INHIBITORY EFFECT OF PROGESTERONE ON THE LACTOGENIC AND ABORTIVE ACTION OF PROSTAGLANDIN F2α

1975 ◽  
Vol 66 (1) ◽  
pp. 21-29 ◽  
Author(s):  
NELIA T. VERMOUTH ◽  
R. P. DEIS

SUMMARY The effect of ovariectomy, progesterone and prolactin treatment on the action of prostaglandin F2α (PGF2α) was determined in pregnant rats. PGF2α (150 μg × 2) injected i.p. on day 19 or 18 of pregnancy induced lactogenesis about 25 h later and abortion on days 20 and 21 of pregnancy. Treatment with PGF2α (100 μg × 2 or 50 μg × 2) on day 19 induced lactogenesis around 22 or 38 h later, respectively, and abortion on day 21. PGF2α treatment on day 17 was less effective. Unilateral ovariectomy on day 17 of pregnancy induced lactogenesis 32 h later but not abortion. PGF2α (150 μg × 2) given on the day of surgery advanced lactogenesis 12 h and rats aborted on day 19. Bilateral ovariectomy on day 17 induced abortion between days 20 to 21, but if a single dose of PGF2α (300 μg) was injected on day 18, all the ovariectomized rats aborted on day 19. Progesterone (10 mg) injected into rats treated with PGF2α (150 μg × 2) on day 18, prevented abortion and delayed lactogenesis. Prolactin (1 mg × 4) treatment delayed only abortion. Serum prolactin levels were significantly higher 12 h after the last dose of PGF2α (150 μg × 2) in rats treated on days 17, 18 or 19 of pregnancy. Pretreatment with progesterone prevented the rise in prolactin concentration. These results suggest that the lactogenic and abortive action of PGF2α may be dependent on the uterine and plasma concentration of progesterone.

1981 ◽  
Vol 89 (3) ◽  
pp. 399-404 ◽  
Author(s):  
D. G. PORTER ◽  
SANDRA J. DOWNING ◽  
JANE M. C. BRADSHAW

Relaxin in doses of 5 μg i.v. completely but reversibly abolishes 'spontaneous' myometrial activity in anaesthetized ovariectomized rats. Similar levels of myometrial activity, evoked in oestrogen-treated rats (which normally have quiescent uteri) by infusions of oxytocin or prostaglandin F2α (PGF2α), were also reduced to complete quiescence by relaxin in small doses. However when spontaneous myometrial activity in untreated ovariectomized rats was slightly stimulated by oxytocin the uterus became completely refractory to the inhibitory effects of relaxin even at doses of 50 μg. Relaxin was also ineffective in reducing myometrial activity in similar rats during intra-arterial infusion of PGF2α. It is suggested that the ability of relaxin to inhibit uterine smooth muscle during exogenous stimulation is oestrogen-dependent.


1972 ◽  
Vol 53 (3) ◽  
pp. 355-NP ◽  
Author(s):  
K. BROWN-GRANT ◽  
A. W. ROGERS

SUMMARY Previous studies have shown that under the influence of progesterone the concentrations of radioiodide in the uterus and oviduct of the rat are maintained at levels higher than that in the plasma. In the present experiments the uterus and oviducts from rats killed 2 h after the injection of Na125I were autoradiographed by a technique which permits the localization of diffusible radioactive material. In intact non-pregnant rats and ovariectomized rats not injected with progesterone, uniformly low grain densities were observed over sections of oviduct and uterus with the exception of the epithelium and lumen of the oviduct where some increase in grain density was observed. In intact and ovariectomized rats treated with progesterone and in rats killed on Day 3 or 4 of pregnancy, grain densities over the epithelium and lumen of the oviduct were very high but the fimbria of the oviduct were consistently unlabelled. The stroma underlying the oviduct epithelium was also labelled. In the uteri of these animals the principal site of concentration of radioiodide was the luminal epithelium, but for technical reasons it was not possible to exclude the stroma immediately adjacent to the luminal epithelium as a less active site of concentration of iodide. No other site in the uterus concentrated radioiodide. The luminal epithelium occupies less than 3% of the volume of the uterus in ovariectomized rats: if this tissue is taken as the sole site of iodide concentration in the uterus, the levels reached in these cells must be at least a hundred times that of the plasma when the overall uterus: plasma concentration ratio for radioiodide is 4 or more.


