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PubMed1988

Studies on the mechanism of ovulation using the model of the isolated ovary.

Using the isolated perfused rabbit and rat ovaries as experimental models, we have studied various biochemical aspects of the ovulatory process. In rabbits, ovulations were induced by injecting hCG prior to the perfusion or by adding LH directly to the medium. In PMSG-treated rats, ovulations were induced by adding LH to the perfusion system. Steroids and other metabolites were analyzed in the perfusate and in follicular fluid. Steroid levels in follicular fluid were high early in the preovulatory development, but declined to very low levels 4 hours after LH stimulation. Levels of prostaglandins E and F rose as ovulation approached. In both perfusion models, indomethacin blocked ovulation without affecting steroid release or oocyte maturation. In the rabbit, PGF2 alpha reversed the indomethacin-induced inhibition and was able to induce follicular rupture by itself. Manipulations of the follicular fluid content of progesterone and estradiol to supraphysiological levels did not affect follicular rupture or oocyte maturation in the rabbit model. When the initial increase in LH-induced steroidogenesis was blocked by a 3 beta-ol-dehydrogenase inhibitor, ovulation was not affected. In rats, inhibition of estradiol production by an aromatase blocker did not affect the ovulatory process. When the endogenous formation of cyclic AMP is increased by pretreatment with a phosphodiesterase inhibitor, the LH-induced ovulation frequency increases in rabbits. Furthermore, forskolin, which increased the adenylate cyclase activity, stimulated steroidogenesis and induced follicular rupture. Recent experiments in the rat indicate that cyclic AMP acts on the ovulatory process via an effect on prostaglandin synthesis.

Animals↗

PubMed1969

The action of chlormadinone acetate (6-chloro-delta6-dehydro-17alpha-acetoxyprogesterone) upon experimentally induced ovulation in the rabbit.

1. The ovulation response to electrical stimulation of the median eminence, or to the intrapituitary infusion of median eminence extract, was observed in control rabbits and animals pre-treated with chlormadinone acetate.2. Chlormadinone acetate pre-treatment did not significantly reduce the proportion of rabbits ovulating in response to electrical stimulation. However, there was a significant reduction in the average number of ruptured follicles when compared with the animals in the control group.3. Chlormadinone acetate pre-treatment significantly reduced the proportion of animals ovulating in response to the intrapituitary infusion of median eminence extract as compared with the control series. However, there was no significant reduction in the average number of ruptured follicles (in those rabbits that ovulated) when compared with the control groups.4. Chlormadinone acetate pre-treatment produced no significant effect upon either the proportion of animals ovulating, or the average number of ruptured follicles, following I.V. injection of 50 mug LH.5. The conclusion drawn is that chlormadinone acetate blocks copulattion-induced ovulation in the rabbit by action at a site in the central nervous system located above the median eminence. The possible effects of chlormadinone acetate upon the secretion of FSH, the pituitary sensitivity to releasing factors and the ovarian sensitivity to LH are discussed.

Animals↗

PubMed1989

The involvement of platelet activating factor in ovulation.

Follicle rupture during ovulation is associated with inflammation-like changes. Because platelet activating factor (PAF) participates in the inflammatory process, the effect of a PAF-specific antagonist, BN52021, on the ovulatory response was tested in rats. BN52021, administered locally, inhibited follicle rupture in rats stimulated to ovulate with human chorionic gonadotropin (hCG). In addition to suppressing rupture of the follicles, this antagonist suppressed the hCG-stimulated increase in ovarian collagenolysis and vascular permeability. The inhibition of ovulation of BN52021 could be reversed by simultaneous administration of PAF. Furthermore, PAF partially reversed the blockage of ovulation by inhibitors of eicosanoid synthesis. Collectively, these results suggest the involvement of PAF in ovulation. Its role seems to be closely related to the metabolism of arachidonic acid. Thus, modulation of PAF action may serve as an additional target for regulation of reproduction via its action on ovulation.

Animals↗

PubMed1975

Attempts to programme ovulation with exogenous oestrogens and LH-RH analogue.

