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Origin of an Ovarian Steroid Cell Tumor Causing Isosexual Pseudoprecocious Puberty Demonstrated by the Expression of Adrenal Steroidogenic Enzymes and Adrenocorticotropin Receptor

Laboratório de Hormônios e Genetica Molecular LIM/42, Unidade de Endocrinologia do Desenvolvimento, Disciplina de Endocrinologia, Hospital das Clinicas (C.J.L., A.A.L.J., A.C.L., S.M., M.C.V.F., R.M.M., I.J.P.A., B.B.M.); and Departamento de Patologia (F.M.C.), Faculdade de Medicina, Universidade de Sao Paulo, CEP 01060–970 Sao Paulo, Brazil

Address all correspondence and requests for reprints to: Berenice B. Mendonca, M.D., Disciplina de Endocrinologia, Hospital das Clinicas, Caixa Postal 3671, CEP 01060–970 Sao Paulo, Brazil. E-mail: beremen{at}usp.br

Ovarian steroid cell tumors are rare neoplasms composed of typical steroid hormone-secreting cells. Most ovarian steroid cell tumors, however, cannot be appropriately classified on a morphological basis, because the neoplastic cells closely resemble adrenal cortical cells. Nevertheless, the true adrenal origin of such tumors has been difficult to demonstrate. Here we report a 3-yr-old girl with isosexual pseudoprecocious puberty due to an ovarian steroid tumor whose adrenal cell origin was determined by the presence of messenger ribonucleic acid (mRNA) of adrenal-specific steroidogenic P450 enzymes (P450c11 and P450c21) and ACTH receptor (ACTHR). Her height was +2.3 SD, and she had Tanner stage III breast development, Tanner stage II pubic hair, and a normal clitoris. Bone age was 5 yr. Basal gonadotropin levels were undetectable (<0.6 U/L for LH and <1.0 U/L for FSH) and remained undetectable after stimulation with 100 µg GnRH, iv. Basal serum testosterone and 17-hydroxyprogesterone levels were slightly elevated, whereas basal serum androstenedione, estradiol, and dehydroepiandrosterone sulfate levels were clearly elevated. Pelvic ultrasound disclosed an enlarged uterus and an adnexal multicystic mass in the right ovary, and pathological studies disclosed an ovarian steroid cell tumor. To establish the cellular origin of the tumor we determined the presence of mRNA for P450c11, P450c21, and ACTHR in tumor tissue and normal adrenal and ovarian tissue. Detection of ACTHR, P450c21, and P450c11 mRNAs isoforms was achieved in tumoral and adrenal control tissue, but not in the ovary control tissue. The RT-PCR products of P450c11 from adrenal control tissue were composed by both BglI-sensitive and -resistant complementary DNAs, indicating the presence of both P450c11AS and P450c11ß, whereas RT-PCR product from the tumor was resistant to BglI digestion, indicating only the presence of P450c11ß.

We conclude that the histological origin of so-called adrenal rest tumor could be reliably determined by assessing the expression of specific genes in the tumor as P450c11ß and P450c21. The use of these molecular tools will allow a more precise classification of an important subset of the ovarian steroid cell tumors and can help to identify ectopic adrenal tissue in ovary and testis.

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