Plasma membrane changes during corpus luteum regression

Structural and biochemical changes were examined in the plasma membrane of luteal cells during corpus luteum regression. Structural alterations as indicated by an increase in the liquid-crystalline to gel phase transition temperature and a decrease in plasma membrane fluidity were observed during luteolysis in microsomes and in plasma membranes prepared from prostaglandin F2 alpha-treated rats, when samples were examined by wide angle x-ray diffraction and fluorescence polarization. In addition, a significant increase in activity of the lipolytic enzyme phospholipase A2 appeared during incubation of plasma membrane samples and dispersed luteal cells at 40 degrees C in the presence of 1.0 mM CaCl2. Similar incubation conditions also produced a drop in human chorionic gonadotropin (hCG) binding in luteal samples from prostaglandin F2 alpha-treated rats. These results indicate that during luteolysis there are important structural changes in the plasmalemma of regressing luteal cells. These alterations appear related to an increase in phospholipase A2 activity and a decrease in hCG receptors. These modifications may account for the decrease in function during corpus luteum regression.     

Steroid hormone modulation of prostaglandin secretion in the ruminant endometrium during the estrous cycle

Prostaglandins, produced from membrane phospholipids by the action of phospholipase A2, cyclooxygenase, and specific prostaglandin synthases, are important regulators of ovulation, luteolysis, implantation, and parturition in reproductive tissues. Destruction of the corpus luteum at the end of the estrous cycle in nonpregnant animals is brought about by the pulsatile secretion of prostaglandin F(2alpha) (PGF(2alpha)) from the endometrium. It has been known for many years that progesterone, estradiol, and oxytocin are the hormones responsible for luteolysis. To achieve luteolysis, two independent processes have to be coordinated; the first is an increase in the prostaglandin synthetic capability of the endometrium and the second is an increase in oxytocin receptor number. Although progesterone and estradiol can modulate the expression of the enzymes involved in prostaglandin synthesis, the primary reason for the initiation of luteolysis is the increase in oxytocin receptor on the endometrial epithelial cells. Results of many in vivo studies have shown that progesterone and estradiol are required for luteolysis, but it is still not fully understood exactly how these steroid hormones act. The purpose of this article is to review the recent data related to how progesterone and estradiol could regulate (initiate and then turn off) the uterine pulsatile secretion of PGF(2alpha) observed at luteolysis.     

Effect of exogenous prostaglandin and/or estrogen on luteolysis after electrocauterization of the largest follicles at the end of the bovine estrous cycle

In cows, electrocauterization of large follicles at the end of the luteal phase, lengthened the life span of corpora lutea. Injection of 5 mg of estradiol valerate or of 1 mg of an analogue of prostaglandin F(2alpha) induced luteolysis; however, the injection of estrogen was associated with precocious estrus without either ovulation or corpus luteum growth. Injection of both estradiol valerate and prostaglandin analogue gave the same results as estradiol valerate alone. Deferred luteolysis, observed after electrocauterization of large follicles, seemed to be due to the withdrawal of estrogens and the consequent lack of prostaglandin F(2alpha) production.     

Luteolytic action of 15-keto prostaglandin F2alpha in the rhesus monkey.

The naturally-occurring metabolite of prostaglandin F2alpha, 15-keto prostaglandin F2alpha (15-keto PGF2alpha), elicited rapid and sustained declines in serum progesterone concentrations when administered to rhesus monkeys beginning on day 22 of normal menstrual cycles. Evidence for luteolysis of a more convincing nature was obtained in studies where a single dose of 15-keto PGF2alpha was given on day 20 of ovulatory menstrual cycles in which intramuscular injections of hCG were also given on days 18-20; serum progesterone concentrations fell precipitously in monkeys within 24 hours following intramuscular administration of 15-keto PGF2alpha. However, corpus luteum function was impaired in only 4 of 11 early pregnant monkeys when 15-keto PGF2alpha was administered on days 30 and 31 from the last menses, a time when the ovary is essential for the maintenance of pregnancy. Gestation failed in 2 additional monkeys 32 and 60 days after treatment with 15-keto PGF2alpha, but progressed in an apparently normal manner in the remaining 5 animals. Two pregnant monkeys treated with 15-keto PGF2alpha on day 42 from the last menstrual period, a time when the ovary is no longer required for gestation, continued their pregnancies uneventfully. Corpus luteum function was not impaired in 9 control monkeys which received injections of vehicle or hCG at appropriate times during the menstrual cycle or pregnancy.     

