The herbal medicine Tokishakuyakusan increases fetal blood glucose concentrations and growth hormone levels and improves intrauterine growth retardation induced by N(omega)-nitro-L-arginine methyl ester.
N(omega)-Nitro-L-arginine methyl ester (L-NAME) induces a pre-eclampsia-like syndrome in pregnant rats. We have previously reported the anti-hypertensive effects of several Japanese traditional (Kampo) medicines in this model, and one of these, Tokishakuyakusan (TS), also improved intrauterine growth retardation (IUGR). In the present study, we characterized the effect of TS on IUGR. TS administration reversed the decrease in fetal body weight and fetal blood glucose concentration induced by the infusion of L-NAME. Growth hormone (GH) levels in the fetal blood, which were decreased by L-NAME infusion, were also significantly elevated by TS; however, levels of GH releasing hormone (GHRH) and insulin-like growth factor I (IGF-I) were unchanged and only slightly changed, respectively. Treatment with L-NAME with or without TS had no apparent effect on GH, GHRH, and IGF-I levels of dams. In an immunocytochemical study, the number of GH-positive cells in the fetal pituitary gland was significantly increased in TS-treated rats. These data suggest that enhanced proliferation of somatotrope cells of the pituitary gland and the resultant increase in GH secretion in the fetus may be involved in the improvement of IUGR by TS.
Tsumura Research Institute, Tsumura and Co., Ibaraki, Japan. takei_hisato@mail.tsumura.co.jp
Hisato
H
Takei
Seiichi
S
Iizuka
Masahiro
M
Yamamoto
Shuichi
S
Takeda
Masako
M
Yamamoto
Kazuyoshi
K
Arishima
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D005317:Fetal Growth Retardation / Q000188:drug therapy*; D020567:Fetal Weight / Q000187:drug effects; D013006:Growth Hormone / Q000187:drug effects; D013007:Growth Hormone-Releasing Hormone / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects; D010920:Placenta / Q000187:drug effects; D010929:Placentation; D010946:Plants, Medicinal / Q000737:chemistry; D011225:Pre-Eclampsia / Q000139:chemically induced / Q000188:drug therapy*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; C413220:toki-shakuyaku-san; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D019331:NG-Nitroarginine Methyl Ester