Modulatory effect of estradiol and testosterone on the development of N-nitrosodiisopropanolamine induced thyroid tumors in female rats.
Both experimental and clinical research support the conclusion that thyroid tumors are sex dependent. Also, several studies have pointed out that the use of oral contraceptives is associated with a higher risk of thyroid tumor. Most of the existing reports suggest indirect effects of sex steroids on thyroid tumor growth in women. In this work, we present data to support the direct promoting effect of estradiol and testosterone on carcinogen-induced thyroid tumorigenesis. Thyroid tumors were induced in rats by a combination of N-nitrosodiisopropanolamine (DHPN) and phenobarbital (PB) treatment. Serum thyroid hormones, thyroid stimulating hormone (TSH), steroid hormones, thyroidal steroid concentration, androgen and estrogen receptors were quantified. Serum thyroid hormones and TSH suggested euthyroid status of the all experimental animals. Ovariectomy decreased the incidence of DHPN + PB induced thyroid tumor when compared with ovary intact rats and estradiol/testosterone supplementation increased the same. Thyroidal estradiol level and its nuclear receptors increased in the tumor tissue specifically. Testosterone supplementation to DHPN-treated ovariectomized rats specifically induced the development of malignant thyroid tumors. Addition of estradiol in vitro to thyrocytes induced a higher proliferation rate. Our data proves a direct promoting role of estrogen on carcinogen-induced thyroid tumor development.
Thiruvengadam
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Department of Endocrinology, Dr. ALM.PG. Institute of Basic Medical Sciences, University of Madras, Chennai, India. athiruvengadam@yahoo.com
Govindarajulu
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Aruldhas
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D000818:Animals; D002273:Carcinogens; D004958:Estradiol / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000493:pharmacokinetics / Q000494:pharmacology*; D006728:Hormones / Q000097:blood; D015994:Incidence; D009602:Nitrosamines; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D013739:Testosterone / Q000493:pharmacokinetics / Q000494:pharmacology*; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000139:chemically induced* / Q000453:epidemiology
D002273:Carcinogens; D012739:Gonadal Steroid Hormones; D006728:Hormones; D009602:Nitrosamines; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013739:Testosterone; C012457:diisopropanolnitrosamine; D004958:Estradiol