Patterns of gonadotrophin secretion associated with ovulation

A detailed analysis was made of circulating luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin throughout the estrous cycle in rats. Vaginal cytology was recorded daily for 18 or 23 days in 2 groups of adult female rats, 300 and 400 per group. The presence of distended uteri or tubal ova was noted at the time of exsanguination under ether anesthesia. Serum concentrations of LH, FSH, and prolactin were determined by radioimmunoassay. In 404 rats with regular 5-day cycles, all 3 hormones reached maximum concentrations on the afternoon of functional proestrus. During the next 3 days FSH decreased progressively, and LH levels indicated a diurnal fluctuation with minimum concentrations during darkness. Serum prolactin may have b een elevated due to anesthesia and exsanguination and showed a rapid increase which occurred simultaneously with elevated LH and FSH on the afternoon of proestrus. Radioimmunoassay of all 3 hormones indicated that the increases in serum LH and prolactin did not necessarily occur simultaneously. Hypophysectomy and sequential heart puncture of proestrus rats during maximum hormone release showed disappearance rates (half-lives) for LH, FSH, and prolactin of 20, 110, and 13 minutes, respectively.     

Hypothalamic and pituitary effects of prostaglandins on ACTH secretion

Various prostaglandins (PGs) were tested for their effects on ACTH secretion upon injection into the anterior pituitary, basomedial hypothalamus, basolateral hypothalamus, or a tail vein in anesthetized female rats. In some experiments, the PGs were injected in combination with a CRF preparation. The greatest effect seen was the stimulation of ACTH (and presumably CRF) secretion exerted at the basomedial hypothalamus. At the anterior pituitary, the PGs alone were without effect, but they did decrease the magnitude of the response to subsequent CRF.     

Hypothalamic and pituitary effects of prostaglandins on ACTH secretion.

Various prostaglandins (PGs) were tested for their effects on ACTH secretion upon injection into the anterior pituitary, basomedial hypothalamus, basolateral hypothalamus, or a tail vein in anesthetized female rats. In some experiments, the PGs were injected in combination with a CRF preparation. The greatest effect seen was the stimulation of ACTH (and presumably CRF) secretion exerted at the basomedial hypothalamus. At the anterior pituitary, the PGs alone were without effect, but they did decrease the magnitude of the response to subsequent CRF.     

Interrelationships between prostaglandins, cyclic AMP and steroids in ovulation.

Ovulation is a complex phenomenon, involving a series of biochemical events within the ovary, leading to the rupture of the follicle. This paper summarizes recent studies in our laboratory of some of these biochemical changes using the rabbit as an experimental model. It has been shown in our laboratory that isolated Graafian follicles obtained from oestrous rabbits synthesize steroids and cyclic AMP when incubated in vitro. Luteinizing hormone added to the incubation medium increased steroidogenesis and cyclic AMP synthesis many fold. When follicles were isolated from rabbits at different times following the ovulatory stimulus (mating or HCG injection) it was found that the in vitro response to LH in terms of steroidogenesis and cylcic AMP synthesis was lost as ovulation approached. In contrast, when prostaglandins (PGF and PGE) were measured in rabbit Graafian follicles it was found that the PGF and PGE levels increased as ovulation approached. From these data and from reports in the literature, we have developed a hypothetical model for ovulation in the rabbit which may help in a better understanding of the ovulatory process.     

Synergistic interaction between prostaglandins and paf-acether in experimental animals and man

Platelet activating factor (PAF-acether) is released from a variety of inflammatory cell types and has properties appropriate to a mediator of allergy and inflammation. Here, we have examined the interaction between PAF-acether and the prostaglandins, PGE2 and ZK 36374 (a stable analogue of prostacyclin, PGI2) in the skin of guinea-pigs and human volunteers. PGE2 and ZK36374 significantly potentiated increased plasma protein extravasation induced by PAF-acether in guinea-pigs, assessed by extravasation of I-125-HSA. In addition, PGE2 significantly potentiated the ability of PAF-acether to elicit acute wheal (volume) and flare responses in human skin. The inflammatory properties of PAF-acether should not be considered in isolation since this phospholipid interacts synergistically with prostaglandins which are recognised as modulators of inflammation.     

Synergistic interaction between prostaglandins and PAF-acether in experimental animals and man

Platelet activating factor (PAF-acether) is released from a variety of inflammatory cell types and has properties appropriate to a mediator of allergy and inflammation. Here, we have examined the interaction between PAF-acether and the prostaglandins, PGE2 and ZK 36374 (a stable analogue of prostacyclin, PGI2) in the skin of guinea-pigs and human volunteers. PGE2 and ZK 36374 significantly potentiated increased plasma protein extravasation induced by PAF-acether in guinea-pigs, assessed by extravasation of I-125-HSA. In addition, PGE2 significantly potentiated the ability of PAF-acether to elicit acute wheal (volume) and flare responses in human skin. The inflammatory properties of PAF-acether should not be considered in isolation since this phospholipid interacts synergistically with prostaglandins which are recognised as modulators of inflammation.     

