Possible Involvement of Microglia Containing Cyclooxygenase‐1 in the Accumulation of Gonadotrophin‐Releasing Hormone in the Preoptic Area in Female Rats

Abstract

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.

Immunohistochemical evidence for the relationship between microglia and GnRH neurons in the preoptic area of ovariectomized rats with and without steroid replacement

“…Importantly, a half of microglia was not immunoreactive for COX-1, thus an anatomocal study between microglia and GnRH might be interesting. The present study confirmed COX-1 immunoreactivity in the POA: COX-1 immunoreactivity was observed in the vicinity of GnRH cells, but was not found within GnRH cells themselves, as shown in the previous study [13].…”

“…Since COX-1 immunoreactivity was not found within GnRH neurons and almost entirely doubled-labelled with CD11b, COX-1-expressing microglia would be away from GnRH neurons [13]. Importantly, a half of microglia was not immunoreactive for COX-1, thus an anatomocal study between microglia and GnRH might be interesting.…”

“…Free-floating sections were rinsed with PBS, incubated in blocking solution (2 % BSA, 0.4 % Triton X-100 in PBS) for 30 min and incubated with rabbit polyclonal anti-COX-1 (1:2000; Cayman Chemical, Ann Arbor, MI, USA), mouse monoclonal anti-CD11b (1:400; Millipore, Billerica, MA, USA) and mouse monoclonal antiGnRH (LRH13; 1:20000; generously gifted from Dr. K. approximately half of CD11b-ir cells were also positive for COX-1 immonoreactivity as previously reported [13]. COX-1 immunoreactivity was also found in the vicinity of GnRH neurons in the POA of OVX rats as in ovarian steroid-primed OVX rats.…”

“…We have recently performed double-labeled immunohistochemical studies, and found abundant COX-1 immunoreactivity in the vicinity of, but not within, GnRH neurons in the POA of female rats at the time of gonadotropin surge [13]. COX-2 was not detected in the same area, suggesting a predominant role of COX-1.…”

Differential Gene Expression in Gonadotropin-Releasing Hormone Neurons of Male and Metestrous Female Mice

“…GnRH neurons have been shown to receive neuronal information from several basic neurotransmitter systems of the brain [11,12]. They also communicate with microglia and astroglia [13,14,15,16] and process remote metabolic signals originating from different peripheral tissues/organs of the body [17,18,19]. Events that interfere with the pulsatile secretion of GnRH [20] inhibit reproduction [21,22,23,24].…”