ON PREGNANCY IN HAMSTERS: ACTION OF PROSTAGLANDIN F LUTEOLYTIC AND E%i%A-OVARIAN EFFECTS
R. A. Edgren, D. L. Gawlak and Sheila Stewart Endocrine Research Warner-Lambert Co., Morris Plains, New Jersey
ABSTRACT Pregnancies in hamsters may be terminated with 10 ug PGF2, administered b.i.d. on days 4, 5 and 6 of gestation. Small (250 ug and above) daily injections of progesterone on the same days will reverse this PG effect: in contradistinction, 10 mq of-progesterone per day failed to maintain normal pregnancies in hamsters spayed on day 5. Daily administration of 3 mg of progesterone and 1 vg of estrone essentially normalized the gestation; administration of PGF at 10 mg on days 5, 6 and 7 of pregnancy in steroid-maintain.& 8 rats, resulted in pregnancy termination in all animals, while 1 mg was partly effective. These data demonstrate an extra-ovarian site of action of prostaglandin FZcl on pregnancy in hamsters.
PROSTAGLANDINS MAY
1975
VOL.
9 NO. 5
829
PROSTAGLANDINS
INTRODUCTION Gutknecht, Wyngarden and Pharriss (1) first showed that progesterone would reverse the effects of PGF on pregnant hamsters, and this observation was confirmed by Labh&twar (2). We (3) have recently quantified the effects of PGF on gravid hamsters and found the prostaglandin to be active at280ses far lower than those employed by the Upjohn group (1) or Labhsetwar (2). Using these newer data as a base, we have now reexamined the "anti-PG" effects of progesterone, extended our studies to steroidal support of hamster pregnancy, and examined the effects of PGF2, in steroid-maintained, spayed, pregnant animals.
MATERIALS AND METHODS Adult female hamsters were obtained from the Lakeview Hamster Colony, Newfield, New Jersey on the day sperm were observed in the vaginal smear (defined as day 1 of pregnancy). Prostaglandins were administered as solutions of 25% (V/V) absolute alcohol/ water and NaHC03 (equivalent amounts) and diluted to dose with normal saline. In the studies with intact hamsters, PG's were administered subcutaneously, twice daily on days 4, 5 and 6 of pregnancy. Progesterone (with or without estrone) was administered subcutaneously once daily on the same days as the PG's in 0.1 ml of sesame oil. In other studies pregnant hamsters were spayed on day 5 of pregnancy and received daily, subcutaneous, injections of progesterone (with or without estrogen) in 0.1 ml of sesame oil until autopsy. In the experiment involving PGFZa in spayed, steroid-maintained hamsters, the PG was given b.i.d. on days 5, 6 and 7 of pregnancy, while the steroids were administered once daily from day 5 to 15. Autopsy was performed on day 15. At autopsy, weights of body and uterus plus contents were recorded along with numbers of implantation sites, if any. Each group of hamsters consisted of 6-10 animals.