Prostaglandin biosynthesis and its regulation in the bovine endometrium: A comparison between nonpregnant and pregnant status

Prostaglandin F(2alpha) (PGF(2alpha)), an arachidonic acid metabolism product of the prostaglandin synthetase pathway, is synthesized and released from the endometrium during luteolysis in nonpregnant animals. When proper conception occurs, the synthesis and release pattern is changed to maintain the corpus luteum (CL) function. The biosynthesis of prostaglandins in the bovine endometrium was highest in the microsomes but of low order. In nonpregnancy, the formation of prostaglandins from labelled precursor acid was higher than in pregnancy. Besides the prostaglandin synthetase, an inhibiting activity on the conversion of arachidonic acid to prostaglandins was found in both the nonpregnant and pregnant endometrium. During luteolysis (Day 17), a low inhibiting capacity was seen in comparison with other days of the estrous cycle (Days 1, 4 and 14). The inhibitory capacity was very high on Days 16 to 20, 25, and 31 of pregnancy. In the nonpregnant endometrium at Day 17, a very low inhibitor potency, calculated as IC(50) values, was found both in the cytoplasma and in the microsomes, whereas during early pregnancy (Days 17, 18, and 20) both cytoplasma and microsomes possessed very high inhibitor potency. This finding indicates that the bovine endometrium contains both prostaglandin synthetase and an unknown potent inhibitor of prostaglandin biosynthesis that regulates prostaglandin biosynthesis both during the estrous cycle and early pregnancy.     

An intra-corpus luteum site for the luteolytic action of prostaglandin F2 alpha in the rhesus monkey

It has not been possible to demonstrate prostaglandin F2 alpha (PGF2 alpha) participation in primate luteolysis under conditions of systemic administration or of acute intraluteal injection. These study designs were hampered by the short biological half-life in the first instance and brevity of administration in the latter. In this study, luteolysis has resulted from chronic, intraluteal delivery of PGF2 alpha. Using the Alzet osmotic pump-cannula system, normally cycling rhesus monkeys were continuously infused, until menses occurred, with PGF2 alpha (10 ng/1/hr) directly into the corpus luteum (CL, n = 6), into the stroma of the ovary not bearing the corpus luteum (NCL, n = 3), or subcutaneously (SC, n = 5). An additional 5 monkeys received vehicle (V) into the corpus luteum. All experiments commenced 5-7 days after the preovulatory estradiol surge. Luteal function was assessed by the daily measurements of plasma progesterone, estradiol, and LH. Intraluteal PGF2 alpha caused premature functional luteolysis in all monkeys, as reflected by a highly significant decline in circulating progesterone and estradiol and the early onset of menstruation, when compared to the other groups. V, NCL, and SC infusions had no effect on either circulating steroid levels or luteal phase lengths. None of the experimental groups showed any change in plasma LH concentrations. These are the first data to indicate that PGF2 alpha can induce functional luteolysis in the primate, and the site of action appears to be the corpus luteum.     

Progesterone and 15-Keto-13,14-Dihydroprostaglandin F2α Levels in Peripheral Circulation After Intrauterine Iodine Infusions in Cows

The effect of intrauterine iodine infusion on estrous cycle length was studied in four cows. The infusions were performed at various times of the estrous cycle: early, middle, late, and during luteolysis. Blood samples were drawn every third hour from the jugular vein. Progesterone and 15-keto-13,14-dihydroprostaglandin F2α (the main metabolite of PGF2α) were measured to monitor luteal activity and prostaglandin release. No release of prostaglandins was observed immediately following intrauterine infusion. Infusion in two cows on day 5 of the estrous cycle resulted in prostaglandin release after 54 and 69 hrs., respectively, followed by luteal regression and the occurrence of estrus at approx. five days after infusion. Infusions performed on days 11 or 12 resulted in prostaglandin release after 147 and 120 hrs., respectively, followed by luteolysis and heat after a 19 day estrous cycle. Infusion in two cows at days 16 and 17 resulted in prostaglandin release after 117 hrs. in both animals. One cycle was prolonged whereas the other cycle was normal in duration. One cow infused on day 20 following the occurrence of the first prostaglandin surge had a cycle length of 26 days, whereas another cow infused on day 20 was not affected because luteolysis was essentially complete by the time of infusion. One animal infused on day 5 did not respond to the iodine infusion. In this animal, however, the corpus luteum was not completely developed prior to the infusion. From this study it can be concluded: 1) intrauterine iodine infusions performed after the development of a progesterone secreting corpus luteum result in prostaglandin release within three to six days with the subsequent occurrence of luteolysis; 2) luteolysis wras in all cases observed in connection with prostaglandin F2α release of the same order of magnitude and duration as during normal luteolysis. kw|Keywords|k]prostaglandin release; k]progesterone; k]cow; k]es trous cycle; k]iodine infusion     

