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.
Endocrinology
; 142(10): 4223-35, 2001 Oct.
Article
em En
| MEDLINE
| ID: mdl-11564678
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tamoxifeno
/
Tri-Iodotironina
/
Moduladores Seletivos de Receptor Estrogênico
/
Estrogênios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Endocrinology
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos