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)