Phenanthrenequinone disrupts progesterone production in rat luteal cells.
The ability of the environmental contaminant phenanthrene (PH) and its photooxidized product phenanthrenequinone (PHQ) to disrupt progesterone secretion was examined in a model system of in vitro suspensions of luteal cells from the rat. Treatment with PHQ dramatically inhibited luteinizing hormone (LH) stimulated progesterone secretion. PHQ also generated a significant increase in reactive oxygen species (ROS). In the absence of LH, however, PHQ stimulated a small increase in basal progesterone secretion. The parent compound, PH, did not alter progesterone or ROS release. Since there is evidence that PHQ lowers the activity of nitric oxide synthase (NOS) and that nitric oxide (NO) affects progesterone production, we examined the response to the NOS inhibitors N-monomethyl-L-arginine, Zn protoporphyrin-9, and aminoguanidine in luteal cells. However, there was no effect of these agents on LH stimulated progesterone secretion. These results indicated that PHQ is a potent disrupter of progesterone secretion and should perhaps be considered in assessing the risk of PH to humans.
Nykamp
J A
JA
Biology Department, University of Waterloo, N2L 3G1, Waterloo, Ontario, Canada.
Bols
N C
NC
Carlson
J C
JC
D000818:Animals; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006727:Hormone Antagonists / Q000633:toxicity*; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D010616:Phenanthrenes / Q000633:toxicity*; D011374:Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013480:Superovulation; D019323:omega-N-Methylarginine / Q000494:pharmacology
D006146:Guanidines; D006727:Hormone Antagonists; D010616:Phenanthrenes; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; C017803:zinc protoporphyrin; D019323:omega-N-Methylarginine; C005399:9,10-phenanthrenequinone; C031181:phenanthrene; D011374:Progesterone; C002385:linsidomine; D007986:Luteinizing Hormone; D008981:Molsidomine; C004479:pimagedine