsteroidal, potent estrogen agonist/antagonist, CP-336,156. CP-336,156 binds selectively and with high affinity to the human estrogen receptor-{alpha} with a half-inhibition concentration of 1.5 nM, which is similar to that seen with estradiol (4.8 nM). When given orally to immature (3-week-old) female Sprague-Dawley rats for 3 days at doses of 0.1, 1.0, 10, or 100 {micro}g/kg{middle dot}day, unlike 17{alpha}-ethynyl estradiol, CP-336,156 had no effect on uterine wet or dry weight. Similarly, no uterine hypertrophy was observed in aged (17-month-old) female rats treated (po) with CP-336,156 at 10 or 100 {micro}g/kg{middle dot}day for 28 days. We also found that CP-336,156 decreased total serum cholesterol and fat body mass and had no effect on lean body mass in these aged female rats. In 5-month-old ovariectomized (OVX) Sprague-Dawley female rats, CP-336,156 completely prevented OVX-induced increases in body weight gain, total serum cholesterol, and serum osteocalcin at doses between 10 and 1000 {micro}g/kg{middle dot}day after 4 weeks. At these doses, CP-336,156 completely prevented OVX-induced bone loss and inhibited the increased bone turnover associated with estrogen deficiency in lumbar vertebrae, proximal tibiae, and distal femora. Similar to estrogen, CP-336,156 induced apoptosis and p53 expression with a concomitant decrease in the number of tartrate-resistant acid phosphatase-positive multinuclear cells in rat bone marrow cell cultures in vitro, suggesting that the induction of apoptosis may be a mechanism for the estrogenic activities of CP-336,156 in bone. In summary, CP-336,156 is a new, orally active, nonsteroidal, potent estrogen agonist/antagonist that has similar effects in bone as estradiol but without the uterine-stimulating effects associated with estradiol in rats. 10.1210/en.139.4.2068}, author = {Ke, Hua Z. and Paralkar, Vishwas M. and Grasser, William A. and Crawford, Todd D. and Qi, Hong and Simmons, Hollis A. and Pirie, Christine M. and Chidsey-Frink, Kristin L. and Owen, Thomas A. and Smock, Steven L. and Chen, Hong K. and Jee, Webster S. and Cameron, Kimberly O. and Rosati, Robert L. and Brown, Thomas A. and Dasilva-Jardine, Paul and Thompson, David D.}, citeulike-article-id = {1321380}, citeulike-linkout-0 = {http://dx.doi.org/10.1210/en.139.4.2068}, citeulike-linkout-1 = {http://endo.endojournals.org/cgi/content/abstract/139/4/2068}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/9528995}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=9528995}, day = {1}, doi = {10.1210/en.139.4.2068}, journal = {Endocrinology}, keywords = {agonist, antagonist, body, distribution, estrogen, fat, rat}, month = {April}, number = {4}, pages = {2068--2076}, posted-at = {2007-05-23 13:54:50}, priority = {2}, title = {Effects of CP-336,156, a New, Nonsteroidal Estrogen Agonist/Antagonist, on Bone, Serum Cholesterol, Uterus, and Body Composition in Rat Models}, url = {http://dx.doi.org/10.1210/en.139.4.2068}, volume = {139}, year = {1998} }

TY - JOUR ID - citeulike:1321380 L3 - citeulike-article-id:1321380 N2 - We have discovered a new, nonsteroidal, potent estrogen agonist/antagonist, CP-336,156. CP-336,156 binds selectively and with high affinity to the human estrogen receptor-{alpha} with a half-inhibition concentration of 1.5 nM, which is similar to that seen with estradiol (4.8 nM). When given orally to immature (3-week-old) female Sprague-Dawley rats for 3 days at doses of 0.1, 1.0, 10, or 100 {micro}g/kg{middle dot}day, unlike 17{alpha}-ethynyl estradiol, CP-336,156 had no effect on uterine wet or dry weight. Similarly, no uterine hypertrophy was observed in aged (17-month-old) female rats treated (po) with CP-336,156 at 10 or 100 {micro}g/kg{middle dot}day for 28 days. We also found that CP-336,156 decreased total serum cholesterol and fat body mass and had no effect on lean body mass in these aged female rats. In 5-month-old ovariectomized (OVX) Sprague-Dawley female rats, CP-336,156 completely prevented OVX-induced increases in body weight gain, total serum cholesterol, and serum osteocalcin at doses between 10 and 1000 {micro}g/kg{middle dot}day after 4 weeks. At these doses, CP-336,156 completely prevented OVX-induced bone loss and inhibited the increased bone turnover associated with estrogen deficiency in lumbar vertebrae, proximal tibiae, and distal femora. Similar to estrogen, CP-336,156 induced apoptosis and p53 expression with a concomitant decrease in the number of tartrate-resistant acid phosphatase-positive multinuclear cells in rat bone marrow cell cultures in vitro, suggesting that the induction of apoptosis may be a mechanism for the estrogenic activities of CP-336,156 in bone. In summary, CP-336,156 is a new, orally active, nonsteroidal, potent estrogen agonist/antagonist that has similar effects in bone as estradiol but without the uterine-stimulating effects associated with estradiol in rats. 10.1210/en.139.4.2068 IS - 4 JF - Endocrinology EP - 2076 TI - Effects of CP-336,156, a New, Nonsteroidal Estrogen Agonist/Antagonist, on Bone, Serum Cholesterol, Uterus, and Body Composition in Rat Models VL - 139 SP - 2068 KW - agonist KW - antagonist KW - body KW - distribution KW - estrogen KW - fat KW - rat AU - Ke, Hua AU - Paralkar, Vishwas AU - Grasser, William AU - Crawford, Todd AU - Qi, Hong AU - Simmons, Hollis AU - Pirie, Christine AU - Chidsey-Frink, Kristin AU - Owen, Thomas AU - Smock, Steven AU - Chen, Hong AU - Jee, Webster AU - Cameron, Kimberly AU - Rosati, Robert AU - Brown, Thomas AU - Dasilva-Jardine, Paul AU - Thompson, David PY - 1998/04/01/ UR - http://dx.doi.org/10.1210/en.139.4.2068 ER -