1975 ◽  
Vol 66 (3) ◽  
pp. 329-338 ◽  
Author(s):  
N. B. HAYNES ◽  
H. D. HAFS ◽  
R. J. WATERS ◽  
J. G. MANNS ◽  
A. RILEY

SUMMARY The concentrations of peripheral plasma testosterone were measured by radioimmunoassay in samples collected from five bulls, each given i.m. injections of 0, 5, 15, 30 and 60 mg prostaglandin F2α (PGF2α). Synchronized peaks in testosterone concentration occurred with maximum values 1–2 h after treatment. These increases of testosterone persisted significantly longer than those observed to occur as natural episodic peaks during two 24 h periods in the same bulls. The mean peak testosterone concentration after PGF2α injection was related to the dose of PGF2α, values after 60 and 30 mg doses being significantly greater than after 15 mg. The response produced by a 5 mg dose was not significant. The results indicate that intramuscular injection of PGF2α acutely stimulates synthesis and release of testosterone in bulls.


1976 ◽  
Vol 69 (3) ◽  
pp. 395-399 ◽  
Author(s):  
J. PRILUSKY ◽  
R. P. DEIS

SUMMARY The effect of prostaglandin F2α (PGF2α) on milk ejection and on oxytocin release during suckling for one or two periods of 30 min was studied in lactating rats. Doses of PGF2α (20 or 40 μg) were injected i.p. 15 min before the suckling period. Control rats were injected with physiological saline. An inhibition of milk ejection proportional to the dose of drug administered was obtained. A normal milk ejection response was induced with a small dose of oxytocin injected immediately before nursing to mothers treated with PGF2α, indicating that the blocking effect was not due to a lack of mammary gland response. Two groups of mothers were injected with 40 μg PGF2α 2 and 4 h respectively before suckling. In both groups milk ejection was partially but significantly inhibited. In rats pre-treated with sodium pentobarbitone (3·5 mg/100 g body wt) to prevent the release of oxytocin induced by suckling, PGF2α (10 or 20 μg) did not modify the inhibition of milk ejection indicating that PGF2α does not have milk-ejecting activity. The administration of oxytocin to anaesthetized rats, immediately before a second suckling period, induced a normal milk-ejection response while in the rats treated with PGF2α, oxytocin was less effective. The results indicate that PGF2α inhibited milk ejection by a central block on oxytocin release and that the lipid is not able to mimic peripherally the milk-ejecting activity of oxytocin.


1991 ◽  
Vol 129 (3) ◽  
pp. 343-350 ◽  
Author(s):  
G. A. Jahn ◽  
R. P. Deis

ABSTRACT The part played by the adrenergic system on the release of prolactin and lactogenesis induced by prostaglandin F2α and the antiprogesterone RU 486 was studied in pregnant rats. Two doses of prostaglandin F2α (150 μg) administered at 08.00 and 12.00 h on day 19 of pregnancy induced, at 12.00 h on day 20 (24 h after administration), a significant increase in the serum concentration of prolactin, with a significant decrease in serum progesterone levels. These hormonal changes significantly augmented casein and lactose levels in the mammary gland. Treatment with RU 486 (2 mg/kg) at 08.00 h on day 19 augmented casein and lactose concentrations in the mammary gland at 12.00 h on day 20 without modifying serum concentrations of prolactin and progesterone. The adrenergic antagonists, propranolol (3 mg/kg), metoprolol (10 mg/kg), ICI 118 551 (200 μg/kg), idazoxan (100 μg/kg) and prazosin (10 mg/kg), were administered s.c. at 12.00 and 20.00 h on day 19 and 08.00 h on day 20 of pregnancy to intact rats or to rats previously treated with RU 486 or prostaglandin F2α. These adrenergic antagonists did not modify serum prolactin or progesterone levels in intact or RU 486-treated rats, but serum prolactin levels in the prostaglandin F2α-treated group were significantly reduced by treatment with propranolol, metoprolol or prazosin. In addition, propranolol and ICI 118 551 also decreased the casein and lactose concentrations in the mammary glands of RU 486- and prostaglandin F2α-treated rats, while the other compounds had no effect. We also studied the effect of adrenergic antagonists on the release of prolactin and lactogenesis induced by the physiological decrease in progesterone at the end of pregnancy. On day 21 of pregnancy at 18.00 h, serum progesterone levels in intact rats were lower than 40 nmol/l, while serum prolactin and casein and lactose concentrations in the mammary gland were higher compared with values measured at 12.00 h on day 20. Treatments with propranolol, metoprolol or prazosin administered at 20.00 h on day 20 and 08.00 and 14.00 h on day 21 of pregnancy were capable of significantly reducing serum prolactin concentrations while only propranolol decreased mammary casein and lactose. The effect of propranolol was not mediated through a reduction in serum placental lactogen measured by Nb2 lymphoma cell bioassay. These results show that the adrenergic system participates, through α1 and β1 receptors, in the regulation of prolactin release induced by the decrease in progesterone in pregnant rats. They also show that β2-adrenergic receptors play a role in the induction of casein and lactose synthesis in the mammary gland. Journal of Endocrinology (1991) 129, 343–350