An attempt was made to programme ovulation in women on a predetermined day of the menstrual cycle by treatment used to induce ovulation in anovulatory sterility. At laparotomy for elective sterilization the ovaries were observed to assess the occurrence of ruptured follicles and ovulation. Histological analysis of ovaries and endometrium was performed, and ova were recovered from some women. Several regimens were tested but ovulation seldom occurred as planned. Clomiphene citrate, human chorionic gonadotrophin (HCG), synthetic luteinizing hormone releasing hormone (LH-RH), and ethinyloestradiol were ineffective. Human menopausal gonadotrophin followed by HCG was more effective, but multiple ovulations occurred. When one single injection of a potent long-acting LH-RH analogue was given on day 13 of the cycle to 10 women pretreated with ethinyloestradiol signs of recent ovulation were observed on day 15 in seven and on day 16 in two.

Administration, Intranasal↗

PubMed1998

Blockage of gonadotropin-induced first ovulation caused by thyroidectomy and its possible mechanisms in rats.

To determine the role of the thyroid gland on the ovarian functions during the initiation process of puberty, we examined the effects and its mechanisms of hypothyroidism on the first ovulation induced by equine chorionic gonadotropin (eCG) in immature female rats. Animals were thyroidectomized on day 22 and were injected with 5 IU of eCG on day 26 to induce the first ovulation on day 29. The number of antral follicles that secrete inhibin and the ovarian weight were significantly increased in thyroidectomized rats (Tx rats) 48 h after eCG treatment compared with those in non-Tx rats. However, thyroidectomy (Tx) significantly suppressed the rates of ovulating animals on day 29. The blockage of ovulation in Tx rats was recovered by administration of human chorionic gonadotropin or luteinizing hormone (LH)-releasing hormone (LHRH) on day 28. Inhibition of serum LH (not follicle-stimulating hormone) levels induced by Tx was almost restored to control levels by injection of LHRH. A significant increment in prolactin levels in Tx rats was also observed on day 28. The present data indicate that Tx before puberty in female rats causes the blockage of the first ovulation and that the inhibitory effects on ovulation are mainly due to the reduction in the preovulatory LH surge, which is partially mediated through an inhibition of LHRH action on the secretion of LH.

Animals↗

PubMed2004

Tumor necrosis factor-alpha-induced matrix proteolytic enzyme production and basement membrane remodeling by human ovarian surface epithelial cells: molecular basis linking ovulation and cancer risk.

The majority of cancer is of surface/cyst epithelial origin. The ovarian surface epithelial cells are organized by a sheet of basement membrane composed mainly of collagen IV and laminin, and it is believed that the basement membrane greatly influences the physiological properties of ovarian surface epithelial cells. Previous studies in our laboratories indicated that loss of the basement membrane, an obligated step in ovulation, is also a critical step during the morphological transformation and tumor initiation of the ovarian surface epithelium. It is speculated that the loss of basement membrane in ovarian surface epithelial transformation may have similar biological mechanism to the loss of surface epithelial basement membrane in ovulation. However, the mechanisms involved in the ovarian surface epithelial basement membrane removal during ovulation are still not completely understood. In the current study, cultured human ovarian surface epithelial (HOSE) cells were examined for their abilities to produce matrix hydrolyzing enzymes and degrade basement membrane in response to a number of potential local mediators in ovulation. Among the candidate-stimulating factors tested, tumor necrosis factor (TNF)-alpha and IL-1beta (to a lesser extent) were found to drastically increase urokinase type plasminogen activator (uPA) and matrix metalloproteinase (MMP)-9 activities secreted from HOSE cells. MMP-2, the other major HOSE cell-secreted gelatinase, is constitutively produced but not regulated. As demonstrated by immunofluorescence staining and Western blot analysis, TNF-alpha treatment caused the degradation and structural reorganization of collagen IV and laminin secreted and deposited by HOSE cells in culture. Amiloride, an uPA inhibitor, not only inhibited the activity of uPA but was also able to suppress TNF-alpha-stimulated MMP-9 activity and prevented the TNF-alpha-stimulated remodeling of the basement membrane extracellular matrix, suggesting the contribution of uPA-mediated proteolytic cascade in this process. This study implicates the potential roles of TNF-alpha, uPA, and MMP-9 in ovarian surface epithelial basement membrane degradation and remodeling, which are processes during ovulation and may contribute to epithelial transformation. The findings may underscore the importance of TNF-alpha, uPA, and MMP-9 in ovarian surface epithelial basement membrane remodeling and may provide a molecular mechanism linking ovulation and ovarian cancer risk.

