title: Gonadotropin-induced adrenocortical neoplasia in NU/J nude mice.
abstract: 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 using female NU/J nude mice. These mice developed adrenocortical neoplasms in response to either gonadectomy or gonadotropin elevation from xenografts of human chorionic gonadotropin (hCG)-secreting Chinese hamster ovary 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-alpha, LH receptor, P450c17, and P450c19. Expression of sex steroidogenic markers was attenuated in the neoplastic adrenal cortex of hCG-treated vs. gonadectomized mice. Whereas 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 by either 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.
authors.affiliation: Department of Pediatrics, Box 8208, Washington University School of Medicine, St. Louis Children's Hospital, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Bielinska
authors.forename: Elena
authors.initials: E
authors.lastname: Genova
authors.forename: Irving
authors.initials: I
authors.lastname: Boime
authors.forename: Helka
authors.initials: H
authors.lastname: Parviainen
authors.forename: Sanne
authors.initials: S
authors.lastname: Kiiveri
authors.forename: Juhani
authors.initials: J
authors.lastname: Leppäluoto
authors.forename: Nafis
authors.initials: N
authors.lastname: Rahman
authors.forename: Markku
authors.initials: M
authors.lastname: Heikinheimo
authors.forename: David B
authors.initials: DB
authors.lastname: Wilson
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism / Q000473:pathology; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000097:blood / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006062:Gonadotropins / Q000097:blood*; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics / Q000378:metabolism; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D012333:RNA, Messenger; D044103:Receptor, Melanocortin, Type 2; D013255:Steroid 21-Hydroxylase