Effect of human chorionic gonadotrophin and indomethacin on ovulation, steroidogenesis and prostaglandin synthesis in preovulatory follicles of PMSG-primed immature rats

Abstract

Summary. Immature rats were treated with PMSG followed 56 h later by 10 i.u. hCG. Follicles were removed at intervals after hCG injection. Transient increases in progesterone, testosterone and oestradiol synthesis were first evident 1 h after hCG, but values peaked at 3\p=n-\5h and returned to control levels by 10 h. Increased synthesis of PGE-2 and PGF-2\g=a\was not evident until 3 h and peaked at more than 10 h after hCG. Ovulation began between 8 and 10 h after hCG and 83% of animals had ovulated within 12 h. Doses of90 or 1800 \ g=m\ g indomethacin given together with hCG substantially inhibited ovulation and PG synthesis, but only the higher dose inhibited the hCG-induced elevation of progesterone and testosterone synthesis; hCG-induced oestradiol synthesis was not affected by either dose of indomethacin.We conclude that the peak of PG synthesis after hCG treatment related closely to the timing of ovulation; the steroidogenic response to hCG was not blocked by doses of indomethacin sufficient to inhibit synthesis of PGE-2 and PGF-2\g=a\ by more than 80%.

Effects of Indomethacin on the Selective Release of Follicle-Stimulating Hormone during the Period of Ovulation in the Rat.

“…Although there are many evidences that indicates unruptured luteinized follicles exposed to an ovulation-inhibiting dose of indomethacin continue to secrete normal amounts of progesterone (reviewed in [6]), the concurrent injection of indomethacin and hCG to eCG-primed immature rats completely suppresses the immediate progesterone release after hCG treatment and reduces the number of oocytes shed [20]. The present study can not explain the reason why the effects of indomethacin on the immediate release of progesterone after hCG treatment are different between experiments, however, differences of the timing to initiate luteinization may be involved in this discrepancy, since high dose of indomethacin inhibits ovulation and progesterone secretion, but low dose inhibits only ovulation, when the compound was administered subcutaneously at 1 hr prior to hCG injection in eCG-stimulated immature rats [22].…”

“…Several reports indicate the involvement of PGs in the regulation of hypothalamic-pituitary axis, such that PGE 2 acts mainly at the median eminence to evoke GnRH [22], that PGs stimulate LH release from the pituitary in vivo [31,39] and in vitro [30], and that pretreatment with indomethacin reduces these effects of PGs on hypothalamicpituitary axis [32]. On the other hand, indomethacin decreased peripheral levels of inhibin during the period of eguine chorionic gonadotropin (eCG)-stimulated and -non stimulated folliclular development in immature rats [12][13][14] with an increase of peripheral FSH level [13].…”

Relationship between the production of prostaglandins and progesterone by luteinizing human granulosa cells

“…Increased generation of these inflammatory mediators has been implicated in follicular rupture and ovulation of the mature oocyte (Grinwich et al 1972, Espey 1980, Richardson 1986, Munalulu et al 1987. However, the significance of locally synthesized prostaglandins in the paracrine/autocrine control of ovarian steroidogenesis has yet to be established.…”

Clomiphene citrate inhibits gonadotropin-induced ovulation by reducing cyclic adenosine 3′,5′-cyclic monophosphate and prostaglandin E2 levels in rat ovary

“…Both steroidogenesis and PGE 2 biosynthesis take place in theca, granulosa, and surrounding stromal cells (2)(3)(4). The gonadotropins induce steroidogenesis in follicular cells by cyclic adenosine 3=,5=-cyclic monophosphate (cAMP)-mediated pathway to stimulate growth, development, and maturation of preovulatory follicles (5)(6)(7).…”