Amiloride↗

PubMed1977

Ovulation induced by LH-RH in rats made anovulatory by various experimental procedures.

The injection of LH-RH induced ovulation in constant estrous rats (CEA), made anovulatory either by frontal hypothalamic deafferentation (FHD), or by exposure to continuous light (CL), or by neonatal androgenization (NA) with 0.500 mg testosterone propionate (NA500). Rats neonatally treated with 1.250 mg testosterone (NA1250) were almost unable to ovulate. 100% of FHD-CEA rats ovulated in response to 10 ng LH-RH, which is 1/3 of the lowest dose able to determine 100% of full ovulation in control proestrous rats. NA500-CEA rats, on the other hand, ovulated in response to doses comparable to those effective in the controls, whereas in CL-CEA rats the doses required for full ovulation were 2-3 times higher than in the controls. The results of these experiments demonstrate that the pituitary glands of CEA rats respond to the stimulation by the specific hypothalamic releasing factor. The pituitary response, however, appears enhanced in FHD-CEA rats and markedly depressed in CL-CEA animals.

Animals↗

PubMed1979

LH release and ovulation in the rat following depletion of hypothalamic norepinephrine: chronic vs. acute effects.

The effects of long-term hypothalamic norepinephrine (NE) depletion on reproductive cyclicity, ovulation, and luteinizing hormone (LH) release were studied in adult female rats. Bilateral transections of the ascending noradrenergic pathway (ANP) at the level of the mesencephalon led to an 83% depletion of hypothalamic NE. Although some animals exhibited a period of acyclicity following this surgical procedure, by 23 days all animals had begun to cycle. When checked for ovulation at around 40 days, all of the rats had shed full quotas of ova. There was no significant difference in either the timing or magnitude of the surge when proestrous LH levels in NE-depleted rats were compared with sham transected controls. To see if the residual hypothalamic NE left after transection of the ascending noradrenergic pathway was important for maintenance of normal LH secretion and ovulation, a group of long-term depleted rats were given an NE synthesis inhibitor (diethyldithiocarbamate: DDC). In all of the sham-cut and intact control rats this drug either partially or completely blocked ovulation, but it was effective in only 40% of the depleted animals. The other 60% not only ovulated, but shed full quotas of ova. These results demonstrate that normal LH secretion can occur even when hyplthalamic NE levels are extremely low. Although acute depressions of NE by pharmacological agents such as DDC effectively block the LH surge, this inhibition is not sustained when NE is depleted over long periods of time. Therefore, NE apparently plays a modulatory, rather than mandatory, role in control of LH release and ovulation.

Animals↗

PubMed1986

Effect of various hypothalamic deafferentations injuring different parts of the GnRH pathway on ovulation, GnRH content of the median eminence, and plasma LH and FSH levels.

Various supra- and retrochiasmatic cuts injuring different parts of the septo-preoptico-infundibular GnRH pathway were made in adult female rats, and their effects on ovulation, median eminence (ME) GnRH content and on plasma LH and FSH levels were studied. Extended retrochiasmatic frontal cut just behind the optic chiasm, or a frontal cut in front of the suprachiasmatic nucleus presumably interrupting the whole GnRH pathway blocked ovulation, led to persistent estrus with polyfollicular ovaries, and reduced the ME GnRH content to 10 and 32%, respectively, expressed in percentage of unoperated control value. Severance of the GnRH pathway on one side or partial interruption of the pathway on the two sides in the retrochiasmatic area did not interfere with ovulation, and the ME GnRH content was 50% or more of the control value. Disconnection of the GnRH fibers coming from the septum resulted in a more than 30% decrease in the GnRH content of the ME, but did not block ovulation. Two separate symmetrical lateral cuts in the suprachiasmatic area leaving intact the presently known GnRH pathway reduced the ME GnRH content to 40% of the intact value, but did not interfere with ovulation. Plasma LH and FSH levels of the animals with different knife cuts were considerably dissociated and there were no apparent correlations between brain interventions and the concentrations of these two hormones in the blood. Our previous findings together with the present data suggest that: half of the GnRH pathway, medial or lateral bundles of the pathway on the two sides are sufficient for ovulation and cyclic gonadotrophic function; persistent estrus develops if the ME GnRH content is below 40% of the control value, and about 60% of the ME GnRH originates outside the preoptic, supra- and retrochiasmatic region. Half of this 60% may come from the septum and the vertical part of the diagonal band of Broca, the other half from the region in front of the preoptic area. The remaining 40% presumably arises from the preoptic (7-10%), supra- (15-20%) and retrochiasmatic region (8-10%).