RESULTS AND DISCUSSION Ten )-lg twice daily on days 4, 5 and 6 of pregnancy was since it was almost 100% selected as the basic dose of PGF effective in terminating pregnant3 'in hamsters (3). In contrast, Gutknecht, Wyngarden and Pharriss (-1)employed a closeof 100 us/
830
MAY 1975
VOL. 9 NO. 5
PROSTAGLANDINS
hamster/day and Labhsetwar (2) employed 50 ug/day; more recently Lau, Saksena and Chang (4) showed a single 100 ug silastic implant of PGF2, was 100% effective. The 10 pg dose was highly efficacous in this series of experiments, and none of the hamsters treated with this dose was pregnant at autopsy (Table I). By contrast Gutknecht, Cornette and Pharriss (5) showed that twice daily administration of 800 ug of PGF7.awas required in rats to produce complete suppression of pregnancy on day 4-6. Thus, on a per animal basis, approximately 80 times more PGF2, was needed for pregnancy termination in rats than in hamsters. This differential is even more striking when body weight is taken into consideration: our pregnant hamsters weighed only ri to 2/3 as much as the pregnant rats employed in our laboratory. The simultaneous administration of progesterone and the PG permitted hamster pregnancy to proceed to autopsy, just prior to term, in an apparently normal manner (Table I). Progesterone doses between 250 and 4000 ug/day were essentially completely effective in normalizing pregnancy, whereas 10 and 30 ug had daily dose of progesterone minimal "anti-PG" effects. The 100 I_rg restored approximately 50% of the pregnancies. This high degree of sensitivity of PG-treated hamsters to progesterone was not reflected in earlier work, which did not attempt quantification of the steroid. Gutknecht, Wyngarden and Pharriss (1) employed daily doses of 12 mg of progesterone, Labhsetwar (2) used 4 mg and Saksena, Lau and Chang (5) administered 1.5 mg b.i.d. (Table I), and Chatterjee administered 5 mg on days 10 to 12 of pregnancy (6). In our (3) earlier studies with PG's in hamsters the effects appeared to be an all-or-nothing situation, i.e., the PG-treated sperm-positive hamsters were either not pregnant at the time of sacrifice or had normal fetal complements and weights of the uterine-fetal-placental units. Only the proportion of animals pregnant was affected, whereas no sign of pregnancy was observed in other animals. Progesterone reversal of PG effects is similarly all-or-nothing. This experiment suggested a number of questions concerning the ovarian maintenance of pregnancy in hamsters, and prompted the following experiments. Progesterone, over the dose range of lOOO-10,000 ug daily, resulted in essentially 100% maintenance of pregnancy in spayed hamsters (Table II); 300 ug was the approximate EDso, and lower doses failed to have any pregnancy-maintaining effect. The fetal complement appeared to be about normal in all animals in which pregnancies were maintained, however, no dose of progesterone alone resulted in normal weights of thefetal/ placental/uterine unit. This deficiency was corrected by the administration simultaneously with progesterone of 1 ug of estrone, which in itself was ineffective.
MAY
1975 VOL. 9 NO. 5
831
PROSTAGLANbINS
These data are in some disagreement with Orsini (7), who could maintain pregnancies to term with only progesterone at daily doses of about 4 mg. However, Orsini's data suggest widely differing hormonal requirements of hamsters depending on the time of ovariectomy. On the other hand Klein (7) found that both estrogens and progestagens were required for maintenance of pregnancy. Our data suggest that normal pregnancy in spayed hamsters depends upon an interaction of progesterone and estrone, the estrogen potentiating the effect of the progestagen at the doses studied. In comparison with rats, the dose of progesterone alone required by hamsters is very large indeed. On a per animal basis, doses of 5-10 mg per day will carry rat pregnancies from spaying to term in essentially normal condition , whereas 10 mg per day to the smaller female hamster was inadequate. The addition of small amounts of estrone is generally considered to potentiate the effect in rats, also, but in our experience the effect is not so marked as it appears in the hamsters , where 1 vg of estrone will almost normalize the maintenance effect of 1 and 3 mg of progesterone. It is evident from these studies (Tables I and II) that prostaglandin treatment and spaying are not comparable phenomena. are easily