Changes in prostaglandin secretion by the regressing bovine corpus luteum

Secretion of prostaglandins (PGs) by the regressing corpus luteum (CL) was investigated in the cow. Six cows were implanted with microcapillary dialysis membranes of a microdialysis system (MDS) into the CL during Days 8-9 (Day 0 = estrus), and a prostaglandin (PG) F2alpha analogue (Estrumate) was injected intramuscularly (i.m.) to induce luteolysis. Acute increases in intraluteal release of PGF2alpha and PGE2 were observed during the first 4 h, followed by decreases over the next 8 h. Intraluteal release of both PGs gradually increased again during the period 48-72 h. Concentrations of PGF2alpha in ovarian venous plasma (OVP) were 4-13 times higher than those of jugular venous plasma (JVP) (P < 0.001) during the period of the experiment, and increased from 24 h after treatment with Estrumate (P < 0.05). Cyclooxygenase (COX)-2 mRNA expression increased (P < 0.05) at 2 and 24 h after treatment with Estrumate. The results indicated that local release of PGF2alpha and PGE2, and COX-2 mRNA expression were increased by Estrumate in the regressing CL at the later stages of luteolysis. Thus, luteal secretion of PGs may be involved in the local mechanism for structural rather than functional luteolysis.     

Dynamics of circulating progesterone concentrations before and during luteolysis: a comparison between cattle and horses

The profile of circulating progesterone concentration is more dynamic in cattle than in horses. Greater prominence of progesterone fluctuations in cattle than in horses reflect periodic interplay in cattle between pulses of a luteotropin (luteinizing hormone; LH) and pulses of a luteolysin (prostaglandin F2alpha; PGF2alpha). A dose of PGF2alpha that induces complete regression of a mature corpus luteum with a single treatment in cattle or horses is an overdose. The overdose effects on the progesterone profile in cattle are an immediate nonphysiological increase taking place over about 30 min, a decrease to below the original concentration, a dose-dependent rebound 2 h after treatment, and a progressive decrease until the end of luteolysis. An overdose of PGF2alpha in horses results in a similar nonphysiological increase in progesterone followed by complete luteolysis; a rebound does not occur. An overdose of PGF2alpha and apparent lack of awareness of the rebound phenomenon has led to faulty interpretations on the nature of spontaneous luteolysis. A transient progesterone suppression and a transient rebound occur within the hours of a natural PGF2alpha pulse in cattle but not in horses. Progesterone rebounds are from the combined effects of an LH pulse and the descending portion of a PGF2alpha pulse. A complete transitional progesterone rebound occurs at the end of preluteolysis and the beginning of luteolysis and returns progesterone to its original concentration. It is proposed that luteolysis does not begin in cattle until after the transitional rebound. During luteolysis, rebounds are incomplete and gradually wane. A partial rebound during luteolysis in cattle is associated with a concomitant increase in luteal blood flow. A similar increase in luteal blood flow does not occur in mares.     

Evidence for a role of prostaglandins in the antepartum release of relaxin in the pregnant rat

The relationship of the antepartum elevation in serum relaxin levels in pregnant rats to luteolysis was examined by determining the effects of the luteolysin prostaglandin F2 alpha (PGF2 alpha) and the prostaglandin synthetase inhibitor indomethacin on antepartum serum relaxin levels, as well as on luteolysis and birth. Intravenous administration of PGF2 alpha on the morning of Day 20 elevated serum relaxin levels approximately fourfold within 15 min. Administration of the prostaglandin synthetase inhibitor indomethacin from Day 19 until Day 23 protracted luteolysis, delayed or prevented birth, and delayed the antepartum elevation of serum relaxin levels, until after indomethacin treatment had been terminated. Collectively, these results indicate that prostaglandins, in particular PGF2 alpha, may promote the antepartum increase in serum relaxin levels, as well as luteolysis and birth in rats.     

