Effects of carbamazepine on the first ovulation in gonadotropin-primed immature female rats.
1. The effects of carbamazepine (CBZ) and its possible mechanisms on the first ovulation were investigated in immature female rats. The first ovulation was induced by administration of equine chorionic gonadotropin (eCG) at 0800 h at 26 days of age. 2. A single s.c. injection of 360 mg x kg(-1) CBZ at 1300 h on the first pro-oestrus (day 28) completely inhibited the first ovulation on the morning of day 29. A marked elevation in 13, 14-dihydro-prostaglandin F2alpha (13, 14H2-PGF2alpha) forming capacity, a sensitive indicator of luteinizing hormone (LH) surge, was not detected in the CBZ-treated group at 0800 h on day 29 (72 h after eCG treatment). The elevation in serum LH levels at 57 h after eCG treatment was not observed in the CBZ-treated group, either. The blocking of the first ovulation and 13, 14H2-PGF2alpha forming capacity were recovered by an i.p. injection of human CG on day 28 in all animals. 3. However, the first ovulation was not blocked by repeated injections of 360 mg x kg(-1) CBZ at 1300 h once daily for 3 days (days 26 - 28). The repeated injections of CBZ caused a great fall (64% decrease) in the serum levels of CBZ at 4 h after the final CBZ injection as compared with the case of a single injection of CBZ and resulted in a delay for 5 h the occurrence of LH surge, which is normally observed around 57 h after eCG injection. 4. A significant increase in the activity of microsomal CBZ catabolism by the repeated injections of CBZ was quantitatively verified by the HPLC analysis. But, the activity of CBZ metabolism in the single injected-animals showed almost similar levels to that in the control. 5. The present results demonstrated that a single injection of CBZ blocks the ovulation by inhibiting LH surge but that the failure of the inhibition of ovulation by repeated injections of CBZ is due to a decrease in serum CBZ levels mediated through CBZ-induced hepatic enzyme induction.
Tamura
K
K
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392, Japan.
Yatabe
Y
Y
Sakamoto
H
H
Hosokawa
M
M
Kobayashi
K
K
Chiba
K
K
Kogo
H
H
D000818:Animals; D002220:Carbamazepine / Q000494:pharmacology*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D006736:Horses; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects*; D011359:Proestrus / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011974:Receptors, LH / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D011974:Receptors, LH; C026527:13,14-dihydroprostaglandin F2alpha; D002220:Carbamazepine; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D015237:Dinoprost