reversed The pregnancy-terminating effects of PGF by low doses of progesterone , whereas es3gone was required with massive doses of progesterone to compensate for removed ovaries. Additional quantification of steroid requirements is certainly warranted in hamsters. The studies of Gutknecht, Wyngarden and Pharriss (1) indicate will depress circulating progesterone during pregnancy, that PGF but does*#ot interfere with the fluctuations of progesterone levels usually found. In their studies, on days 5 and 6 and day 11 of normal gestation, progesterone was relatively low, and PG treatment on days 5 and 6 depressed progesterone levels to values approximating zero. Termination of the pregnancies was consistent at this time. It is, perhaps, not surprising that relatively low doses of progesterone are effective in reversing the effects of the PG at this time of normal low titres. The massive doses needed following spaying and the requirement for added estrogen may reflect higher progesterone titres normally present at other times during pregnancy and the failure of the placenta to produce estrogens. A final experiment involved the administration of PGF to spayed (day 5) steroid-maintained hamsters. Three mg of p $8gesterone plus 1 pg of estrone were employed as maintenance doses and resulted in an essential normalization of the pregnancies (Table III). The administration of PGF2, on days 5, 6 and 7 at
832
MAY 1975
VOL. 9 NO. 5
PROSTAGLANDINS
doses of 10 and 100 pg b.i.d. had no measurable effect on the pregnancies, while no females were gravid after an injection of reduced the proportion of pregnant 10 mg. The 1 mg dose of PGF animals, but fetal complemeneawas essentially normal. Since these studies employed ovariectomized animals, they demonstrate an extra-ovarian site of action of PGF . The effects of the PG during normal pregnancy on days 4, 5 and2g, or single doses up to about day 7 (3) are most probably ovarian (21, and probably reflect the well-known "luteolytic" action of the PG. Although even here ambiguities exist. Chatterjee (6) has maintained pregnancies in PGF -treated rats with prolactin, suggesting action at hypothal&%ic or pituitary sites. The mode-of-action of PGF in the animals with pregnancies supported by exogenous ste$8ids is far from clear: however, the recent demonstration of a potent PG-induced vasoconstriction in the rat omentum uteri (9) may be applicable here - a similar vasoconstriction may occur in the hamster uteri and lead to vascular deficiency and resorption.
MAY 1975
VOL. 9 NO. 5
833
PROSTAGLANDINS
ACKNOWLEDGEMENTS We are indebted to Ono Pharmaceutical Co., Ltd of Osaka, Japan for supplies of the prostaglandins. We are also indebted to Miss Carol Willenbecher for assistance in autopsy of the animals.
REFERENCES 1.
Gutknecht, G.D., Wyngarden, L.J. and Pharriss, B.B.: The Effect of Prostaglandin Faa on Ovarian and Plasma ProgesSot. x. terone Levels in the Pregnant Hamster. Proc. -Biol. & Med., 136:1151, 1971.
2.
Labhsetwar, A.: Effects of Prostaglandin F on Some ReproJ 'Endocrinol., 53: ductive Processes of Hamsters and Rats, _. 201, 1972.
3.
Gawlak, D.L., Stewart, S. and Edgren, R.A.: The Termination of Pregnancy in Hamsters with Prostaglandins. Prostaglandins, in press, 1974.
4.
Lau, I.F., Saksena, S.K., and Chang, M.C.: Midterm Abortion ’ with Silastic-PVP Implant Containing Prostaglandin F Rabbits, Rats and Hamsters. Fert. Steril., 25:839, %7;:
5.
Gutknecht, G.D., Cornette, J.C. and Pharriss, B.B.: Antifertility Properties of Prostaglandin Faa. Biol. Reprod., 1:367, 1969.
6.
Chatterjee, A.: Possible Mode of Action of Prostaglandins; Before and After V-Differential Effects of Prostaglandin F the Establishment of Placental Physiology2'?nPregnant Rats. Prostaglandins, 3:189, 1973.
7.
Orsini, M.W.: Morphological Evidence on the Intrauterine Career of the Ovum. InEnders, ea., Delayed Implantation, Univ. Chicago Press, 155, 1963.
8.
Klein, M.: Relation Between the Uterus and the Ovaries in the London B, 125:348, 1938. Pregnant Hamster. Proc. Roy. s., [cited from Orsini m.
9.
Cseply , J. and Csapo, A.I.: The Effect of Prostaglandin F2a on the Small Arteries of the Omentum Uteri of the Rat. Prostaglandins, 1:255, 1972.
834
MAY
1975
VOL. 9 NO. 5
-
*
Of pregnant
i
animals
10 !Jg
10 !Jg
100 Vg
10 ?Jg
30 llg
250 pg
10 Pg
10 119
500 lJg
10 ug 10 10 10 10
1 1 1 1
only
10
1
19
2
1000 !.lg
10
1
10 ug
10
1
4000 pg
2000 !.lg
!Jg
26
3
18
N
0
10 !Jg
10
10 PC3
3
Control
L
of Groups
No.