Temporal associations among pulses of 13,14-dihydro-15-keto-PGF2alpha, luteal blood flow, and luteolysis in cattle

Luteal blood flow was studied in heifers by transrectal color-Doppler ultrasound. Data were normalized to the decrease in plasma progesterone to <1 ng/ml (Day 0 or Hour 0). Blood flow in the corpus luteum (CL) was estimated by the percentage of CL area with color flow signals. Systemic prostaglandin F2alpha (PGF) treatment (25 mg; n=4) resulted in a transient increase in CL blood flow during the initial portion of the induced decrease in progesterone. Intrauterine treatment (1 or 2 mg) was done to preclude hypothetical secondary effects of systemic treatment. Heifers were grouped into responders (luteolysis; n=3) and nonresponders (n=5). Blood flow increased transiently in both groups; induction of increased blood flow did not assure the occurrence of luteolysis. A transient increase in CL blood flow was not detected in association with spontaneous luteolysis when examinations were done every 12 h (n=6) or 24 h (n=10). The role of PGF pulses was studied by examinations every hour during a 12-h window each day during expected spontaneous luteolysis. At least one pulse of 13,14-dihydro-15-keto-PGF2alpha (PGFM) was identified in each of six heifers during the luteolytic period (Hours -48 to -1). Blood flow increased (P<0.02) during the 3-h ascending portion of the PGFM pulse, remained elevated for 2 h after the PGFM peak, and then decreased (P<0.03) to baseline. Results supported the hypothesis that CL blood flow increased and decreased with individual PGFM pulses during spontaneous luteolysis.     

Regulation of intraluteal production of prostaglandins

There is clear evidence for intraluteal production of prostaglandins (PGs) in numerous species and under a variety of experimental conditions. In general, secretion of PGs appears to be elevated in the early corpus luteum (CL) and during the period of luteolysis. Regulation of intraluteal PG production is regulated by a variety of factors. An autoamplification pathway in which PGF-2alpha stimulates intraluteal production of PGF-2alpha has been identified in a number of species. The mechanisms underlying this autoamplification pathway appear to differ by species with expression of Cyclooxygenase-2 (Cox-2) and activity of phospholipase A2 acting as important physiological control points. In addition, a number of other responses that are induced by PGF-2alpha (decreased luteal progesterone, increased endothelin-1, increased cytokines) also have been found to increase intraluteal PGF-2alpha production. Thus, regulation of intraluteal PG production may serve to initiate or amplify physiological signals to the CL and may be important in specific aspects of luteal physiology particularly during luteal regression.     

Prostaglandin E1 and F2alpha specific binding in bovine corpora lutea: comparison with luteolytic effects.

Preliminary characterization indicated the presence of separate prostaglandin (PG)E1 and (PG)F2alpha binding sites in membrane fractions prepared from bovine corpora lutea. These differ in the rate and temperature dependence of the specific binding. Equilibrium binding data indicate the apparent dissociation constants as 1.32 x 10(-9)M and 1.1 x 10(-8)M for PGE1 and PGF2alpha, respectively. Competition of several natural prostaglandins for the PGE1 and PGF2alpha bovine luteal specific binding sites indicates specificity for the 9-keto or 9alpha-hydroxyl moiety, respectively. Differences in relative ability to inhibit 3H-PG binding were found due to sensitivity to the absence or presence of the 5, 6-cis-double bond as well. Bovine luteal function was affected following treatment of heifers with 25 mg PGF2alpha as measured by reduced estrous cycle length, decreased corpus luteum size and significantly decreased plasma progesterone levels. In contract, treatment with 25 mg PGE1 resulted in cycle lengths comparable to those of non-treated herdmates with no apparent modification in corpus luteum size. However, plasma progesterone levels were increased significantly following PGE1 treatment compared to pretreatment values. In so far as data obtained in vitro on PGF2alpha relative binding affinity to the bovine CL can be compared to data obtained independently in vitro on PGF2alpha induced luteolysis in the bovine, PGF2alpha relative binding to the CL and luteolysis appeared to be associated. By similar reasoning, there was no apparent relationship between PGE1 relative binding affinity in the luteal fractions and luteolysis in estrous cyclic cattle.     

Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat

We investigated the expression and cell localization of NOTCH1, NOTCH4, and the delta-like ligand DLL4 in corpus luteum (CL) from pregnant rats during prostaglandin F2alpha (PGF2alpha)-induced luteolysis. We also examined serum progesterone (P(4)) and CL proteins related to apoptosis after local administration of the notch inhibitor N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT). Specific staining for NOTCH1 and NOTCH4 receptors was detected predominantly in large and small luteal cells. Furthermore, in line with the fact that the notch intracellular domain is translocated to the nucleus, where it regulates gene expression, staining was evident in the nuclei of luteal cells. In addition, we detected diffuse cytoplasmic immunostaining for DLL4 in small and large luteal cells, in accordance with the fact that DLL4 undergoes proteolytic degradation after receptor binding. The mRNA expression of Notch1, Notch4, and Dll4 in CL isolated on Day 19 of pregnancy decreased significantly after administration of PGF2alpha. Consistent with the mRNA results, administration of PGF2alpha to pregnant rats on Day 19 of pregnancy decreased the protein fragment corresponding to the cleaved forms of NOTCH1/4 CL receptors. In contrast, no significant changes were detected in protein levels for the ligand DLL4. The local intrabursal administration of DAPT decreased serum P(4) levels and increased luteal levels of active caspase 3 and the BAX:BCL2 ratio 24 h after the treatment. These results support a luteotropic role for notch signaling to promote luteal cell viability and steroidogenesis, and they suggest that the luteolytic hormone PGF2alpha may act in part by reducing the expression of some notch system members.     

Identical changes in Bax expression, but not Fas ligand expression, occur in structural luteolysis in gonadotropin releasing hormone agonist- and prolactin-treated superovulated rats

Structural luteolysis induced by gonadotropin releasing hormone agonist (GnRHa) or prolactin (PRL) is defined as histological involution of the corpus luteum. We reported that one of the mechanisms of structural luteolysis induced by PRL was tissue remodeling by matrix metalloproteinase (MMP) and also apoptosis in superovulated rats. We also reported that GnRHa induced structural luteolysis with elevation of MMP. In this study, we investigated whether GnRHa caused apoptosis in mature corpus luteum of superovulated rats and also examined the expression of apoptosis-related molecules (Fas, Fas ligand (FasL), Bcl-2, Bax). We gave 4-day GnRHa treatment 5 days after hCG injection to immature female rats treated with pregnant mare surum gonadotrophin (PMSG) and hCG to induce structural involution of mature corpus luteum. PMSG-hCG-treated rats without GnRHa treatment, rats treated with bromocryptine (Brom) to induce functional luteolysis and rats treated with Brom followed by PRL (Brom+PRL) to mimic the PRL surge to induce structural luteolysis as we previously reported were used for comparison. GnRHa treatment caused structural luteolysis characterized by structural involution, a decrease in the serum progestin level, and apoptotic bodies as well as structural luteolysis induced by Brom+PRL. FasL expression in corpora lutea was elevated after Brom treatment, but there was no elevation of FasL after GnRHa treatment started. FasL expression decreased and Bax expression increased in structural luteolysis induced by GnRHa as well as Brom+PRL treatment, although Fas and Bcl-2 expression did not change throughout the luteal phase. In summary, both GnRHa and Brom+PRL caused structural luteolysis, one of whose mechanisms was apoptosis with an increase in Bax expression, but not with an identical change in FasL expression. It is speculated that the significance in alteration of FasL may involve some mechanism other than apoptosis.     

