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 m ay enable hormonal interplay affecting growth and metabolism. Prior studies of E and tamoxifen (TM) interplay with T-3 in female rats identified a sub set of E responses that required T-3 for expression and exhibited large ago nist 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 with out T-3. The following parameters were measured: body weight change; tibia length and bone mineral density; heart and kidney weight; food intake and b ody temperature; serum levels of glucose, cholesterol, triglycerides, GH, a nd 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 increas ed serum GH, but the increases were poorly coupled to IGF-I. Correlation/re gression 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 ex hibited positive correlations with IGF-I and negative correlations with GH; effects on bone mineral density and triglycerides exhibited positive corre lations with GH and negative correlations with IGF-I. Three pharmacological ly distinct classes of in vivo E responses were identified in this study, a nd TM displayed a profile of biological activity that may be useful for men undergoing androgen-deprivation therapy.