Animals↗

PubMed1982

Basal body temperature as a method of ovulation detection: comparison with ultrasonographical findings.

In 47 cycles with hormonal evidence of ovulation, the detection and timing of ovulation by basal body temperature (BBT) and by ultrasonographical observation are compared. The ovulation detection rate by ultrasonographical method proves to be considerably higher than by BBT criteria. The timing of the day of ovulation is evaluated, assuming that the ultrasonographical event of follicle disappearance represents ovulation. BBT criteria nadir, coverline and the eye-balling method show a very poor frequency distribution. The result of the FDHP method is a nearly symmetrical distribution, however, with a considerable range. We conclude that ovulation detection and timing by BBT are not reliable.

Body Temperature↗

PubMedDate not supplied

Segregation of a major gene influencing ovulation in progeny of Lacaune meat sheep.

Inheritance of the ovulation rate (OR) in the Lacaune meat breed was studied through records from a small nucleus of 36 hyper-prolific ewes screened on farms on the basis of their natural litter size, and from progeny data of three selected Lacaune sires. These sires were chosen at the AI centre according to their breeding values estimated for the mean and the variability of their daughters' litter size. Non-carrier Lacaune dairy ewes were inseminated to produce 121 F1 daughters and 27 F1 sons. Twelve sons (four from each sire) were used in turn to inseminate non-carrier Lacaune dairy ewes providing 260 BC progeny ewes. F1 and BC progeny were brought from private farms and gathered after weaning on an experimental farm where ovulation rates were recorded in the first and second breeding seasons. With an average of 6.5 records each, the mean OR of hyper-prolific ewes was very high (5.34), and 38.4% of records showed a rate of 6 or more. F1 data showed high repeatability of OR (r = 0.54) within ewe, with significant variability among ewes. High OR (> or = 4) were observed in each family. A segregation analysis provided a significant likelihood ratio and classified the three founders as heterozygous. BC ewes also displayed high repeatability of OR (r = 0.47) and the mean OR varied considerably between families (from 1.24 to 1.78). Seven of the 12 BC families presented high-ovulating ewes (at least one record > or = 4) and segregation analysis yielded a highly significant likelihood ratio as compared to an empirical test distribution. The high variability of the mean ovulation rate shown by a small group of daughters of BC ewes inseminated by putative carrier F1 rams, and the very high ovulation rate observed for some of these ewe lambs, confirmed the segregation of a major gene with two co-dominant alleles borne by an autosome. The difference between homozygous non-carriers and heterozygous ewes was about one ovulation on the observed scale and 2.2 standard deviations on the underlying scale.

Animals↗

PubMed2002

Activation of the kinin system in the ovary during ovulation: role of endogenous progesterone.