1974 ◽  
Vol 63 (1) ◽  
pp. 13-20 ◽  
Author(s):  
NELIA T. VERMOUTH ◽  
R. P. DEIS

SUMMARY Ovariectomy of rats on day 19 of pregnancy induced a rapid rise in serum prolactin. Levels were significantly increased 4 h after removal of the ovaries and continued to rise up to 24 h. A transient fall occurred at 32 h, but serum prolactin concentration was still raised after 36, 48 and 58 h. Similar increases of serum prolactin occurred after ovariectomy on days 17 and 18 of pregnancy. Lactogenesis occurred 24·8 or 28·2 h after ovariectomy on days 19 or 17–18 of pregnancy respectively. Rats ovariectomized on day 17 or 18 delivered on day 21 and rats ovariectomized on day 19 delivered on day 22 of pregnancy. Ovariectomy impaired parturition in all groups. Treatment with oestrogen immediately after the operation did not prevent the rise in serum prolactin levels 4, 8 and 12 h after ovariectomy, but 24 h after ovariectomy, prolactin values were not significantly different from those in sham-operated control rats. When oestrogen was injected 12 h after ovariectomy, serum prolactin was markedly increased 12 h later. Lactogenesis occurred about 22·9 h after oestrogen treatment and all animals delivered on day 21 of pregnancy. Progesterone treatment prevented the rise in prolactin levels observed 4 and 8 h after ovariectomy, but at 12 h levels had risen and were similar to those observed in untreated ovariectomized rats. Progesterone prevented lactogenesis for 14 h (around 37.5 h after ovariectomy) and induced a delay in the onset of parturition. The results indicate that the decrease of progesterone in the blood after ovariectomy in pregnant rats may induce a release of prolactin and lactogenesis. Oestrogen seems to be effective in raising prolactin levels at low blood concentrations of progesterone.


1983 ◽  
Vol 99 (2) ◽  
pp. 181-187 ◽  
Author(s):  
P. Södersten ◽  
S. Hansen ◽  
P. Eneroth

Injection of 2·5 mg of the dopamine receptor antagonist domperidone raised serum prolactin concentrations within 3 h and high prolactin levels were maintained for 12 h in ovariectomized rats pretreated with 2 μg oestradiol benzoate (OB). This dose of domperidone stimulated the display of sexual behaviour in ovariectomized OB-treated rats within 3 h of administration. The behavioural effect of domperidone, but not its effect on serum prolactin concentrations, was blocked by adrenalectomy. Daily treatment with domperidone had no inhibitory effect on the subsequent induction of sexual behaviour by OB and progesterone in ovariectomized rats. A slight facilitation of the behaviour was noticed in OB-treated rats given daily domperidone injections, but this effect was cancelled by adrenalectomy. The results suggest that an acute increase in serum prolactin levels has no effect on the induction of sexual behaviour by OB in itself, but can stimulate the secretion of an adrenal product, perhaps progesterone, which facilitates the behaviour. Similarly, constant high levels of prolactin by themselves have no effect on the subsequent induction of sexual behaviour by OB and progesterone.


