Stimulatory adrenocortical effects of a selective estrogen receptor modulator in ovariectomized female macaques.
Here, we report the effects of estrogen and the selective estrogen receptor modulator (SERM) levormeloxifene on adrenocortical measures in ovariectomized female cynomolgus monkeys (Macaca fascicularis). Animals were randomized into one of five treatment groups, each containing 23 to 26 animals: (1) placebo, (2) 0.016 mg/kg 17β-estradiol (E(2)), (3) 0.5 mg/kg levormeloxifene (L(1)), (4) 1.0 mg/kg levormeloxifene (L(2)), and (5) 5.0 mg/kg levormeloxifene (L(3)). Treatments were administered orally each day for 18 mo. All doses of levormeloxifene resulted in adrenal weights at least 50% greater than placebo (p < .0001 for all). The target dose of levormeloxifene (L(2)) resulted in higher serum concentrations of cortisol (+63%), dehydroepiandrosterone-sulfate (+73%), and androstenedione (+37%) compared with the placebo group (p < .05 for all). In contrast, E(2) resulted in no significant differences in adrenal weight or adrenocortical steroids. Oral E(2) and all SERM doses resulted in similar reductions in serum gonadotropins and at least threefold greater uterine weight versus placebo (p < .0001 for all). Results indicate that the SERM levormeloxifene, in contrast to E(2), may have robust stimulatory effects on adrenocortical hormones in a postmenopausal model. These findings warrant further investigation into long-term SERM effects on adrenocortical function.
Department of Pathology (Section on Comparative Medicine), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
Charles E
CE
Wood
Ronda C
RC
Stavisky
Jette
J
Nowak
Jay R
JR
Kaplan
D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000728:Androgens / Q000097:blood; D000818:Animals; D001835:Body Weight; D005260:Female; D006062:Gonadotropins / Q000097:blood; D006854:Hydrocortisone / Q000097:blood; D008252:Macaca fascicularis; D009929:Organ Size; D010052:Ovariectomy; D010902:Pituitary Gland / Q000187:drug effects; D011759:Pyrrolidines / Q000008:administration & dosage / Q000633:toxicity*; D012044:Regression Analysis; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000633:toxicity*; D018709:Statistics, Nonparametric; D013268:Stimulation, Chemical; D036401:Toxicity Tests, Chronic
D000728:Androgens; D006062:Gonadotropins; D011759:Pyrrolidines; D020845:Selective Estrogen Receptor Modulators; C108255:levormeloxifene; D006854:Hydrocortisone