Possible involvement of microglia containing cyclooxygenase-1 in the accumulation of gonadotrophin-releasing hormone in the preoptic area in female rats.
Prostaglandins (PGs), especially PGE(2), are involved in the hypothalamic control of gonadotrophin-releasing hormone (GnRH) release, acting at least in part on the terminal of GnRH axons in the median eminence. The present study aimed: (i) to clarify the role of PG(s) in regulating GnRH cell function at the level of the perikarya in the preoptic area; (ii) to determine the cyclooxygenase (COX) isozyme responsible for producing PG(s) that regulates GnRH perikarya; and (iii) to identify cell types that contain the responsible COX isozyme in female rats. A surge of luteinising hormone (LH) secretion was induced by oestrogen and progesterone in ovariectomised rats. Treatment of the rat before the LH surge with indomethacin, a nonselective COX inhibitor, or NS-398, a selective COX-2 inhibitor, did not interfere with the surge. However, treatment with indomethacin or flurbiprofen, a selective COX-1 inhibitor, significantly reduced the number of GnRH-immunoreactive cells in the preoptic area at the time of peak LH secretion during the surge. NS-398 did not affect the GnRH immunoreactivity. Double-labelled immunofluorescent histochemistry revealed COX-1 immunoreactivity in the vicinity of, but not within, GnRH containing neurones in the preoptic area. COX-2 immunoreactivity was not found in the same area. The COX-1 immunoreactivity was almost entirely localised in microglia in the preoptic area, but not in neurones or astrocytes. These results suggest that microglia in the preoptic area containing COX-1 are responsible for producing PG(s), which, in turn, facilitates the accumulation of GnRH during the gonadotrophin surge in female rats.
Adachi
S
S
Department of Physiology, St Marianna University School of Medicine, Miyamae-ku, Kawasaki, Japan.
Fujioka
H
H
Kakehashi
C
C
Matsuwaki
T
T
Nishihara
M
M
Akema
T
T
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005480:Flurbiprofen / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009578:Nitrobenzenes / Q000494:pharmacology; D010052:Ovariectomy; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004967:Estrogens; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D005480:Flurbiprofen; D007986:Luteinizing Hormone; D051545:Cyclooxygenase 1; C496513:Ptgs1 protein, rat; D007213:Indomethacin