BACKGROUND: Previous work by our group and others has implicated a role for kinins in the ovulatory process. The purpose of the present study was to elucidate whether endogenous progesterone, which is an intraovarian regulator of ovulation, might be responsible for induction of the kinin system in the ovary during ovulation. The gonadotropin-primed immature rat was used as the experimental model, and the role of endogenous progesterone was explored using the antiprogestin, RU486. RESULTS: The results of the study revealed that RU486 treatment, as expected, significantly attenuated ovulation. Activity of the kinin-generating enzyme, kallikrein, was elevated in the ovary in control animals prior to ovulation with peak values observed at 4 h post hCG, only to fall to low levels at 10 h, with a recovery at 20 h post hCG. RU486 treatment had no significant effect on ovarian kallikrein activity as compared to the control group. Total ovarian kininogen levels in control animals increased significantly at 12-14 h after hCG - coinciding with initiation of ovulation. Thereafter, ovarian kininogen levels fell to low levels at 20 h, only to show a rebound from 24-38 h post-hCG. RU486 treatment had no significant effect on the rise of total ovarian kininogen levels from 12-14 h after hCG; however, from 30-40 h post hCG, RU486-treated animals had significantly higher total ovarian kininogen levels versus control animals, suggesting that endogenous progesterone may act to restrain elevations of kininogens in the post-ovulatory ovary. This robust elevation of ovarian kininogen levels by RU486 was found to be primarily due to an increase in T-kininogen, which is a potent cysteine protease inhibitor. CONCLUSIONS: Taken as a whole, these results suggest that endogenous progesterone does not regulate kallikrein activity or kininogens prior to ovulation, but may provide a restraining effect on T-kininogen levels in the post-ovulatory ovary.

Animals↗

PubMed2006

Recombinant versus highly-purified, urinary follicle-stimulating hormone (r-FSH vs. HP-uFSH) in ovulation induction: a prospective, randomized study with cost-minimization analysis.

BACKGROUND: Both recombinant FSH (r-FSH) and highly-purified, urinary FSH (HP-uFSH) are frequently used in ovulation induction associated with timed sexual intercourse. Their effectiveness is reported to be similar, and therefore the costs of treatment represent a major issue to be considered. Although several studies about costs in IVF have been published, data obtained in low-technology infertility treatments are still scarce. METHODS: Two hundred and sixty infertile women (184 with unexplained infertility, 76 with CC-resistant polycystic ovary syndrome) at their first treatment cycle were randomized and included in the study. Ovulation induction was accomplished by daily administration of rFSH or HP-uFSH according to a low-dose, step-up regimen aimed to obtain a monofollicular ovulation. A bi- or tri-follicular ovulation was anyway accepted, whereas hCG was withdrawn and the cycle cancelled when more than three follicles greater than or equal to 18 mm diameter were seen at ultrasound. The primary outcome measure was the cost of therapy per delivered baby, estimated according to a cost-minimization analysis. Secondary outcomes were the following: monofollicular ovulation rate, total FSH dose, cycle cancellation rate, length of the follicular phase, number of developing follicles (>12 mm diameter), endometrial thickness at hCG, incidence of twinning and ovarian hyperstimulation syndrome, delivery rate. RESULTS: The overall FSH dose needed to achieve ovulation was significantly lower with r-FSH, whereas all the other studied variables did not significantly differ with either treatments. However, a trend toward a higher delivery rate with r-FSH was observed in the whole group and also when results were considered subgrouping patients according to the indication to treatment. CONCLUSION: Considering the significantly lower number of vials/patient and the slight (although non-significant) increase in the delivery rate with r-FSH, the cost-minimization analysis showed a 9.4% reduction in the overall therapy cost per born baby in favor of r-FSH.

Adult↗

PubMed2003

Tissue-type plasminogen activator and its inhibitor plasminogen activator inhibitor type 1 are coordinately expressed during ovulation in the rhesus monkey.

Ovulation is a gonadotropin-controlled process that is essential for the propagation of all mammalian species. In the present study, we used a pregnant mare serum gonodotropin/human chorionic gonadotropin (hCG)-induced, synchronized ovulation model in rhesus monkeys and systematically investigated the roles of the plasminogen activator (PA) system in the ovulatory process of the primate. At different follicular developmental stages throughout the periovulatory period, samples of ovaries, granulosa cells, and theca-interstitial cells as well as follicular fluid were collected, and levels of PA and PA inhibitor type-1 (PAI-1) were evaluated by fibrin overlay, reverse fibrin overlay, Northern blot analysis, and in situ hybridization, respectively. We showed that in response to an injection of ovulation-triggering hCG, which mimics the preovulatory surge of LH in the circulation, granulosa cell-derived tissue-type PA (tPA) was substantially elevated in preovulatory follicles and reached its maximum level just before ovulation. Although theca-interstitial cell-derived PAI-1 was also stimulated by pregnant mare serum gonodotropin and hCG treatments, however, the maximum level of PAI-1 appeared 12 h earlier than that of tPA. When ovulation approached, accompanying the highest tPA level in the preovulatory follicles, the follicular PAI-1 level declined dramatically to its minimum value. Moreover, our data on the expression of follicular PA and PAI-1 over the periovulatory period were reinforced by results obtained at the mRNA level. Our data suggest that the coordinated expression of tPA and PAI-1 may be of importance for the follicular rupture process during ovulation in the primate.

