Gonadectomy-induced adrenocortical neoplasia in the domestic ferret (Mustela putorius furo) and laboratory mouse

被引:62
作者
Bielinska, M
Kiiveri, S
Parviainen, H
Mannisto, S
Heikinheimo, M
Wilson, DB
机构
[1] Washington Univ, St Louis Childrens Hosp, Dept Pediat, Sch Med, St Louis, MO 63110 USA
[2] Washington Univ, St Louis Childrens Hosp, Dept Mol Biol & Pharmacol, Sch Med, St Louis, MO 63110 USA
[3] Univ Helsinki, Childrens Hosp, Biomedicum, Program Dev & Reprod Biol, Helsinki, Finland
[4] Univ Tampere, FIN-33101 Tampere, Finland
[5] Univ Tampere, Cent Hosp, FIN-33101 Tampere, Finland
关键词
adrenal tumor; ferrets; luteinizing hormone; mice; orchiectomy; ovariectomy; steroidogenesis;
D O I
10.1354/vp.43-2-97
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Sex steroid-producing adrenocortical adenomas and carcinomas occur frequently in neutered ferrets, but the molecular events underlying tumor development are not well understood. Prepubertal gonadectomy elicits similar tumors in certain inbred or genetically engineered strains of mice, and these mouse models shed light on tumorigenesis in ferrets. In mice and ferrets, the neoplastic adrenocortical cells, which functionally resemble gonadal steroidogenic cells, arise from progenitors in the subcapsular or juxtamedullary region. Tumorigenesis in mice is influenced by the inherent susceptibility of adrenal tissue to gonadectomy-induced hormonal changes. The chronic elevation in circulating luteinizing hormone that follows ovariectomy or orchiectomy is a prerequisite for neoplastic transformation. Gonadectomy alters the plasma or local concentrations of steroid hormones and other factors that affect adrenocortical tumor development, including inhibins, activins, and Mullerian inhibiting substance. GATA-4 Immunoreactivity Is a hallmark of neoplastic transformation, and this transcription factor might serve to integrate intracellular signals evoked by different hormones. Synergistic interactions among GATA-4, steroidogenic factor-1, and other transcription factors enhance expression of inhibin-a and genes critical for ectopic sex steroid production, such as cytochrome P450 17 alpha-hydroxylase/17,20 lyase and aromatase. Cases Of human adrenocortical neoplasia have been linked to precocious expression of hormone receptors and to mutations that alter the activity of G-proteins or downstream effectors. Whether such genetic changes contribute to tissue susceptibility to neoplasia in neutered ferrets and mice awaits further Study.
引用
收藏
页码:97 / 117
页数:21
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