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Effects of Estradiol Treatment and/or Ovariectomy on Spontaneous Hemorrhagic Lesions in the Pancreatic Islets of Sprague-Dawley Rats

¹ Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13 Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan
² Research Department III, Daiichi Sankyo RD associe Co., Ltd., 3-10-2 Kita-Shinagawa, Shinagawa-ku, Tokyo 140-0001, Japan
³ Shinwa BioCraft Laboratory Inc., 1-44 Edogawa, Edogawa-ku, Tokyo 132-0013, Japan

Correspondence: Masako Imaoka, D.V.M., Group I, Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13, Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan; e-mail:imaoka.masako.hf{at}daiichisankyo.co.jp.

The present study was conducted to investigate the effect of estradiol treatment and/or ovariectomy (OVX) on non-neoplastic lesions in the pancreatic islets of Sprague-Dawley rats. Males were divided into non-treatment (naïve) and β-estradiol 3-benzoate (EB) treatment groups and females into naïve, sham-operation, OVX, and OVX plus EB treatment groups. EB was subcutaneously administered once a week from seven to twenty-six weeks of age. The animals were euthanized at twelve, eighteen, and twenty-six weeks of age, and the serum estradiol concentrations were measured in conjunction with the pancreatic islet histopathology. The histological stages of pancreatic findings were classified into three groups, hemorrhagic, fibrotic, and inflammatory lesions, and the incidence of each type of lesion was enumerated. In males, both the total and individual incidence of pancreatic lesions increased age dependently in the naïve group. EB treatment significantly decreased the total incidence at twenty-six weeks. This alteration consisted of fibrotic and inflammatory lesions, but not hemorrhagic lesions. Additionally, the incidence of hemorrhagic lesions was at the same level between male naïve and male EB groups at twelve weeks, despite a markedly higher concentration of serum estradiol in the EB group. In females, a similar tendency was seen, and the total incidence was generally low in the naïve group, whereas it was increased by OVX. OVX plus EB treatment tended to decrease the incidence accompanied by a marked increase in estradiol concentrations. In conclusion, estrogen was shown to inhibit the development of pancreatic islet lesions toward inflammation and fibrosis but did not inhibit the occurrence of hemorrhagic lesions.

Key Words: estrogen • ovariectomy • inflammation • fibrosis • pancreatic islet

Toxicologic Pathology, Vol. 37, No. 2, 218-226 (2009)
DOI: 10.1177/0192623308329283


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