Intraluteal infusion of a prostaglandin synthesis inhibitor, sodium meclofenamate, causes premature luteolysis in rhesus monkeys.
The physiological significance of locally produced prostaglandins (PGs) in the regulation of the functional lifespan of the primate corpus luteum is unknown. In the current study, the PG synthesis inhibitor sodium meclofenamate was administered to adult female rhesus monkeys beginning in the midluteal phase of the menstrual cycle. Meclofenamate was infused continuously for 7 days into the corpus luteum (100 micrograms/h, n = 6) or the jugular vein (100 micrograms/h, n = 3; 1000 micrograms/h, n = 3) via osmotic minipump. As controls, PBS was infused into the corpus luteum (n = 7) or jugular vein (n = 5). In some of the monkeys receiving intraluteal infusions, chronic aortic and utero-ovarian venous catheters were implanted, and blood samples were collected on alternate days for the measurement of PGE and PGF2 alpha by RIA. Saphenous venous blood was collected daily, and progesterone and cortisol levels were determined by RIA. LH levels were determined by the mouse Leydig cell bioassay. Progesterone levels over 5 days preceding treatment were not different among groups. A decline in progesterone levels on day 1 after surgery was observed in all treatment groups and was accompanied by a 1-day elevation in cortisol levels. Thereafter, five of seven monkeys who received intraluteal infusions of PBS displayed normal progesterone patterns during treatment and normal luteal phase lengths of 15.4 +/- 1.2 days (mean +/- SEM). In six monkeys that received intraluteal infusions of meclofenamate, progesterone levels typically fell to less than 1 ng/ml within 72 h after initiation of infusion; progesterone levels during 7 days of intraluteal infusion were significantly lower (P less than 0.01) in meclofenamate- vs. PBS-treated monkeys. Meclofenamate infusion into the corpus luteum significantly shortened (P less than 0.01) the luteal phase to 10.5 +/- 1.0 days. In contrast, progesterone levels during 7 days of meclofenamate infusion into the jugular vein did not differ from those in PBS-treated monkeys, and the length of the luteal phase was unaltered. LH levels, measured daily, did not differ among groups either before or during treatment. Although an venous/arterial gradient in PGE was detected at the time of surgery, we were unable to detect a significant gradient across the ovary in PGE or PGF2 alpha at any time after surgery in monkeys treated with either PBS or meclofenamate. The present data suggest an obligatory luteotropic role for locally produced metabolites of arachidonic acid, but a physiological role for either PGE or PGF2 alpha in regulating the primate corpus luteum remains equivocal.
Sargent
E L
EL
Department of Physiology, University of Arizona, Tucson 85724.
Baughman
W L
WL
Novy
M J
MJ
Stouffer
R L
RL
D000818:Animals; D003338:Corpus Luteum / Q000187:drug effects / Q000502:physiology*; D015237:Dinoprost / Q000097:blood; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D007260:Infusion Pumps; D008183:Luteal Phase / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood; D008253:Macaca mulatta; D008469:Meclofenamic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D010053:Ovary / Q000098:blood supply; D011374:Progesterone / Q000097:blood; D011448:Prostaglandin Antagonists; D011453:Prostaglandins / Q000502:physiology*; D011458:Prostaglandins E / Q000097:blood; D014599:Uterus / Q000098:blood supply; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011458:Prostaglandins E; D062367:ortho-Aminobenzoates; D008469:Meclofenamic Acid; D011374:Progesterone; D007986:Luteinizing Hormone; D015237:Dinoprost; D006854:Hydrocortisone