Reference SummaryBeamer WG, Cancer Res 1988 May 15;48(10):2788-92

Title	Induction of ovarian granulosa cell tumors in SWXJ-9 mice with dehydroepiandrosterone.
Authors	Beamer WG; Shultz KL; Tennent BJ
Journal	Cancer Res
Volume	48
Issue	10
Year	1988
Pages	2788-92
Abstract	Spontaneous ovarian granulosa cell (GC) tumors develop in SWXJ-9 inbred mice at approximately the time of puberty. The effect of dehydroepiandrosterone (DHEA), a steroid secreted by the adrenals and reported to have antitumor actions, was examined in this ovarian tumor model. In contrast with expectations, administration of diet supplemented with 0.4% DHEA or Silastic capsules containing 10 mg DHEA resulted in a significant multifold increase in GC tumor incidence. Similar studies with metabolites of DHEA, i.e., testosterone (TESTO), dihydrotestosterone (DHT), and 17 beta-estradiol (E2), revealed that TESTO was as effective as DHEA in increasing GC tumor incidence. DHT was without effect, and E2 suppressed GC tumor incidence. Serum steroid levels and steroid target tissue responses were assessed to determine if a correlation between a change in level or response to specific steroids and GC tumorigenesis existed. In both tumor-free and GC tumor host mice, dietary or capsular treatment with DHEA, TESTO, or DHT resulted in substantial alteration in one or more of serum steroids, DHEA, androstenedione, TESTO, and DHT, in addition to the administered steroid. No consistent correlation was observed between changes in a single steroid or pattern of steroids and GC tumorigenesis. Although significant increases in serum estrogens could be detected in GC tumor hosts treated with DHEA but not TESTO, estrogens did not induce these tumors. Treatment with E2 increased only serum E2 levels. In tumor-free mice, DHEA and E2 treatments were associated with vaginal cytological evidence of estrogen action, whereas the androgens induced a leukocytic pattern. Eighty-eight % of GC tumor host mice, regardless of steroid treatment, showed a vaginal cytology pattern that included cornified cells. The evidence presented in this report leads us to hypothesize that (a) spontaneous and steroid-induced GC tumorigenesis in these mice have the same mechanism, and (b) subtle increases in DHEA or a closely related metabolite during the peripubertal period may initiate GC tumors in these genetically susceptible mice. The mechanism whereby these steroids initiate GC tumorigenesis remains to be determined.
Links	J:27621 – MGI References 2965969 – National Library of Medicine/PubMed

Models
Strain	Model Name	Treatment Agent(s)	Organ Affected	Frequency	Model Details
SWXJ9/BmJ	Ovary - Granulosa cell tumor		Ovary - Granulosa cell	4.6 - 7.1
SWXJ9/BmJ	Ovary - Granulosa cell tumor	dehydroepiandrosterone (DHEA)	Ovary - Granulosa cell	26 - 43
SWXJ9/BmJ	Ovary - Granulosa cell tumor	testosterone	Ovary - Granulosa cell	30 - 32
SWXJ9/BmJ	Ovary - Granulosa cell tumor	dihydrotestosterone (DHT)	Ovary - Granulosa cell	8.3
SWXJ9/BmJ	Ovary - Granulosa cell tumor	17beta-estradiol (E2)	Ovary - Granulosa cell	0 - 2.1