1987 ◽  
Vol 112 (3) ◽  
pp. 367-374 ◽  
Author(s):  
G. A. Jahn ◽  
R. P. Deis

ABSTRACT The effect of para-chlorophenylalanine (pCPA), an inhibitor of serotonin synthesis, on prolactin release was studied in rats on the day of pro-oestrus and at the end of pregnancy (day 19). The surges of prolactin normally seen in the afternoon of pro-oestrus in intact rats and in rats ovariectomized on dioestrous day 2 and primed with oestrogen were significantly inhibited by pCPA treatment. Administration of 5-hydroxy-tryptophan reversed the inhibitory action of pCPA on prolactin release. Treatment with progesterone also completely reversed the inhibitory effect of pCPA on prolactin release in pro-oestrous rats and partially reversed it in ovariectomized oestrogen-treated rats. Ovariectomy on day 19 of pregnancy induced a significant release of prolactin 12 and 24 h later. Administration of pCPA on day 18 of pregnancy produced a marked increase in serum concentrations of prolactin on days 19 and 20 in rats left intact or ovariectomized on day 19. Administration of 5-hydroxy-tryptophan significantly reversed this stimulatory effect of pCPA on prolactin release but did not modify the release of prolactin induced by ovariectomy. Methiothepin (1-[10,11-dihydro-8-(methylthio) <b,f> thiepin-10,41]-4-methylpiperazine maleate), a serotonin receptor blocker, also induced a significant increase in serum concentrations of prolactin on day 20 of pregnancy in rats left intact or ovariectomized on day 19. These results suggest the existence of different serotoninergic actions in the regulation of prolactin release at pro-oestrus and in late pregnancy. Serotonin facilitates the surges of serum prolactin released at pro-oestrus and in ovariectomized rats treated with oestrogen; progesterone enhances this effect. On the other hand, during late pregnancy, when progesterone tonically inhibits prolactin release, serotonin inhibits the release of prolactin. J. Endocr. (1987) 112, 367–374


1965 ◽  
Vol 31 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Y. SHINDE ◽  
K. ÔTA ◽  
A. YOKOYAMA

SUMMARY The time of initiation of copious milk secretion in the mammary glands of pregnant rats and the effects of removal of ovaries and/or placentae with foetuses on lactogenesis were investigated by measuring the lactose content of the mammary glands. In the normal pregnant rat, lactose was detected in the mammary gland on the 20th day of pregnancy, but not on the 15th. An abrupt increase in lactose content occurred on the 21st day of pregnancy. Bilateral or unilateral ovariectomy, and Caesarean section, with or without ovariectomy, performed on the 18th or 19th day of pregnancy all resulted in a marked increase in the lactose content on the 2nd day after operation. Bilateral ovariectomy caused early delivery of the young and lactose content in the gland increased further after delivery. Foetuses in the unilaterally ovariectomized rats were retained normally to term. Possible participation of placentae and foetuses in the mechanism of lactogenesis in pregnant animals by controlling the activity of the ovary is discussed.


1982 ◽  
Vol 92 (1) ◽  
pp. 37-42 ◽  
Author(s):  
H. M. A. MEIJS-ROELOFS ◽  
P. KRAMER ◽  
L. GRIBLING-HEGGE

A possible role of 5α-androstane-3α,17β-diol (3α-androstanediol) in the control of FSH secretion was studied at various ages in ovariectomized rats. In the rat strain used, vaginal opening, coincident with first ovulation, generally occurs between 37 and 42 days of age. If 3α-androstanediol alone was given as an ovarian substitute, an inhibitory effect on FSH release was evident with all three doses tested (50, 100, 300 μg/100 g body wt) between 13 and 30 days of age; at 33–35 days of age only the 300 μg dose caused some inhibition of FSH release. Results were more complex if 3α-androstanediol was given in combined treatment with oestradiol and progesterone. Given with progesterone, 3α-androstanediol showed a synergistic inhibitory action on FSH release between 20 and 30 days of age. However, when 3α-androstanediol was combined with oestradiol a clear decrease in effect, as compared to the effect of oestradiol alone, was found between 20 and 30 days of age. Also the effect of combined oestradiol and progesterone treatment was greater than the effect of combined treatment with oestradiol, progesterone and 3α-androstanediol. At all ages after day 20 none of the steroid combinations tested was capable of maintaining FSH levels in ovariectomized rats similar to those in intact rats. It is concluded that 3α-androstanediol might play a role in the control of FSH secretion in the immature rat, but after day 20 the potentially inhibitory action of 3α-androstanediol on FSH secretion is limited in the presence of oestradiol.


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