I
N
17
Pregnant
0
1
6
9
8
19
10
10
0
i
I
I
t
f
0
I i
/
0
12
10.7kO.88
60 10
10.6+0.71
11.0+0.73
90
80
I
11.2k0.61
i
100
10.5k1.49
12.3kO.33
;
100
100
0
I
10.3kO.4
0
94.4
HAMSTERS
Avg. No. Implantation Sites*
PREGNANT
% Pregnant
IN PGF2a-TREATED
I-
-!-
OF PROGESTERONE
Treatment / ProgesPGFZc, j terone
EFFECTS
TABLE
I
0.8+0.03
39
35.5k2.36
34.6k1.47
33.8k2.4
32.8k4.3
33.6t1.94
40.3t1.09
0.75to.03
34.2kO.93
Uterine/ Fetal/ Placental Units (gm)
!
Pregnant
Maintained
%
*
**
Spayed on Day 5 of pregnancy Pregnant animals only
1000 ?Jg
100
I
50
300 lJg
;
10.25kO.75
Continued
. . . .
10.25k1.34
2.9756.56
0.62kO.13
0 0
100 ug
9.75k1.11
0.25kO.11
I
0
0.24tO.03
0.22kO.04
38.4k4.17
0
;
Placental Units (gm)
30 !Jg
0
0
11.6+1.03
HAMSTERS*
-I- Uterine/Fetal/
IN SPAYED
0
I
ESTRONE
Implantation Sites**
AND/OR
10 vg
Progesterone
0
I N
II
OF PROGESTERONE
Castrate Control
N
-
EFFECT
100
I
I
MAINTAINING
Intact Controls
EXPERIMENT
Treatment
PREGNANCY
TABLE
EI 2 ul
z
0
I 0
100
Maintained
%
**
Spayed on Day 5 of pregnancy Pregnant animals only
100
Progesterone 3000 Llg + Estrone 1 pg
*
100
0
Progesterone 1000 ug + Estrone 1 pg
Estrone 1 1-19
89
Pregnant
N
ESTRONE
10.6tO.84
7.5kl.12
0
7.121.18
10.0+1.11
0
10.8+1.32
Implantation Sites**
AND/OR
II Cont'd
OF PROGESTERONE
Progesterone 10,000 ug
N
f
EFFECT
100
II
t
I
I
T
MAINTAINING
Progesterone 3000 ug
Castrate Controls
Intact Controls
EXPERIMENT
Treatment
PREGNANCY
TABLE
HAMSTERS*
29.023.69
26.2k3.50
0.25+0.01
13.8k2.01
10.9?1.11
0.22*0.01
35.8k3.48
Uterine/Fetal/ Placental Units (gm)
IN SPAYED
cn
©
©
~D
Q0
co
i00
43
Progesterone 3000 ~g + Estrone 1 ~g + PGF2s i00 ~g
Progesterone 3000 ~g + Estrone 1 ~g + PGF2u 1000 ~g
*
11.7±0.33
10.1±0.34
10.4±0.78
10.7±0.99
0
11.5±0.22
Implantation Sites
I
1.06±0.13
17.0±6.51
34.6±1.96
36.4±3.8
38.2+5.1
0.17±0.02
36.7±1.05
Uterine/Fetal Placental Units (~m)
Steroids were given once daily, from day 5 to autopsy on day 15; PGF2e was given b.i.d. on days 5, 6 and 7.
