RESUMO
The aim of the present study was to investigate the influence of thyroid hormones on androgen metabolism in Sertoli cells isolated from 3- and 4- week-old rats. Hypothyroidism was induced by the oral administration of 0.025% methimazole (MMI) from birth until the rats were killed at 3 and 4 weeks of age. Half of the MMI-treated animals were injected i.p. with L-triiodothyronine (T3 3 micrograms/100 g body weight) during the last week before death. Sertoli cells from all groups were initially cultured under basal conditions for the first 24 h and subsequently in the presence of testosterone with or without T3 for an additional 24 h. Hypothyroidism was associated with severe impairment of body as well as testicular growth. Indeed, body and testicular weights were similar in 4-week-old hypothyroid animals to those in 3-week-old control rats. Testosterone metabolism in Sertoli cells isolated from 3- and 4-week-old hypothyroid rats was mainly expressed by the lowering of 5 alpha-dihydrotestosterone + androstane 3 alpha, 17 beta-diol and an enhanced formation of 5 alpha-reduced steroids with poor androgenic properties (e.g. 5 alpha-androstane, 3, 17 alpha-dione (androstanedione), 5 alpha-androstane, 3-ol-17-one (androsterone)). Treatment of the same group of animals with T3 in vivo and in vitro did not influence the pattern of 5 alpha-reductase steroids substantially. The most striking finding in the Sertoli cells of 3-week-old hypothyroid rats was the dramatic enhancement of oestradiol formation which persisted to a lesser extent 1 week later.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Androgênios/metabolismo , Hipotireoidismo/metabolismo , Células de Sertoli/metabolismo , Maturidade Sexual/fisiologia , Tri-Iodotironina/farmacologia , Androstano-3,17-diol/metabolismo , Androstenodiona/metabolismo , Androsterona/metabolismo , Animais , Peso Corporal/fisiologia , Células Cultivadas , Di-Hidrotestosterona/metabolismo , Estradiol/metabolismo , Masculino , Metimazol , Tamanho do Órgão/fisiologia , Ratos , Ratos Wistar , Células de Sertoli/efeitos dos fármacos , Testículo/anatomia & histologia , Testosterona/metabolismoAssuntos
Hormônio do Crescimento/metabolismo , Talassemia beta/fisiopatologia , Adolescente , Transfusão de Sangue , Terapia por Quelação , Criança , Terapia Combinada , Desferroxamina/uso terapêutico , Nanismo/etiologia , Nanismo/fisiopatologia , Feminino , Hormônio Liberador de Hormônio do Crescimento , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Puberdade , Brometo de Piridostigmina , Somatostatina/fisiologia , Talassemia beta/complicações , Talassemia beta/terapiaRESUMO
A Calabrian family (Southern Italy) with Sp alpha(I/74) hereditary elliptocytosis (HE) in the heterozygous state was studied. Sp alpha(I/74) HE is associated with asymptomatic elliptocytosis, a defect in spectrin dimer self association and an increase of the alpha(I/74) kD fragment from the alpha chain after partial tryptic digestion of spectrin. To identify the underlying molecular defect, we analysed exons V, W, X, Y, Z of the beta gene and exon 2 of the alpha gene by single-strand conformational polymorphism (SSCP) of the amplification products. Direct DNA sequencing of the mutant exon showed a C-->G substitution at position 6284 of the beta gene. The corresponding substitution at the protein level was Arg-->Pro in the 2064 position of the beta-spectrin chain.