Acute stimulatory effects of prostaglandin F2α on serum progesterone concentrations in pregnant and pseudopregnant pigs

PROSTAGLANDINS

A C U T E S T I M U L A T O R Y EFFECTS OF P R O S T A G L A N D I N F 2 = ON S E R U M P R O G E S T E R O N E C O N C E N T R A T I O N S IN ~ R E G N A N T A N D P S E U D O P R E G N A N T PIGS ~

J.E. Gadsby 2, C.A. Smith 3 and G.W. ~Imond 3 2Dep~rtment of Anatomy, Physiological Sciences and Radiology and ~Department of Food An~m-i And Equine Medicine, College of Veterinary Medicine, North Carolina State University, Raleigh,

N.C.

27606

ABSTRACT: The objective of this study was to investigate whether PGF2a, administered to pregnant and pseudopregnant gilts in vivo, would cause an acute increase in serum progesterone concentrations nrior to luteolysis. Pregnant (n = 9) and pseudopregnant (n = 4) gilts were fitted with a jugular vein cannula on day 40, were treated with 3 ml vehicle (control) i.m. on day 42 and with 15 mg PGF2ct on day 45. Blood samples were collected at frequent (5 and 15 rain) intervals from 1 h before until 1 h after control and PGF2a injections, at 15 rain intervals for 4 h, and then at 5, 6, 9, 21, 33, 45 and 57 h post injection. Progesterone was measured by radioimmunoassay (RIA) in all samples. Porcine LH was measured by RIA in samples collected frequently in the 1 h pre- and 1 h post-injection periods. Serum progesterone concentrations were unchanged in both pregnant and pseudopregnant animals in response to control injection on day 42. However, in both pregnant and pseudopregnant gilts, PGF2ct injection on day 45 resulted in an acute increase (~75-80% above pre-treatment levels; p < 0.05) in serum progesterone lasting ~1 h, followed by a return to pre-treatment levels by 2 h, and then a decline to 1 ng/ml or less by 45-57 h (pregnant) or 21-57 h (pseudopregnant), associated with luteolysis. Serum LH concentrations were unchanged between 1 h preand post-treatment periods in response to either control or PGF2et-treatment, in both pregnant and pseuodpregnant gi.'lts. These results indicate that PGF2winjection produces a rapid and transient increase in serum progesterone concentrations which may result from a rapid and direct stimulatory action of PGF2ct on porcine luteal cell progesterone synthesis/secretion in vivo. 1 This material is based on work supportedby CSRS-USDA, under agreement No. 89-37240-4680 and by the State of North Carolina. Reprint requests to: Dr. John Gadsby, College of Veterinary Medicine, NCSU, 4700 Hillsborough, Raleigh, NC 27606.

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INTRODUCTION: Prostaglandin F2o is believed to be the physiological agent responsible for luteolysis in the pig since, (i) the concentrations (magnitude and frequency of pulses) of PGF2o in utero-ovarian vein blood increase on days 12-13 (1,2) just prior to the time of natural luteolysis, (ii) treatment with indomethacin (a cyclooxygenase inhibitor) which inhibits enodogenous prostaglandin production, delays natural luteolysis in both pregnant (3) and non-pregnant (4,5) pigs, and (iii) exogenous PGFh treatment causes luteolysis in cycling (after day 12; 6-ll), pregnant (12, 13), hysterectomized (14) and pseudopregnant (15. 16) pigs. In contrast to its luteolytic potency in vivo, PGFk has been shown to stimulate, in a dose-dependent manner, progesterone production by enzyme-dissociated pig luteal cells during short-term (4-6 h) incubations in vitro (17, Earnest and Gadsby, unpublished observations). Likewise, stimulatory effects of PGF2o in vitro on progesterone production/release by luteal tissue/cells of other species (rat, cow, human, monkey), have been reported (18-22). Since, the stimulatory effects of PGF2o on pig luteal cell progesterone production in vitro described above were observed during short-term incubations (4 - 6 h), we speculated that this apparent “luteotrophic” effect may represent an “acute” (early) response to PGF2o. If observed in vivo, this stimulatory effect would e the wellestablished luteolytic (i.e. decreased serum progesterone concentrations) actions of PGFzo, which are detectable by 4 - 12 h following PGF2o administration to the nonpregnant and pregnant pig (6, 9, 11). Indeed, there are reports documenting acute (within 0.5 - 1 h), transient, stimulatory effects of PGF2o on serum progesterone concentrations in non-pregnant cycling gilts (23, 24). and a preliminary report suggesting that a similar effect occurs in pregnant pigs (6). The objective of the present study was to investigate in detail the acute effects (on serum progesterone) of administration of PGFzo to pregnant and pseudopregnant pigs. This was of particular interest in view of the fact that in these animals, corpora lutea display an extended life-span, and which, unlike the corpora lutea of the estrous cycle, are dependent on pituitary LH-support (25). In addition, we measured serum LH concentrations during the acute phase of blood sampling, immediately before and after PGF2o injection, to determine whether elevated secretion of LH, a critical luteotrophin in these animals (25), may account for (partially or completely) any increase in serum progesterone concentrations observed during this period. MATERIALS

AND METHODS:

Animals; For Experiments 1 and 3, pubertal gilts (Yorkshire-Lax&ace) were purchased from a local supplier (N.C. Dept. of Agriculture, Cherry Unit, Goldsboro. NC) and transported to NCSU Dept. of Animal Science Unit I swine facility, where they were housed for the remainder of the study. For Experiment 2. pubertal gilts (Duroc) were obtained from NCSU Unit II swine facility and transported to Unit I prior to the beginning of the study. Estrus detection, breeding, hormone injections, cannulation and blood sampling were performed at Unit I.

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’ . A. Preguant Gdt~. Experiment I: Five gilts had estrous cycles synchronized by oral administration of 16 mg/gilt/day (for 14 days) ally1 trenbolone (Regumate@‘, Hoechst-Roussel, Somerville, NJ). Following withdrawal of ally1 trenbolone, gilts were bred (twice) on the fast and second days of estrus (first day of standing estrus = day 0). On day 40 (mean 40.2 + 0.5 days; n = 5) of pregnancy, each animal was fitted (non-surgically) with a jugularvein cannula. The cannulae were used to collect twice daily blood samples on days 4042, and were flushed after each use with sterile 3.5% citrate (in water) to prevent blood clot formation. On day 42.2 gilts (Control) were given 3 ml sterile water i.m. (at time 0) and blood samples were collected at the following times before and after injection: at 60, -45, -30, -25, -20, -15, -10, -5, 0, 5, 10, 15, 20, 25, 30, 45 and 60 (min.); and after injection, at 15 min. intervals up to 4 h, and at 5, 6, 9, 21, 33, 45 and 57 h. On day 45 (45.2 + 0.5 days; n = 5), all gilts (n = 5; PGF2o) were injected with 15 mg Prostaglandin F2o (PGF2o Tham salt; Lutalyse@, UpJohn Co., Kalamazoo, MI) i.m. and blood samples were collected at the times (before and after injection) listed above. All animals received a second injection of PGF2o (10 mg i.m.) following the 9 h blood sample to ensure complete luteolysis and termination of pregnancy. Gilts were observed at 6 h intervals for signs of abortion. Experiment 2: Gilts (n = 4) were mated (without prior synchronization regimen) on the first (once; n = 3) and second (twice; n = 1) days of estrus. Animals were cannnlated on day 40 (40 + 0.4 days; n = 4) of pregnancy. All animals were subjected to Control treatment (sterile water i.m.) on day 42 (42 + 0.4 days; n = 4) and were given 15 mg PGF2, i.m. on day 45 (45 +. 0.4 days; n = 4). Blood sample collection and other procedures were as described in Experiment 1. However, in this experiment, no second PGF2, treatment was given. B. Pseudoureenant

Gilts:

Experiment 3: Four gilts were synchronized with oral ally1 trenbolone (for 14 days; see Expt. 1) and the day of estrus following withdrawal of ally1 trenbolone was considered day 0. On days 11-15, all gilts were treated with 5 mg (per gilt) estradiol valerate (Sigma Chemical Co., St. Louis, MO; in corn oil) i.m. (once daily) to induce pseudopregnancy (26). Animals were cannulated on day 40 (40.2 + 0.5 days; n = 4). All pseudopregnant gilts were given the Control treatment (sterile water i.m.) on day 42 (42.2 + 0.5 days; n = 4), followed by 15 mg PGF2o on day 45 (45.2 it 0.5 days; n = 4). Blood samples were collected before and after treatments, following a protocol identical to that described in Experiment 1. A second PGF2o injection (10 mg/gilt i.m.) was given following the 9 h blood sample to ensure complete luteolysis. Blood samoles: Blood samples were allowed to clot at room temperature and serum was collected after centrifugation at 2300 t-pm. Serum samples were stored at -20 C prior to assay for progesterone and porcine LH.

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Hormone radioimmunoa~ a) Progesterone: Progesterone assays of pig serum samples were performed by direct assay (without extraction) using Coat-a-count@ progesterone RIA kits (Diagnostic Products, Los Angeles, CA), using the human serum progesterone standards provided. In preliminary assays, a standard curve generated using progesterone supplemented charcoal-stripped pig serum was found to be superimposable with a standard curve obtained with human serum standards run in the same assay. Using pig serum pools containing approximately 24 @ml (high pool) and 4 rig/ml (low pool), inter-assay variation (5 assays) was found to be 6.5% and 1 l%, and intra-assay variation (10 replicates) was found to be 3.3% and 3.3%, respectively. Serum samples from the Control-treatment (day 42) and PGFzd-treatment (day 45) periods for each animal, and where possible, samples from each experiment, were assayed within the same assay. All samples were assayed in 5 assays. b) Luteinizing hormone: Serum samples collected during the immediate pre (-60 to 0) and post (+5 to +60)-treatment (Control and PGF2o) periods were assayed for LH concentrations using the double antibody RIA procedure described elsewhere (27). This procedure employed the anti-porcine LH serum GDN #566 (kindly supplied by Dr. G.D. Niswender, Colorado State Univ.) as the primary antibody, purified ovine LH LER #1056-C2 (kindly supplied by Dr. L.E. Reichert, Jr., Albany Medical College) as the radiolabelled (iodmated) ligand and unlabelled porcine LH LER #786-3 (supplied by Dr. Reichert) as reference standards. Using pig serum LH pools of 5 ng/ml (high) and 1 ng/ml (low), interassay variation was 5.1% and 8.2% (5 assays). Irma-assay variation was generally less than 5% for alI samples. statistics: Hormone data were analyzed using the least squares analysis of variance for repeated measures using the General Linear Models procedures of the Statistical Analysis System (28). In initial analyses, no significant differences (p > 0.05) were observed between pregnant females in Experiments 1 and 2, suggesting that differences in breed, use of estrus synchronization and the use of one versus two injections of PGF2o were not confounding influences. Therefore, these data from Experiments 1 and 2 were pooled for subsequent analyses. Two pregnant females failed to abort after PGF2o and were classified as a separate treatment in the statistical analyses. The statistical model for the pregnant animals included animal, treatment (control, PGF2, with abortion, or PGF2o without abortion), period (time before or after treatment), animal-within-treatment and two-way interactions. The main effect of treatment was tested using the animal-within-treatment mean square as the error term. When a significant treatment-by-period interaction was present (p < O.OS), modifications of this model were used to evaluate differences among periods within each treatment. When a significant effect of period was observed, differences between the pretreatment (-1 h) and all post-treatment (1 h to 57 h) periods were evaluated with pre-planned orthogonal contrasts. Hormone data from pseudopregnant gilts were analyzed in a similar manner as those from pregnant females except that in the statistical model, treatment groups were control and PGF2o.

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RESULTS: hetmant

frilts;

a) Serum progesterone: Figure la shows the changes in serum progesterone in response to control (on day 42) and PGF2o (day 45) treatments in a representative pregnant gilt (#29). In response to control treatment (day 42), serum progesterone concentrations fluctuated between 6 and 10 ng/ml and remained unchanged throughout the pre- and post-treatment (up to 9 h) periods (Fig. la). In contrast. whereas serum progesterone concentrations remained between 7 and 10 ng/ml in the period preceding PGF2o administration, progesterone concentrations increased briskly from 7.7 rig/ml (time 0) to 11.5 t&ml at 5 min. and continued to rise to reach maximal levels of -14 q/ml (- 75% above pre-treatment levels) between 10 and 45 min. after PGF2o injection. Thereafter, sentm progesterone concentrations returned to reach pre-treatment levels between 90 and 120 min. Subsequently, serum progesterone concentrations decreased further to -3 ng/mI between 225 and 540 min. Analyses of variance procedures revealed a significant treatment-by-period interaction for serum progesterone concentrations. Therefore, changes over periods (time; -1 h through 57 h) for control and PGFzo- treated gilts were evaluated, and are presented in Figure 2. For animals subjected to control treatment (on day 42; Fig. 2a), serum progesterone concentrations varied between 16 and 22 ng/ml throughout the posttreatment period and were not significantly different from the pm-treatment values (-19 @ml). In response to PGF2o treatment, a majority of the pregnant animals (7/9) aborted (at -27-4531) and the data from these animals were combined for presentation in Fig. 2b. w there was no difference in the rates of decline in serum progesterone concentrations at 21 - 57 h in pregnant animals which aborted, between animals receiving or not receiving, a second injection of PGF2o at 9 h). In these animals, serum progesterone concentrations were increased significantly (-22 ng/mI; p < 0.05) above pre-treatment levels (-1 h; -14 @ml) in the immediate post-treatment period (1 h), returned to approx. pre-treatment values at 2 h (-11 ng/ml, NS vs -1 h), and declined significantly between 3 and 9 h (-6-7 nglml, p < 0.05 vs -1 h). Subsequently, serum progesterone concentrations fell significantly (p < 0.05 vs -1 h) to -3 ngAnl at 21 h and continued to decline to reach 1 nglml or less at 45 and 57 h. The serum progesterone patterns of the remaining 2 (2/9) gilts which did not abort in response to PGF2o showed a similar pattern of change to those which did abort, including the increase at 1 h post(PGF& treatment, up to 21h. However, after this time, at 45 and 57 h, serum progesterone concentrations increased to attain pre-treatment values (data not shown).

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la 16

PGF2e - day 45

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I

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60

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160

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360

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460

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Figure 1: Acute changes in serum progesterone concentrations in a representative (a) pregnant (#29) and (b) pseudopregnant (#44) pig in response to control (day 42) and PGFza (day 45) injection.

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b) Serum LH: Figure 4a summarizes the mean serum LH concentrations for the immediate pm (-60 to 0 min.; -1 h) and post (+5 to +60 min.; 1 h)-treatment periods. In this Figure, data for all pregnant animals (n = 9) receiving PGF2, was combined since all animals displayed an acute increase in serum progesterone concentrations lh post treatment, whether or not abortion was induced. As shown, serum LH concentrations did not differ significantly between pre and post-treatment periods for either control or PGFb treatments. Pseudo-

. .

a) Serum progesterone: Figure lb shows the changes in serum progesterone concentrations in a representative pseudopregnant gilt (#44) in response to control (day 42) and PGF2o (day 45) - treatments. During the pre and post-treatment periods (control treatment), serum progesterone concentrations did not change markedly and varied between 5 and 11 ng/ml. However, in response to PGFzo-treatment, serum progesterone concentrations increased from 10 @ml at time 0 up to a maximum of -18 ng/ml by lo-15 min. following injection. Serum progesterone concentrations returned to pm-treatment values between 75 and 105 min. and subsequently declined to reach a low value of -2 ng/rnl by 360 mm. Analyses of variance procedures revealed a significant treatment-by-period interaction for serum progesterone concentrations in pseudopregnant gilts and therefore, changes over periods (tune; - 1 h through 57 h) for control and PGFa-treated gilts were evaluated and are presented in Figure 3. During the control-treatment period (Fig. 3a), serum progesterone concentrations remained between 7 and 12 ng/ml and there was no significant difference between pre- and post-treatment periods. In response to PGFzotreatment (Fig. 3b) however, serum progesterone concentrations were significantly increased at 1 h post-treatment (-14 ng/ml) compared with pre-treatment (-1 h; -9 ng/rnk p < 0.05). After returning to pre-treatment levels at 2 h (- 8 ng/ml; NS vs -1 h), serum progesterone concentrations continued to decline (p < 0.05,3 h to 57 h vs -1 h) to reach 1 ng/ml or less between 21 and 57 h. b) Serum LH: As shown in Fig. 4b, serum LH concentrations did not differ significantly between pre and post -treatment periods for either control or PGF2o treatments.

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Houra. pn and poti injection

tbun. pn and peat injection

Figures 2 and 3: Mean serum progesterone concentrations in pregnant (Fig. 2) and pseudopregnant (Fig. 3) gilts in response to (a) control treatment on day 42 (preg. n = 6, S.E.M. = 3.3 @ml; pseudopreg. n = 4, S.E.M. = 1.4 @ml), and (b) PGFzotreatment on day 45 @reg. n = 7. S.E.M. = 2.2 ngJml; pseudopreg. n = 4, S.E.M. = 0.7 t&ml). * p < 0.05 vs. -1 h @e-treatment). DISCUSSION: The data described in this paper show clearly that the administration of a luteolytic dose of PGF2, to both pregnant and pseudopregnant gilts in vivo, causes an acute increase in serum progesterone concentrations lasting approximately 1h. Subsequently however, serum progesterone concentrations declined (significantly by 34 h) to reach 1 ngIml or less between 21 and 57 h, a pattern more characteristic of a luteolytic response to PGFzo-treatment (6-16). Similar transient elevations in serum progesterone concentrations, preceding luteolysis, have been observed in response to

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PGF2o administration to non-pregnant (7, 23. 24) and pregnant gilts (6) in vivo. In view of the evidence indicating that PGF2o has dose-dependent stimulatoty effects on progesterone production by porcine luteal cells during short term incubations (4-6 h) in vitro (17; Earnest and Gadsby, unpublished), it is conceivable that the acute transient increase in serum progesterone concentrations observed in this study results from a direct stimulatory effect of PGFza on luteal steroidogenesis. Support for this conclusion comes from the studies of Watson and Maule-Walker (29) who showed, using superfused (in vitro) porcine luteal tissue slices, that a transient stimulation in progesterone output preceded the inhibitory (“luteolytic”) effects of PGF2o on progesterone production by this tissue. In our studies we could find no evidence of an increase in serum LH concentrations in association with the transient increase in serum progesterone concentrations following PGF2o-treatment, suggesting that the stimulatory effects of PGF2o on the corpora lutea of pregnancy and pseudopregnancy, were not mediated via elevated pituitary LH secretion. This observation was of particular interest since the corpora lutea of the extended luteal phases of pregnant and pseudopregnant pigs are dependent on pituitary LH-secretion (25). Similarly, serum LH concentrations were m found to be increased in association with increased serum progesterone concentrations in response to PGF2o when given to non-pregnant cycling gilts (23,24). Concerning a possible mechanism for the stimulatory effects of PGF2o on luteal progesterone secretion, it has been shown that an early response of luteal cells to PGF2o in vifro involves an immediate increase (within minutes) in intracellular calcium concentrations (30-32). This increase in intracellular calcium levels in luteal cells provoked by PGF2o is probably mediated by a stimulation of phospholipase C. increased phospholipid turnover and elevated intracellular inositol triphosphate concentrations (30, 33). as has been demonstrated for other hormones/growth factors (34,35). In recent studies, it has been shown that short term (4h) incubations of porcine (Ford, personal communication; Earnest and Gadsby, unpublished) and ovine (36) luteal cells with the calcium ionophore A23187, also results in increased progesterone production. Thus, it is possible that the acute stimulatory action of PGF2o on porcine luteal cell steroidogenesis may be mediated by a rapid elevation in intracellular calcium concentrations. In the present study, the acute transient increase in serum progesterone concentrations preceded complete luteolysis in a majority (7/9) of the pregnant animals and all pseudopregnant animals, suggesting that there may be a causal relationship between the early stimulatory, and later inhibitory (luteolytic), actions of PGF2o on porcine luteal cells. Even in the two pregnant animals which did not abort, the acute stimulatory phase was followed by a period of decreased luteal function reminiscent of luteolysis, although normal luteal function recovered subsequently. In other studies (23, 24), acute transient increases in serum progesterone accompanied the action of PGF2o given early in the estrous cycle, when it has been shown that PGF2o administration results in incomplete luteolysis, followed by full luteal recovery (9), similar to that shown in the two pregnant animals described above. Thus, although from our studies it is not possible to determine a physiological role for the acute stimulatory actions of PGF2o on the pig corpus luteum, it is tempting to speculate that the early effects of PGF2o on luteal cells (i.e. increased phospholipid turnover and increased intracellular calcium), of which the transient increase in steroidogenesis may be m manifestation, may be important in initiating intracellular events which lead ultimately to decreased progesterone production and diminished cellular function associated with luteolysis (37).

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4a 0

Control - day 42

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Figure 4: Mean serum LH concentrations in (a) pregnant (n = 9) and (b) pseudopregnant (n = 4) gilts in response to control (day 42) and PGFza (day 45) treatments. Standard errors of means: +. 0.09 ng/ml (pregnant) and + 0.06 ng/ml (pseudopregnant). No significant differences were observed between pre (-lh) and post (lh) treatments (control and PGF2a) in pregnant or pseudopregnant gilts.

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In conclusion, we have shown that the administration of PGF2o to pregnant and pseudopregnant gilts causes an acute, transient (-1 h) increase in serum progesterone concentrations, which preceded the subsequent decline in serum progesterone concentrations associated with luteolysis. This acute response to PGF2o was not associated with an increase in serum LH concentrations. In view of the stimulatory potential of PGF2o on porcine luteal cell progesterone production in vitro. one explanation for the acute increase in serum progesterone, is a rapid and direct stimulatory action of PGF2o on luteal steroidogenesis in vivo . Future studies will be directed towards determining the physiological role of the acute stimulatory effects on luteal cell progesterone production, in relation to the overall luteolytic action of PGF2, in the pig. ACKNOWLEDGEMENTS: We thank the Department of Animal Science for supplying some of the pigs used in this study, and for the use of the Unit I Swine Facility, where these studies were conducted. In addition, we thank Dr. G.D. Niswender (Dept. of Physiology and Biophysics, Colorado State University) for supplying the anti-porcine LH serum and Dr. L.E. Reichert, Jr. (Dept. of Biochemistry, Albany Medical College) for supplying porcine LH, used for the LH radioimmunoassay. We also thank Joan Metcalf for assisting with estrus detection, animal care/feeding, Greg Richards, Jack Bradley and Brian Ameson for their assistance with estrous detection, hormone injection and blood sampling, and Mary Lancaster for performing serum progesterone assays, data analysis and figure preparation. We gratefully acknowledge Dr. Billy Flowers for his invaluable advice/assistance with statistical analysis of data, and we thank Drs. Jack Britt and Billy Flowers for their helpful criticisms/comments during the preparation of this manuscript. REFERENCES: 1. Gleeson, A.R., G.D. Thobum and R.I. Cox. Prostaglandin F concentrations in the utero-ovarian venous plasma of the sow during the late luteal phase of the oestrous cycle. Prostaglandins 5521. 1974. 2. Moeljono, M.P.E., W.W. Thatcher, F.W. Bazer. M. Frank, L.J. Owens and C.J. Wilcox. A study of prostaglandii F2o as the luteolysin in swine: Il Characterization and comparison of prostaglandin F, estrogens and progestin concentrations in utero-ovarian vein plasma of nonpregnant and pregnant gilts. Prostaglandins 14543. 1977. 3. Nara, B.S. and N.L. First. Effects of indomethacin parturition in swine. J. Anim. Sci. 52:1360. 1981.

and prostaglandin

F2o on

4. Kraeling, R.R., G.B. Rampacek and T.E. Kiser. Corpus luteum function after indomethacin treatment during the estrous cycle and following hyesterectomy in the gilt. Biol. Reprod. 25:511. 1981. 5. Akinlosotu, B.A., J.R. Diehl and T. Gimenez. Prostaglandin E2 counteracts the effects of PGF2o in indomethacin treated cycling gilts. Prostaglandins 35:81. 1988. 6. Diehl, J.R. and B.N. Day. Effect of prostaglandin F2o on luteal function in swine. J. Anim. Sci. 39:392. 1974.

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7. Gleeson, A.R. Luteal function in the cyclic sow after infusion of prostaglandin through a uterine vein. J. Reprod. Fertil. 36:487. 1974.

F2o

8. Hallford, D.M., R.P. Wettemann, E.J. Turman and LT. Omtvedt. Luteal function in gilts after prostaglandin F2o. J. Anim. Sci. 41:1706. 1975. 9. Connor, L., G.D. Phillips and W.M. Palmer. Effects of prostaglandin F2o on the estrous cycle and hormone levels in gilts. Can. J. Anim. Sci. 56:661. 1976. 10. Guthrie, H.D. and C. Polge. Luteal function and oestrus in gilts treated with a synthetic analogue of prostaglandin F2o (ICI 79,939) at various times during the oestrous cycle. J. Reprod. Fertil. 48:423. 1976. 11. Kzymowski, T., J. Kotwica, S. Okrasa, T. Doboszynska and A. Ziecik. Luteal function in sows after unilateral unfusion of PGF2d into the anterior uterine vein on different days on the oestrous cycle. J. Reprod. Fertil. 54:21. 1978. 12. Wettemann, R.P., D.M. Hallford, D.L. Kreider and E.J. Tut-man. Influence of prostaglandin F2o on endocrine changes at parturition in gilts. J. Anim. Sci. 44:106. 1977. 13. Pressing, A.L., G.D. Dial, C.M. Stroud. G.W. Almond and O.W. Robison. Prostaglandin-induced abortion in swine: Endocrine changes and influence on subsequent reproductive activity. Am. J. Vet. Res. 48:45. 1987. 14. Moeljono. M.P.E., F.W. Bazer and W.W. Thatcher. A study of prostaglandin F2o as the luteolysin in swine: I. Effects of prostaglandin F2o in hysterectomized gilts. Prostaglandins 11:737. 1976. 15. Kraeling, R.R., C.R. Barb and B.J. Davis. Prostaglandin-induced regression of porcine corpora lutea maintained by estrogen. Prostaglandins 9:459.1975. 16. Guthrie, H.D. Estrous synchronization and fertility in gilts treated with estradiolbenzoate and prostaglandin F2e. Theriogenology 4:69. 1975. 17. Mattioli, M., G. Galeati, A. Prandi and E. Seren. Effect of PGF2, on progesterone production in swine luteal cells at different stages of the luteal phase. Prostaglandins, Leukotrienes and Medicine 17:43.1985. 18. Thomas, J.P., L.J. Dorflinger and H.R. Behrman. Mechanism of the rapid antigonadotropic action of prostaglandins in cultured luteal cells. Proc. Natl. Acad. Sci. USA. 75:1344. 1978. 19. Weston, P.G. and J.E. Hixon. Effects of prostaglandin F2e administration on in vitro progesterone synthesis by bovine corpora lutea. Biol. Reprod. 22:259. 1980. 20. Alila, H.W., R.A. Corradino and W. Hansel. A comparison of the effects of cyclooxygenase prostanoids on progesterone production by small and large bovine luteal cells. Prostaglandins 36:259. 1988.

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432

H. Dehrman

Received:

lo-l-90

Accepted:

l-30-91

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