Progesterone 3000 ~g + Estrone 1 ~g + PGF2s 10,000 9g
i00
0
lO0
Maintained
Progesterone 3000 ~g + Estrone 1 ~g + PGF2e i0 ~g
Pre@nant
i00
N
%
ON SPAYED (DAY 5) PREGNANT HAMSTERS WITH PROGESTERONE PLUS ESTRONE
Progesterone 3000 ~g + Estrone 1 9g
Castrate Controls
Intact Controls
Treatment*
N
EFFECTS OF PGF~ MAINTAIN~
TABLE III
©
R. A. Edgren, D. L. Gawlak and Sheila Stewart Endocrine Research Warner-Lambert Co., Morris Plains, New Jersey
ABSTRACT Pregnancies in hamsters may be terminated with 10 ug PGF2, administered b.i.d. on days 4, 5 and 6 of gestation. Small (250 ug and above) daily injections of progesterone on the same days will reverse this PG effect: in contradistinction, 10 mq of-progesterone per day failed to maintain normal pregnancies in hamsters spayed on day 5. Daily administration of 3 mg of progesterone and 1 vg of estrone essentially normalized the gestation; administration of PGF at 10 mg on days 5, 6 and 7 of pregnancy in steroid-maintain.& 8 rats, resulted in pregnancy termination in all animals, while 1 mg was partly effective. These data demonstrate an extra-ovarian site of action of prostaglandin FZcl on pregnancy in hamsters.
PROSTAGLANDINS MAY
1975
VOL.
9 NO. 5
829
PROSTAGLANDINS
INTRODUCTION Gutknecht, Wyngarden and Pharriss (1) first showed that progesterone would reverse the effects of PGF on pregnant hamsters, and this observation was confirmed by Labh&twar (2). We (3) have recently quantified the effects of PGF on gravid hamsters and found the prostaglandin to be active at280ses far lower than those employed by the Upjohn group (1) or Labhsetwar (2). Using these newer data as a base, we have now reexamined the "anti-PG" effects of progesterone, extended our studies to steroidal support of hamster pregnancy, and examined the effects of PGF2, in steroid-maintained, spayed, pregnant animals.
MATERIALS AND METHODS Adult female hamsters were obtained from the Lakeview Hamster Colony, Newfield, New Jersey on the day sperm were observed in the vaginal smear (defined as day 1 of pregnancy). Prostaglandins were administered as solutions of 25% (V/V) absolute alcohol/ water and NaHC03 (equivalent amounts) and diluted to dose with normal saline. In the studies with intact hamsters, PG's were administered subcutaneously, twice daily on days 4, 5 and 6 of pregnancy. Progesterone (with or without estrone) was administered subcutaneously once daily on the same days as the PG's in 0.1 ml of sesame oil. In other studies pregnant hamsters were spayed on day 5 of pregnancy and received daily, subcutaneous, injections of progesterone (with or without estrogen) in 0.1 ml of sesame oil until autopsy. In the experiment involving PGFZa in spayed, steroid-maintained hamsters, the PG was given b.i.d. on days 5, 6 and 7 of pregnancy, while the steroids were administered once daily from day 5 to 15. Autopsy was performed on day 15. At autopsy, weights of body and uterus plus contents were recorded along with numbers of implantation sites, if any. Each group of hamsters consisted of 6-10 animals.