Progesterone receptor is not required for progesterone action in the rat corpus luteum of pregnancy

In this study, we investigated whether progesterone exerts a local action regulating the function of the corpus luteum of pregnancy in rats. The luteal activities of the enzymes 3beta-hydroxysteroid dehydrogenase (3beta-HSD), involved in progesterone biosynthesis, and 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD), that catabolizes progesterone and reduces progesterone secretion by the corpus luteum, were evaluated after intrabursal ovarian administration of progesterone in pregnant rats that had received a luteolytic dose of prostaglandin F2alpha (PGF2alpha). Luteal 3beta-HSD activity decreased and 20alpha-HSD activity increased after PGF2alpha treatment (100 microg x 2 intraperitoneally on Day 19 of pregnancy at 12:00 p.m. and 4:00 p.m.) when compared with controls sacrificed at 8:00 p.m. on Day 20 of pregnancy. This effect of PGF2alpha on the luteal 3beta-HSD and 20alpha-HSD activities was abolished in animals that also received an intraovarian dose of progesterone (3 microg/ovary on Day 19 of pregnancy at 8:00-9:00 a.m.). In a second functional study, luteal cells obtained from 19-day pregnant rats responded to the synthetic progestin promegestone (R5020) in a dose-dependent manner, with an increase in the progesterone output. In addition, the glucocorticoid agent hydrocortisone did not affect progesterone accumulation in the same luteal cell culture. We also examined by immunocytochemistry the expression of progesterone receptors (PR) in the corpora lutea during pregnancy and demonstrated the absence of PR in this endocrine gland in all the days of pregnancy studied. In the same pregnant rats, positive staining for PR was observed in cells within the uteroplacental unit, such as cells of the decidua basalis and trophoblast giant cells of the junctional zone. In addition, positive PR staining was observed in the ovarian granulosa and theca cells of growing follicles, but not in corpora lutea of ovaries obtained from cycling rats at proestrus. In summary, this report provides further evidence of a local action of progesterone regulating luteal function in the rat despite the absence of a classic PR.     

Counter current transfer of PGF2 alpha in the mesometrial vessels as a mechanism for prevention of luteal regression in early pregnancy

A new concept has been presented on the mechanism protecting the corpus luteum during oestrous cycle, early pregnancy and pseudopregnancy induced by oestrogens. The concept is based on the recently discovered mechanism of back transfer of prostaglandin F2 alpha from the broad ligament vasculature into the uterus and on the participation of oestrogen in this process. The morphological facilitates for counter-current transfer of PGF2 alpha in the area of mesometrial vasculature and ability the uterus to bind PGF2 alpha were presented. It has been concluded that the process of PGF2 alpha back-transfer from mesometrial vasculature into the uterus may reduce in uterine venous blood the amplitude of PGF2 alpha pulses and by this way may reduce the penetration of prostaglandin into subovarian area and from there to the corpus luteum.     

In vivo levels of prostaglandin F2 alpha, E2 and prostacyclin in the corpus luteum of pregnant and pseudopregnant rats

Prostaglandin F2 alpha (PGF2 alpha) is a well-known luteolytic factor in the rat corpus luteum. To investigate a possible luteal origin of PGF2 alpha, measurements of this prostaglandin were performed in different luteal tissues in vivo. Prostaglandin E2 (PGE2) and the stable metabolite of prostacyclin, 6-keto-PGF1 alpha, were assayed simultaneously. Corpora lutea of different ages from 57 pregnant and pseudopregnant rats (mated with sterile males) were rapidly excised, dissected in 0 degree C indomethacin solution, homogenized, and extracted for prostaglandins with solid-phase extraction cartridges. Prostaglandins were determined by radioimmunoassay. Plasma levels of progesterone and 20 alpha-dihydroprogesterone were also monitored. In the adult pseudopregnant rat model, luteolysis occurs at Day 13 +/- 1, and maximal levels of all three prostaglandins were detected on Day 13 of pseudopregnancy: 0.40 +/- 0.02, 2.6 +/- 0.29, and 1.76 +/- 0.24 pmol/mg protein (mean +/- SEM, n=7) for PGF2 alpha, PGE2, and 6-keto-PGF1 alpha respectively. In pregnant rats, on the corresponding day, levels were considerably lower: 0.15 +/- 0.02, 0.90 +/- 0.13, and 0.50 +/- 0.06 pmol/mg protein (mean +/- SEM, n=9, p less than 0.0001), respectively. Luteal levels in pregnant rats showed a continuous decline on Days 13 and 19 for all prostaglandins measured, whereas in pseudopregnant rats an increment of PGF2 alpha was noted between Days 7 and 13 and remained high on Day 19. PGE2 closely followed levels of PGF2 alpha, but at a 5- to 10-fold higher level. The coefficient of correlation between PGF2 alpha and PGE2 in the luteal compartment of both models was 0.87 (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)