Inhibition of rat ovarian [3H]thymidine uptake by luteinizing hormone-releasing hormone agonists: a possible mechanism for preventing damage by cytotoxic agents.
To investigate the mechanism involved in luteinizing hormone-releasing hormone (LHRH) agonists' protective effects against chemotherapy-induced ovarian damage, female rats were either implanted with 1-mg pellets of LHRH agonist Zoladex (LHRHz) or sham operated. All rats were implanted with osmotic minipumps loaded with [3H]thymidine 48 h before sacrifice in diestrus. Ovaries were combusted in a biological material oxidizer. Tritiated water was recovered in a special cocktail, and ovarian tritiated thymidine uptake (3HTU) was calculated. In five experiments, LHRHz significantly reduced ovarian 3HTU. This was observed 5 days after implanting LHRHz pellets. Ovarian 3HTU correlated significantly with serum estradiol, LH, and ovarian and uterine weights. Autoradiography showed that almost all ovarian 3HTU is by granulosa cells. These data suggest that LHRHz suppresses ovarian mitotic activity. Since cytotoxic agents preferentially destroy rapidly dividing cells, our findings may represent a mechanism for ovarian protection.
Ataya
K M
KM
Department of Obstetrics and Gynecology, Wayne State University, School of Medicine, Detroit, Michigan 48201.
Palmer
K C
KC
Blacker
C M
CM
Moghissi
K S
KS
Mohammad
S H
SH
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002064:Buserelin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004958:Estradiol / Q000097:blood; D005260:Female; D017273:Goserelin; D007986:Luteinizing Hormone / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000493:pharmacokinetics*
D017273:Goserelin; D004958:Estradiol; D007986:Luteinizing Hormone; D002064:Buserelin; D013936:Thymidine