RESULTS AND DISCUSSION Ten )-lg twice daily on days 4, 5 and 6 of pregnancy was since it was almost 100% selected as the basic dose of PGF effective in terminating pregnant3 'in hamsters (3). In contrast, Gutknecht, Wyngarden and Pharriss (-1)employed a closeof 100 us/
830
MAY 1975
VOL. 9 NO. 5
PROSTAGLANDINS
hamster/day and Labhsetwar (2) employed 50 ug/day; more recently Lau, Saksena and Chang (4) showed a single 100 ug silastic implant of PGF2, was 100% effective. The 10 pg dose was highly efficacous in this series of experiments, and none of the hamsters treated with this dose was pregnant at autopsy (Table I). By contrast Gutknecht, Cornette and Pharriss (5) showed that twice daily administration of 800 ug of PGF7.awas required in rats to produce complete suppression of pregnancy on day 4-6. Thus, on a per animal basis, approximately 80 times more PGF2, was needed for pregnancy termination in rats than in hamsters. This differential is even more striking when body weight is taken into consideration: our pregnant hamsters weighed only ri to 2/3 as much as the pregnant rats employed in our laboratory. The simultaneous administration of progesterone and the PG permitted hamster pregnancy to proceed to autopsy, just prior to term, in an apparently normal manner (Table I). Progesterone doses between 250 and 4000 ug/day were essentially completely effective in normalizing pregnancy, whereas 10 and 30 ug had daily dose of progesterone minimal "anti-PG" effects. The 100 I_rg restored approximately 50% of the pregnancies. This high degree of sensitivity of PG-treated hamsters to progesterone was not reflected in earlier work, which did not attempt quantification of the steroid. Gutknecht, Wyngarden and Pharriss (1) employed daily doses of 12 mg of progesterone, Labhsetwar (2) used 4 mg and Saksena, Lau and Chang (5) administered 1.5 mg b.i.d. (Table I), and Chatterjee administered 5 mg on days 10 to 12 of pregnancy (6). In our (3) earlier studies with PG's in hamsters the effects appeared to be an all-or-nothing situation, i.e., the PG-treated sperm-positive hamsters were either not pregnant at the time of sacrifice or had normal fetal complements and weights of the uterine-fetal-placental units. Only the proportion of animals pregnant was affected, whereas no sign of pregnancy was observed in other animals. Progesterone reversal of PG effects is similarly all-or-nothing. This experiment suggested a number of questions concerning the ovarian maintenance of pregnancy in hamsters, and prompted the following experiments. Progesterone, over the dose range of lOOO-10,000 ug daily, resulted in essentially 100% maintenance of pregnancy in spayed hamsters (Table II); 300 ug was the approximate EDso, and lower doses failed to have any pregnancy-maintaining effect. The fetal complement appeared to be about normal in all animals in which pregnancies were maintained, however, no dose of progesterone alone resulted in normal weights of thefetal/ placental/uterine unit. This deficiency was corrected by the administration simultaneously with progesterone of 1 ug of estrone, which in itself was ineffective.
MAY
1975 VOL. 9 NO. 5
831
PROSTAGLANbINS
These data are in some disagreement with Orsini (7), who could maintain pregnancies to term with only progesterone at daily doses of about 4 mg. However, Orsini's data suggest widely differing hormonal requirements of hamsters depending on the time of ovariectomy. On the other hand Klein (7) found that both estrogens and progestagens were required for maintenance of pregnancy. Our data suggest that normal pregnancy in spayed hamsters depends upon an interaction of progesterone and estrone, the estrogen potentiating the effect of the progestagen at the doses studied. In comparison with rats, the dose of progesterone alone required by hamsters is very large indeed. On a per animal basis, doses of 5-10 mg per day will carry rat pregnancies from spaying to term in essentially normal condition , whereas 10 mg per day to the smaller female hamster was inadequate. The addition of small amounts of estrone is generally considered to potentiate the effect in rats, also, but in our experience the effect is not so marked as it appears in the hamsters , where 1 vg of estrone will almost normalize the maintenance effect of 1 and 3 mg of progesterone. It is evident from these studies (Tables I and II) that prostaglandin treatment and spaying are not comparable phenomena. are easily reversed The pregnancy-terminating effects of PGF by low doses of progesterone , whereas es3gone was required with massive doses of progesterone to compensate for removed ovaries. Additional quantification of steroid requirements is certainly warranted in hamsters. The studies of Gutknecht, Wyngarden and Pharriss (1) indicate will depress circulating progesterone during pregnancy, that PGF but does*#ot interfere with the fluctuations of progesterone levels usually found. In their studies, on days 5 and 6 and day 11 of normal gestation, progesterone was relatively low, and PG treatment on days 5 and 6 depressed progesterone levels to values approximating zero. Termination of the pregnancies was consistent at this time. It is, perhaps, not surprising that relatively low doses of progesterone are effective in reversing the effects of the PG at this time of normal low titres. The massive doses needed following spaying and the requirement for added estrogen may reflect higher progesterone titres normally present at other times during pregnancy and the failure of the placenta to produce estrogens. A final experiment involved the administration of PGF to spayed (day 5) steroid-maintained hamsters. Three mg of p $8gesterone plus 1 pg of estrone were employed as maintenance doses and resulted in an essential normalization of the pregnancies (Table III). The administration of PGF2, on days 5, 6 and 7 at
832
MAY 1975
VOL. 9 NO. 5
PROSTAGLANDINS
doses of 10 and 100 pg b.i.d. had no measurable effect on the pregnancies, while no females were gravid after an injection of reduced the proportion of pregnant 10 mg. The 1 mg dose of PGF animals, but fetal complemeneawas essentially normal. Since these studies employed ovariectomized animals, they demonstrate an extra-ovarian site of action of PGF . The effects of the PG during normal pregnancy on days 4, 5 and2g, or single doses up to about day 7 (3) are most probably ovarian (21, and probably reflect the well-known "luteolytic" action of the PG. Although even here ambiguities exist. Chatterjee (6) has maintained pregnancies in PGF -treated rats with prolactin, suggesting action at hypothal&%ic or pituitary sites. The mode-of-action of PGF in the animals with pregnancies supported by exogenous ste$8ids is far from clear: however, the recent demonstration of a potent PG-induced vasoconstriction in the rat omentum uteri (9) may be applicable here - a similar vasoconstriction may occur in the hamster uteri and lead to vascular deficiency and resorption.
MAY 1975
VOL. 9 NO. 5
833
PROSTAGLANDINS
ACKNOWLEDGEMENTS We are indebted to Ono Pharmaceutical Co., Ltd of Osaka, Japan for supplies of the prostaglandins. We are also indebted to Miss Carol Willenbecher for assistance in autopsy of the animals.
REFERENCES 1.
Gutknecht, G.D., Wyngarden, L.J. and Pharriss, B.B.: The Effect of Prostaglandin Faa on Ovarian and Plasma ProgesSot. x. terone Levels in the Pregnant Hamster. Proc. -Biol. & Med., 136:1151, 1971.
2.
Labhsetwar, A.: Effects of Prostaglandin F on Some ReproJ 'Endocrinol., 53: ductive Processes of Hamsters and Rats, _. 201, 1972.
3.
Gawlak, D.L., Stewart, S. and Edgren, R.A.: The Termination of Pregnancy in Hamsters with Prostaglandins. Prostaglandins, in press, 1974.
4.
Lau, I.F., Saksena, S.K., and Chang, M.C.: Midterm Abortion ’ with Silastic-PVP Implant Containing Prostaglandin F Rabbits, Rats and Hamsters. Fert. Steril., 25:839, %7;:
5.
Gutknecht, G.D., Cornette, J.C. and Pharriss, B.B.: Antifertility Properties of Prostaglandin Faa. Biol. Reprod., 1:367, 1969.
6.
Chatterjee, A.: Possible Mode of Action of Prostaglandins; Before and After V-Differential Effects of Prostaglandin F the Establishment of Placental Physiology2'?nPregnant Rats. Prostaglandins, 3:189, 1973.
7.
Orsini, M.W.: Morphological Evidence on the Intrauterine Career of the Ovum. InEnders, ea., Delayed Implantation, Univ. Chicago Press, 155, 1963.
8.
Klein, M.: Relation Between the Uterus and the Ovaries in the London B, 125:348, 1938. Pregnant Hamster. Proc. Roy. s., [cited from Orsini m.
9.
Cseply , J. and Csapo, A.I.: The Effect of Prostaglandin F2a on the Small Arteries of the Omentum Uteri of the Rat. Prostaglandins, 1:255, 1972.
834
MAY
1975
VOL. 9 NO. 5
-
*
Of pregnant
i
animals
10 !Jg
10 !Jg
100 Vg
10 ?Jg
30 llg
250 pg
10 Pg
10 119
500 lJg
10 ug 10 10 10 10
1 1 1 1
only
10
1
19
2
1000 !.lg
10
1
10 ug
10
1
4000 pg
2000 !.lg
!Jg
26
3
18
N
0
10 !Jg
10
10 PC3
3
Control
L
of Groups
No.
I
N
17
Pregnant
0
1
6
9
8
19
10
10
0
i
I
I
t
f
0
I i
/
0
12
10.7kO.88
60 10
10.6+0.71
11.0+0.73
90
80
I
11.2k0.61
i
100
10.5k1.49
12.3kO.33
;
100
100
0
I
10.3kO.4
0
94.4
HAMSTERS
Avg. No. Implantation Sites*
PREGNANT
% Pregnant
IN PGF2a-TREATED
I-
-!-
OF PROGESTERONE
Treatment / ProgesPGFZc, j terone
EFFECTS
TABLE
I
0.8+0.03
39
35.5k2.36
34.6k1.47
33.8k2.4
32.8k4.3
33.6t1.94
40.3t1.09
0.75to.03
34.2kO.93
Uterine/ Fetal/ Placental Units (gm)
!
Pregnant
Maintained
%
*
**
Spayed on Day 5 of pregnancy Pregnant animals only
1000 ?Jg
100
I
50
300 lJg
;
10.25kO.75
Continued
. . . .
10.25k1.34
2.9756.56
0.62kO.13
0 0
100 ug
9.75k1.11
0.25kO.11
I
0
0.24tO.03
0.22kO.04
38.4k4.17
0
;
Placental Units (gm)
30 !Jg
0
0
11.6+1.03
HAMSTERS*
-I- Uterine/Fetal/
IN SPAYED
0
I
ESTRONE
Implantation Sites**
AND/OR
10 vg
Progesterone
0
I N
II
OF PROGESTERONE
Castrate Control
N
-
EFFECT
100
I
I
MAINTAINING
Intact Controls
EXPERIMENT
Treatment
PREGNANCY
TABLE
EI 2 ul
z
0
I 0
100
Maintained
%
**
Spayed on Day 5 of pregnancy Pregnant animals only
100
Progesterone 3000 Llg + Estrone 1 pg
*
100
0
Progesterone 1000 ug + Estrone 1 pg
Estrone 1 1-19
89
Pregnant
N
ESTRONE
10.6tO.84
7.5kl.12
0
7.121.18
10.0+1.11
0
10.8+1.32
Implantation Sites**
AND/OR
II Cont'd
OF PROGESTERONE
Progesterone 10,000 ug
N
f
EFFECT
100
II
t
I
I
T
MAINTAINING
Progesterone 3000 ug
Castrate Controls
Intact Controls
EXPERIMENT
Treatment
PREGNANCY
TABLE
HAMSTERS*
29.023.69
26.2k3.50
0.25+0.01
13.8k2.01
10.9?1.11
0.22*0.01
35.8k3.48
Uterine/Fetal/ Placental Units (gm)
IN SPAYED
cn
©
©
~D
Q0
co
i00
43
Progesterone 3000 ~g + Estrone 1 ~g + PGF2s i00 ~g
Progesterone 3000 ~g + Estrone 1 ~g + PGF2u 1000 ~g
*
11.7±0.33
10.1±0.34
10.4±0.78
10.7±0.99
0
11.5±0.22
Implantation Sites
I
1.06±0.13
17.0±6.51
34.6±1.96
36.4±3.8
38.2+5.1
0.17±0.02
36.7±1.05
Uterine/Fetal Placental Units (~m)
Steroids were given once daily, from day 5 to autopsy on day 15; PGF2e was given b.i.d. on days 5, 6 and 7.
Progesterone 3000 ~g + Estrone 1 ~g + PGF2s 10,000 9g
i00
0
lO0
Maintained
Progesterone 3000 ~g + Estrone 1 ~g + PGF2e i0 ~g
Pre@nant
i00
N
%
ON SPAYED (DAY 5) PREGNANT HAMSTERS WITH PROGESTERONE PLUS ESTRONE
Progesterone 3000 ~g + Estrone 1 9g
Castrate Controls
Intact Controls
Treatment*
N
EFFECTS OF PGF~ MAINTAIN~
TABLE III
©