Aging↗

PubMed1984

Hourly administration of luteinizing hormone induces ovulation in prepubertal female sheep.

This investigation examined the effects of repeated injections of LH on ovarian function in the immature sheep approximately 12 weeks before the time of the first expected spontaneous ovulation. The frequency of endogenous LH pulses during the pretreatment period was approximately one pulse each 3 h. The first experiment determined that rapid injection (iv) of 15.5 micrograms LH replicated the amplitude of endogenous pulses. Hourly injection of this dose for 48 h to simulate the rapid LH pulse frequency of the follicular phase of the postpubertal female induced a LH surge and ovulation in two of three lambs. By contrast, administration of 33% of the dose over the 48-h period did not [5.2 micrograms/h (three lambs) or 15.5 micrograms each 3 h (three lambs)]. The second experiment (seven lambs) determined the time course of the preovulatory estradiol rise produced in response to hourly LH pulses (15.5 micrograms/injection), as well as the length of the luteal phase after the induced LH surge. Four lambs produced a sustained estradiol rise, a LH surge, and ovulation. The luteal phase was normal (13 days) in one and short in three lambs (6-11 days). In the remaining three prepubertal females that did not ovulate in response to 48-h injections of LH, the estradiol rise was not sustained. Circulating estradiol in five untreated control lambs exhibited only transient increases during the course of the study. The results indicate that hourly administration of physiological quantities of LH over a relatively brief period (48 h) can produce a follicular phase culminating in first ovulation in the immature lamb. In the context of the mechanism proposed for puberty in the female sheep, the findings are consonant with the hypothesis that the hypothalamus, through its modulation of LH pulse frequency, governs the initiation of ovulation.

Animals↗

PubMed1985

Follicular plasminogen activator: involvement in ovulation.

Production of plasminogen activator (PA) by granulosa cells (GC) and its stimulation by gonadotropins led to the suggestion that PA is involved in ovulation. However, whereas only LH may be regarded as the ovulation-inducing hormone in the rat, FSH was found to be much more potent than LH in enhancing PA production by GC. Assuming that the entire follicular wall, rather than isolated GC, is involved in follicular rupture, we have examined activity of PA in intact follicles. LH (NIH-LH-S23) was 5-fold more potent than FSH (NIH-FSH-S14), and purified ovine LH and FSH were equally potent in enhancing follicular PA activity. Furthermore, injection into the ovarian bursa of proestrous rats of epsilon-amino-caproic acid and benzamidine (0.05-0.25 mmol), inhibitors of serine proteases, including PA and plasmin, resulted in a dose-dependent inhibition of ovulation without causing changes discernible by histological examinations of the ovaries. Whereas steroids did not change basal follicular PA production in culture, addition of estradiol-17 beta [(E2) 1 microgram/ml] but not progesterone or testosterone, further enhanced LH-stimulated PA. Aminoglutethimide phosphate (10(-3) M) and 17 beta-formamidoandrost-4-en-3-one inhibited LH-induced increase in follicular PA and this inhibition was reversed by addition of E2. Intrabursal injection of indomethacin, an inhibitor of cyclooxygenase, and of nordihydroguaiaretic acid, an inhibitor of lipoxygenase pathway of arachidonic acid metabolism at doses which effectively blocked ovulation (0.3 mg/bursa) had no effect on PA content of the follicles. Likewise, indomethacin (10 microM) and nordihydroguaiaretic acid (100 microM) did not affect LH-stimulated PA in vitro. In conclusion, LH, the physiological trigger of ovulation is, at least, as potent as FSH in stimulating follicular PA activity. The role of serine proteases, most probably of PA and plasmin, in ovulation is further corroborated by a pharmacological approach. LH stimulation of follicular PA appears to be enhanced by E2 but is not mediated by arachidonic acid metabolites.

