Estrogen and tamoxifen interplay with T(3) in male rats: pharmacologically distinct classes of estrogen responses affecting growth, bone, and lipid metabolism, and their relation to serum GH and IGF-I.
Estrogen (E) and T(3) regulate gene expression by receptor mechanisms that may enable hormonal interplay affecting growth and metabolism. Prior studies of E and tamoxifen (TM) interplay with T(3) in female rats identified a subset of E responses that required T(3) for expression and exhibited large agonist responses to TM. In contrast, TM acted more like an antagonist in most T(3)-independent E responses. This study used male rats to further explore the role of T(3) in E effects on growth and metabolism, and the relation of such effects to changes in serum GH and IGF-I. Orchidectomized, hypothyroid rats were treated 6 wk with vehicle, E2 benzoate (E2B), or TM with or without T(3). The following parameters were measured: body weight change; tibia length and bone mineral density; heart and kidney weight; food intake and body temperature; serum levels of glucose, cholesterol, triglycerides, GH, and IGF-I; seminal vesicle weight; and anterior pituitary levels of GH, PRL, glandular kallikrein, and total protein. Interplay with T(3) contributed to multiple E effects on growth and metabolism, and some E responses involved both T(3)-dependent and T(3)-independent components. Both E2B and TM increased serum GH, but the increases were poorly coupled to IGF-I. Correlation/regression analysis of individual rat data sets suggested distinct roles for GH and IGF-I in specific E effects. E2B and TM effects on somatic growth exhibited positive correlations with IGF-I and negative correlations with GH; effects on bone mineral density and triglycerides exhibited positive correlations with GH and negative correlations with IGF-I. Three pharmacologically distinct classes of in vivo E responses were identified in this study, and TM displayed a profile of biological activity that may be useful for men undergoing androgen-deprivation therapy.
Fitts
J M
JM
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.
Klein
R M
RM
Powers
C A
CA
D000818:Animals; D001835:Body Weight / Q000502:physiology; D001842:Bone and Bones / Q000502:physiology; D004347:Drug Interactions; D004967:Estrogens / Q000494:pharmacology* / Q000502:physiology; D013006:Growth Hormone / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011988:Receptors, Thyroid Hormone / Q000502:physiology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology*; D014284:Triiodothyronine / Q000502:physiology*
D004967:Estrogens; D011988:Receptors, Thyroid Hormone; D020845:Selective Estrogen Receptor Modulators; D014284:Triiodothyronine; D013629:Tamoxifen; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone