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 pre-
and 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.

MAY 1991 VOL. 41 NO. 5 419

PROSTAGLANDINS

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 well-
established luteolytic (i.e. decreased serum progesterone concentrations) actions of
PGFzo, which are detectable by 4 - 12 h following PGF2o administration to the non-
pregnant 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.

420 MAY 1991 VOL. 41 NO. 5

 PROSTAGLANDINS

’ .
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 jugular-
vein cannula. The cannulae were used to collect twice daily blood samples on days 40-
42, 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.

MAY 1991 VOL. 41 NO. 5 421

PROSTAGLANDINS

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.

422 MAY 1991 VOL. 41 NO. 5

 PROSTAGLANDINS

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 post-
treatment 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).

MAY 1991 VOL. 41 NO. 5 423

PROSTAGLANDINS

la
16

PGF2e - day 45

___(3___4___“““---’ I
6

4
I

0
-60 0 60 120 160 240 300 360 420 460 5 0
Minutes - pre and post injection

lb
20
I
18 ___e_. Control - day 42
16 _ PGF2a - day 45

14

12 I
.d
.’
10 .’

o-..,....-
-60 0 60 120 180 240 300 360 420 480 6 0

Minutes - pre and post injection

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.

424 MAY 1991 VOL. 41 NO. 5

 PROSTAGLANDINS

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 PGFzo-
treatment (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.

MAY 1991 VOL. 41 NO. 5 425

PROSTAGLANDINS

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) PGFzo-
treatment 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 3-
4 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

426 MAY 1991 VOL. 41 NO. 5

 PROSTAGLANDINS

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).

MAY 1991 VOL. 41 NO. 5 427

 PROSTAGLANDINS

4a

0 Control - day 42

0.6 -

0.6 -

0.4 -

0.2 -

0.0 +
-1 1

Time - pre and post injection (h)

4b
0.4 -

0 COnWol -day 42

n WF2a -day 46
0.3 -

0.2 -

0.1 -

0.0 . 7
-1 1

Time - pre and post injection (h)

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.

428 MAY 1991 VOL. 41 NO. 5

 PROSTAGLANDINS

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 and prostaglandin F2o on
parturition in swine. J. Anim. Sci. 52:1360. 1981.

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.

MAY 1991 VOL. 41 NO. 5 429

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7. Gleeson, A.R. Luteal function in the cyclic sow after infusion of prostaglandin F2o
through a uterine vein. J. Reprod. Fertil. 36:487. 1974.

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 estradiol-
benzoate 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.

430 MAY 1991 VOL. 41 NO. 5

 PROSTAGLANDINS

21. Richardson, M.C. and G.M. Masson. Progesterone production by dispersed cells
from human corpus luteum: stimulation by gonadotrophins and prostaglandin F2o; lack
of response to adrenalin and isoprenaline. J. Endocr. 87:247. 1980.

22. Stouffer, R.L., W.E. Nixon and G.D. Hodgen. Disparate effects of prostaglandins
on basal and gonadotropin-stimulated progesterone production by luteal cells isolated
from rhesus monkeys during the menstrual cycle and pregnancy. Biol. Reprod. 20:897.
1979.

23. Lindloff, G., W. Holtz, F. Elsaesser, K. Kreikenbaum and D. Smidt. The effect of
prostaglandin F2o on corpus luteum function in the Gottingen minature pig. Biol.
Reprod. 15:303. 1976.

24. Berghom, K.A., L.A. Edgerton, G.L. Cromwell and T.S. Stahly. Serum
progesterone and luteinizing hormone following prostaglandin F2o during the sow’s
estrous cycle. Anim. Reprod. Sci. 19:273. 1989.

25. Anderson, L.L. and R.M. Melampy. Hypophysial and uterine influences on pig
luteal function. In: Reproduction in the Female Mammal. (G.E. Lamming and E.C.
Amoroso, eds.). Butterworths, London, p. 285. 1967

26. Frank, M., F.W. Bazer, W.W. Thatcher and C.J. Wilcox. A study of prostaglandin
F2o as the luteolysin in swine: III. Effects of estradiol valerate on prostaglandin F,
progestins, estrone and estradiol concentrations in the utero-ovarian vein of non-
pregnant gilts. Prostaglandins 14: 1183. 1977

27. Almond, G.W. and G.D. Dial. Estradiol feedback inhibition of luteinizing hormone
concentrations in the anestrous sow. J. Anim. Sci. 68:1077. 1990.

28. Spector, P.C., J.H. Goodnight, J.P. Sal1 and W.S. Sarle. The GLM procedure. In:
SAS User’s guide: Statistics. (S.P. Joyner, J.P. Sal1 and A.T. Allen, eds.). SAS
Instutute Inc., Cary, N.C.,1985, p. 433.

29. Watson, J. and F.M. Maule-Walker. Effects of prostaglandin F2o and uterine
extracts on progesterone secretion in vitro by superfused pig corpora lutea. J. Reprod.
Fertil. 51:393. 1977.

30. Davis, J.S., L.L. Weakland, D.A. Weiland, R.V. Farese and L.A. West.
Prostaglandin F2o stimulates phosphatidylinositol 4,5-bisphosphate hydrolysis and
mobilizes intracellular Caz+ in bovine luteal cells. Proc. Natl. Acad. Sci. USA 84:3728.
1987.

31. Pepperell, J.R., S.L. Preston and H.R. Berhman, The antigonadotropic action of
prostaglandin F2o is not mediated by elevated cytosolic calcium levels in rat luteal cells,
Endocrinology 125:144.1989.

32. Wiltbank, M.C., P.B. Guthrie, M.P. Mattson, S.B. Kater and G.D. Niswender.
Hormonal regulation of free intracellular calcium concentrations in small and large ovine
luteal cells. Biol. Reprod. 41:771. 1989.

MAY 1991 VOL. 41 NO. 5 431

PROSTAGLANDINS

33. Leung, P.C.K., T. Minegishi, F. Ma, F. Zhou and B. Ho-Yuen. Induction of

polyphosphoinositide breakdown in rat corpus luteum by prostaglandin F2o.
Endocrinology 119:12. 1986.

34. Nishizuka, Y. Studies and perspectives of protein kinase C. Science 233:30X 1986.

35. Rasmussen, H. and P.Q. Barrett. Calcium messenger system: An integrated view.
Physiological Reviews 64:938. 1984.

36. Conley, AI. and S.P. Ford. Effects of TPA, A23187, and prostaglandin F2o on
progesterone synthesis by dispersed ovine luteal cells. Biol. Reprod. 40:1224. 1989.

37. Niswender, G.D. and T.M. Nett. The corpus luteum and its control. In: The
Physiology of Reproduction, Vol. 1 (E. Knobil and J.D. Neill, eds). Raven Press, New
York, 1988, p. 489.

Editor: H. Dehrman Received: lo-l-90 Accepted: l-30-91

432 MAY 1991 VOL. 41 NO. 5