Animals↗

PubMed1985

The involvement of collagenolysis in ovulation in the rat.

Collagenolytic activity in ovarian follicles was previously demonstrated by using synthetic peptides and reconstituted collagen fibers. However, attempts to demonstrate degradation of ovarian collagen and to correlate collagenase activity with ovulation were not successful. By administration of L-(5-3H) proline, we have labeled ovarian and follicular collagen and followed collagenolytic activity by separation of 3H-hydroxyproline (3H-Hyp) from acid hydrolyzates of ovarian tissue by HPLC. The level of ovarian and follicular 3H-Hyp decreased by about 40% on the afternoon of proestrus or after exogenous stimulation of ovulation by human CG (hCG), and this decrease was abolished by blocking the surge of gonadotropins with Nembutal. To verify that the observed reduction in 3H-Hyp was due to the action of a typical collagenase, the collagenous fraction was prepared from ovarian tissue and from preovulatory follicles before and after the ovulatory stimulus. The extracts were treated with trypsin (25 min, 25 C, 0.01 mg/ml) plasmin and p-amino-phenyl-mercuric acetate to fully activate the collagenase extracted along with collagen. Both, enzymatic and chemical activation of collagenase in vitro resulted in degradation of collagen. This degradation could be inhibited by cysteine and EDTA; both are classic inhibitors of mammalian collagenases. The activity of ovarian collagenase increased within 3 h after hCG-stimulation, peaked at 5-fold 6 h after hCG, and declined afterwards. Administration of cysteine (0.001-0.01 mmol) into the bursal cavity of proestrous rats blocked ovulation and breakdown of ovarian collagen in a dose-dependent manner. Cysteine effectively inhibited ovulation even when injected 7 h after the hCG stimulus. Inhibitors of arachidonic acid metabolism prevent ovulation. Indomethacin (inhibitor of cyclooxygenase) and nordihydroguaiaretic acid (inhibitor of lipoxygenase) blocked ovulation and inhibited hCG-induced ovarian collagenolysis. Collectively, these results corroborate the essential role of collagenolysis in follicular rupture in mammals.

Aminocaproic Acid↗

PubMed1988

The effects of bradykinin on ovulation and prostaglandin production by the perfused rabbit ovary.

Involvement of the vasoactive peptide bradykinin (BK) in ovulation, oocyte maturation, and prostaglandin (PG) production was assessed using an in vitro perfused rabbit ovary preparation. In the first experiment, BK at a concentration of 0.033, 0.33, or 3.3 micrograms/ml was added to the perfusate of one ovary at hourly intervals for the first 10 h of perfusion. The contralateral control ovary was treated with medium alone parallel to the experimental ovary. Ovaries were perfused for a total of 12 h. BK induced ovulation in the absence of gonadotropin in a dose-related fashion, but did not induce maturation of ovulated ova or follicular oocytes. BK significantly stimulated PG production at all concentrations tested, but the effect was not dose related. Prostacyclin, as reflected by the concentration of 6-keto-PGF1 alpha in the perfusate, was the major PG produced. Smaller quantities of PGE2 and PGF2 alpha were present in the perfusate. After a single injection of BK (3.3 micrograms/ml), 6-keto-PGF1 alpha and PGF2 alpha production increased within 15 min and reached a maximum at 60-90 min. PGE2 did not change significantly over this time period. The addition of 1 microgram/ml indomethacin to the perfusate completely inhibited BK-stimulated PG production. However, indomethacin did not significantly affect the ovulatory efficiency of BK-treated ovaries. Neither BK nor indomethacin induced any degenerative changes in ovulated ova or follicular oocytes. The addition of a BK antagonist at 1 microgram/ml every 30 min to the perfusate resulted in an effective blockade of hCG-induced ovulation. These results suggest that BK is involved in the process of follicle rupture, but BK may induce ovulation by a mechanism(s) other than through PG stimulation.

6-Ketoprostaglandin F1 alpha↗