LOCALIZATION OF ESTROGEN-RECEPTORS IN INTERSTITIAL-CELLS OF HAMSTER-KIDNEY AND IN ESTRADIOL-INDUCED RENAL TUMORS AS EVIDENCE OF THE MESENCHYMAL ORIGIN OF THIS NEOPLASM

The mechanism of estrogen-induced and -dependent kidney carcinogenesis in Syrian hamsters and the cell of origin of the tumor are not well u nderstood; they have been investigated in this study by mapping the ce llular locations of estrogen receptor (ER) in estrogen-dependent tumor s, in kidney tissue of hamsters treated with estradiol for 0.5 and 5.5 months, and in kidneys of age-matched controls. To validate the metho ds used, receptors have also been localized in uteri of hamsters and r ats and in female hamster kidneys. ERs have been identified in cryosta t sections by immunocytochemical techniques using an affinity-purified ER antibody, ER-715. Nuclei of tumors were intensely stained for ERs. In estrogen-treated kidneys and in controls, ER protein was identifie d in interstitial cells and capillaries, in arteries, and in renal cor puscles, particularly in podocytes and in the parietal layers surround ing the renal corpuscles. There was no ER protein in tubular epithelia even when tubuli were surrounded by tumor cells. The ER distribution in female hamster kidneys closely matched that in male kidneys. Howeve r, the staining intensity was stronger in female than in male kidneys. In hamster uteri, there was an intense ER-positive reaction in the nu clei of stroma, in stromal vessels, and in the luminal epithelia as de monstrated previously by others in rat uteri. ER mRNA has also been de monstrated by Northern blot analysis in estrogen-treated kidneys which contained tumors but was undetectable in untreated kidneys. The local ization of ERs in estrogen-dependent tumors and in interstitial cell t ypes but not in tubular epithelia supports previous conclusions of an interstitial origin of estrogen-induced hamster kidney tumors.