Effects of an LHRH antagonist on gonadotrophin and oestradiol secretion, follicular development, oestrus and ovulation in Holstein heifers

Mature cyclic Holstein heifers were given a luteolytic dose of cloprostenol followed by two i.v. injections, 12 h apart, of various doses of [Ac-D-Nal1, D-p-Cl-Phe2, D-Trp3, D-Arg6, D-Ala10]-LHRH, beginning either at the time of first observation of behavioural oestrus, or 48 h after the cloprostenol injection. When treatment began at the first observation of oestrus, the time of ovulation, as determined by ultrasonic echography, was significantly delayed by total doses of 0.8 mg or more of the antagonist. When given at 48 and 60 h after cloprostenol injection, a total dose of 1.5 mg of the antagonist significantly delayed the growth of the ovulating follicle, the onset of oestrus, the preovulatory surges of oestradiol, LH and FSH, and ovulation. It is concluded that the LHRH antagonist can effectively suppress endogenous LH secretion and may therefore be useful in the study of follicular development, ovulation, and other events in the oestrous cycle of the cow.     

Multiple sites of interaction between prostaglandins and non-steroidal anti-inflammatory agents

Several non-steroidal anti-inflammatory agents (NSAIA) are shown to inhibit the net production of prostaglandin (PG)- like activity from arachidonic acid by a cell-free preparation of guinea-pig lung. Moreover, these agents also antagonize PGE₁-induced contractions of the isolated gerbil colon. The anti-spasmogenic effects are reversible and specific. At high concentrations, indomethacin and mefenamic acid interfere with the binding of PGE₁ to a broken cell preparation of rat epididymal adipocytes. Taken together the data indicate that NSAIA interact with prostaglandins at multiple sites and are consistent with the suggestions reported previously that NSAIA may have multiple actions.     

Diversification of cyclooxygenase-2-derived prostaglandins in ovulation and implantation

Previous observations of ovulation and fertilization defects in cyclooxygenase-2 (COX-2)-deficient mice suggested that COX-2-derived ovarian prostaglandins (PGs) participate in these events. However, the specific PG and its mode of action were unknown. Subsequent studies revealed that mice deficient in EP(2), a PGE(2)-receptor subtype, have reduced litter size, apparently resulting from poor ovulation but more dramatically from impaired fertilization. Using a superovulation regimen and in vitro culture system, we demonstrate herein that the ovulatory process, not follicular growth, oocyte maturation, or fertilization, is primarily affected in adult COX-2- or EP(2)-deficient mice. Furthermore, our results show that in vitro-matured and -fertilized eggs are capable of subsequent preimplantation development. However, severely compromised ovulation in adult COX-2- or EP(2)-deficient mice is not manifested in immature (3-wk-old) COX-2- or EP(2)-deficient mice, suggesting that the process of ovulation is more dependent on PGs in adult mice. Although the processes of implantation and decidualization are defective in COX-2(-/-) mice, our present results demonstrate that these events are normal in EP(2)-deficient mice, as determined by embryo transfer and experimentally induced decidualization. Collectively, previous and present results suggest that whereas COX-2-derived PGE(2) is essential for ovulation via activation of EP(2), COX-2-derived prostacyclin is involved in implantation and decidualization via activation of peroxisome proliferator-activated receptor delta.     

Effects of indomethacin and prostaglandins on ovulation of goldfish

A technique is described whereby elevated temperature and HCG injection yield a high percentage of ovulation in gravid goldfish. Indomethacin (10 μg/g; i.p. injection) completely inhibits ovulation if given within 6 hours following HCG (4 IU/g); the unovulated oocytes develop rapidly into corpora atretica. PGE₁, PGE₂, and PGF_2α (5 μg/g; i.p. injection) induce ovulation in fish treated with indomethacin and HCG; PGE₂ was most effective when given 11 hours after HCG. The results suggest that the ovulatory action of prostaglandins following HCG stimulation is at the level of the ovary and that it is restricted to a period between 7 and 12 hours after the gonadotropin injection.     

Multiple sites of interaction between prostaglandins and non-steroidal anti-inflammatory agents.

Several non-steroidal anti-inflammatory agents (NSAIA) are shown to inhibit the net production of prostaglandin (PG)- like activity from arachidonic acid by a cell-free preparation of guinea-pig lung. Moreover, these agents also antagonize PGE-1-induced contractions of the isolated gerbil colon. The anti-spasmogenic effects are reversible and specific. At high concentrations, indomethacin and mefenamic acid interfere with the binding of PGE-1 to a broken cell preparation of rat epididymal adipocytes. Taken together the data indicate that NSAIA interact with prostaglandins at multiple sites and are consistent with the suggestions reported previously that NSAIA may have multiple in vivo actions.