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Am J Physiol Endocrinol Metab ; 297(2): E483-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19491298

RESUMO

Somatostatin (SS) released by hypothalamic neurons inhibits GH exocytosis noncompetitively. Therefore, we postulated that attenuation of GH feedback-induced SS outflow would help to unmask covariates of endogenous secretagogue drive. To this end, 42 healthy pre- and postmenopausal women were randomly assigned to receive leuprolide plus estradiol (E(2)) or leuprolide plus placebo. A putatively low-SS milieu was imposed by L-arginine infusion. Deconvolution and regularity analyses were applied to 6-h GH concentration-time profiles. By two-way ANOVA, age negatively (P < 0.001) and E(2) positively (P = 0.001) determined pulsatile GH secretion in the presumptively SS-deficient milieu (P < 0.001). Comparable effects were exerted on the mass of GH secreted per burst per unit distribution volume (age P = 0.001, E(2) P < 0.001, overall P < 0.001). E(2) alone predicted basal (nonpulsatile) GH secretion (P = 0.004). Stepwise forward-selection multivariate regression demonstrated that age (P = 0.0017) and E(2) (P = 0.0002) together explained 46% of intersubject variability in pulsatile GH secretion (P < 0.001) and fully replaced the negative univariate effect of abdominal visceral fat (r(2) = 0.32, P < 0.001). Moreover, age and E(2) (but not AVF) interacted to supervise GH regularity (P = 0.007). We conclude that age and E(2) availability individually and together constitute primary predictors of basal, pulsatile, and patterned GH secretion in an inferentially feedback-silenced context in healthy women. Therefore, both factors must be considered in framing hypotheses of endogenous GH drive.


Assuntos
Metabolismo Basal/fisiologia , Hormônio do Crescimento Humano/metabolismo , Somatostatina/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Metabolismo Basal/efeitos dos fármacos , Preparações de Ação Retardada/farmacologia , Relação Dose-Resposta a Droga , Entropia , Estradiol/farmacologia , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Leuprolida/administração & dosagem , Leuprolida/farmacologia , Pessoa de Meia-Idade , Placebos , Fluxo Pulsátil/efeitos dos fármacos , Fluxo Pulsátil/fisiologia , Somatostatina/metabolismo , Adulto Jovem
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