Gonadotropin-induced adrenocortical neoplasia in NU/J nude mice

Malgorzata Bielinska, Elena Genova, Irving Boime, Helka Parviainen, Sanne Kiiveri, Juhani Leppäluoto, Nafis Rahman, Markku Heikinheimo, David B. Wilson

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


In response to prepubertal gonadectomy certain inbred mouse strains, including DBA/2J, develop sex steroid-producing adrenocortical neoplasms. This phenomenon has been attributed to a lack of gonadal hormones or a compensatory increase in gonadotropins. To assess the relative importance of these mechanisms, we created a new inbred model of adrenocortical neoplasia utilizing female NU/J nude mice. These mice developed adrenocortical neoplasms in response to either gonadectomy or gonadotropin elevation from xenografts of hCG-secreting CHO cells. In each instance the adrenal tumors resembled the neoplasms found in gonadectomized DBA/2J mice and were composed of spindle-shaped A cells and lipid-laden B cells. Both cell populations were defined by ectopic expression of GATA-4 and an absence of the adrenocortical markers melanocortin-2-receptor and steroid 21-hydroxylase, but only B cells expressed the gonadal steroidogenic markers inhibin-α, LH receptor, P450c17, and P450c19. Expression of sex steroidogenic markers was attenuated in the neoplastic adrenal cortex of hCG-treated versus gonadectomized mice. While neoplastic adrenals were an obvious source of estradiol in gonadectomized mice, ovaries appeared to be the major source of this hormone in hCG-treated mice. Gonadectomy and hCG-treatment elicited comparable increases in serum estradiol, but testosterone levels increased significantly only in hCG-treated mice. We conclude that chronic gonadotropin elevation, caused either by gonadectomy or hCG administration, signals a population of cells in the adrenal subcapsular region of permissive mice to undergo differentiation along a gonadal rather than an adrenal lineage. Thus, NU/J nude mice can be used as a model to study both neoplasia and adrenogonadal lineage specification.

Original languageEnglish
Pages (from-to)3975-3984
Number of pages10
Issue number9
StatePublished - Sep 2005


  • Adrenal tumor
  • Metaplasia
  • Ovariectomy
  • Steroidogenesis
  • Transdifferentiation
  • Xenograft


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