Yoshihiro Waki (1), Ken-ichi Miyamoto (1,*), Shinya Yamamoto (1), Yukie
Saitoh (1), Shohei Kasugai (2) and Keiichi Ohya (2)
(1) Department of Pharmacology and Pharmaceutics, Graduate School of Natural Science and Technology, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
(2) Department of Pharmacology, Faculty of Dentistry, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549, Japan
(*) To whom correspondence should be addressed.
Abstract: When Walker 256/S carcinosarcoma (W256/S) was subcutaneously inoculated into the back of mature female Wistar Imamichi rats (10-week-old), the tumor grew rapidly and caused increases in the urinary excretions of calcium and hydroxyproline, without changes in the serum concentrations of calcium and inorganic phosphorus. Furthermore, osteoporosis-like changes in the femurs and decrease in uterus weight were observed, as previously reported for W256/S-bearing young rats. In the healthy mature female rats, the estrus cycle passed through four stages (proestrus, estrus, metestrus and diestrus) within 4 to 5 days, with a peak of serum estradiol and progesterone levels in the proestrus stage. On the other hand, after subcutaneous inoculation of W256/S into the rats, the estrus cycle tended to pause upon the metestrus or diestrus stage, accompanied with significantly low estradiol and progesterone levels in serum. W256/S tumor produced and secreted luteinizing hormone-releasing hormone (LH-RH). In conclusion, it seems that the ectopical secretion of LH-RH from the tumor resulted in the decrease in the secretion of gonadotropic hormones, following low level of sex hormones and stopping the estrus cycle. Therefore, W256/S-bearing rats may be a model for osteoporosis of hypoovarianism or postmenopause.
Keywords: Walker 256/S carcinosarcoma, Osteoporosis, Estrus cycle, Menopause, Luteinizing hormone-releasing hormone (LH-RH)