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Potential for Estrogen Synthesis and Action in Human Normal and Neoplastic Thyroid Tissues¹

Department of Biology (L.D.V., A.R., S.V., P.B., L.C.) and Institute of Pathological Anatomy (A.F.), University of Padova, Padova, Italy

Address all correspondence and requests for reprints to: Prof. Lorenzo Colombo, Dipartimento di Biologia, Università di Padova, via U. Bassi 58/B, 35121 Padova, Italy. E-mail: colombo{at}civ.bio.unipd.it

To investigate the potential of intracrine or paracrine estrogen synthesis and action in the human thyroid gland and thyroid tumors, the presence of the messenger ribonucleic acids (mRNAs) of both cytochrome P450 aromatase (P450arom) and estrogen receptor (ER) was investigated by RT-PCR with primers designed on the respective coding regions and Southern hybridization analysis with specific probes in neoplastic (n = 42), hyperplastic (n = 7), and adjacent histologically normal thyroid tissues (n = 33) obtained from 43 female and 7 male patients. Most thyroid tissues were positive for both mRNAs, but 2 normal and 3 neoplastic tissues were negative for P450arom mRNA only, 3 normal and 1 hyperplastic tissues were negative for ER mRNA only, and 2 normal tissues were double negative. In some patients, P450arom mRNA was absent in either the neoplastic tissue or the normal one. Single and double negative samples were relatively more frequent in men (n = 4) than in women (n = 7). All negative samples were positive for ß-actin mRNA. RT-PCR amplification and Southern blotting of promoter-specific untranslated 5'-termini revealed that the human thyroid gland and tumors mainly use the ovarian-type promoter, promoter II, for CYP19 expression. Transcripts with either exon I.4 or I.1 were present only in some samples and in very low copy number. When 18 neoplastic samples with their surrounding normal tissues were analyzed immunohistochemically, 57% of those that were positive for P450arom mRNA also had a positive immunoresponse for the corresponding protein. In the case of ER, the percentage was 58%. Immunostaining for P450arom was often particularly intense in neoplastic samples. When 3 adenomata and 1 papillary cancer were incubated with [1,2,6,7-³H]testosterone, 17ß-estradiol could be radiochemically identified with a maximal yield of 10.5 fmol/mg·h.

In conclusion, the human thyroid gland appears to have the potential for both estrogen synthesis and intracrine or paracrine estrogen responsiveness, which seem to be greater in women than men and may become enhanced with the process of tumorigenesis.

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