Potentiation by prolactin of the luteotrophic effect of oestradiol in the pregnant rat

1982 ◽  
Vol 101 (2) ◽  
pp. 287-292 ◽  
Author(s):  
Richard G. Rodway ◽  
David R. Garris

Abstract. The luteotrophic effects of elevated prolactin levels with or without concomitant oestradiol treatment were investigated in the pregnant rat after hysterectomy or hysterectomy plus hypophysectomy. On day 2 of pregnancy, rats were given a single pituitary transplant beneath the renal capsule and were subsequently hysterectomised on day 12. This treatment delayed the next ovulation (as judged by vaginal di-oestrus length) compared to sham-transplanted controls, but did not prevent the fall in serum progesterone concentrations (i.e. luteolysis) resulting from hysterectomy. The administration of 1 or 2 pituitary homo-transplants on day 12 at the time of hysterectomy again prolonged the di-oestrus length but did not prevent subsequent luteolysis. However, daily treatment with 100 μg of oestradiol given to rats which received 2 pituitary transplants on day 2 and which were then hysterectomised on day 12, did result in a maintenance of serum progesterone levels compared to those of oil-treated controls. In a separate study, pregnant rats were hysterectomised and hypophysectomised on day 12. Administration of either 1 or 2 pituitary transplants failed to maintain luteal function. However, concomitant daily treatment with 100 μg of oestradiol from day 12 onward prevented luteolysis and re-instated the day 12–16 rise in serum progesterone common to the intact pregnant rat. Progesterone levels then declined slowly until the end of the sampling period (day 23). Serum prolactin concentrations rose steadily for the first 10 days after insertion of pituitary transplants on day 12 of pregnancy. These data indicate that prolactin and oestradiol can act synergistically to stimulate progesterone secretion from the rat corpus luteum but only in the absence of the in situ pituitary; the effect is not seen unless hypophysectomy has been performed.

1983 ◽  
Vol 99 (2) ◽  
pp. 189-197 ◽  
Author(s):  
P. Södersten ◽  
S. Hansen ◽  
P. Eneroth

Treatment with oestradiol benzoate (OB; 2–250 μg) and progesterone (0·5–25 mg) failed to induce sexual behaviour in lactating rats 6 days after parturition. Removal of pups permitted the induction of sexual behaviour by OB and progesterone and the inhibitory effect of the presence of pups was proportional to the number present. Ovariectomy of lactating rats or reduction of serum prolactin levels in intact lactating rats by daily treatment with the dopamine receptor agonist bromocriptine (0·5 mg/day) permitted the induction of sexual behaviour despite the presence of suckling pups. Removal of pups from lactating rats and subsequent maintenance of high prolactin levels by daily treatment with the dopamine receptor antagonist domperidone (2·5 mg/day) maintained the state of refractoriness to the behavioural effects of OB and progesterone provided that the ovaries remained in situ. Inhibition of sexual behaviour in lactating rats could be maintained after ovariectomy by implantation of progesterone-filled, but not androgen-filled implants at the time of ovariectomy. Removal of the pups or reduction of prolactin levels by bromocriptine treatment permitted the induction of sexual behaviour by OB in ovariectomized progesterone-implanted lactating rats. Inhibition of the behaviour in ovariectomized progesterone-implanted lactating rats could be maintained after pup removal by daily domperidone treatment. Continuously raised serum progesterone or prolactin levels have no effect on the induction of sexual behaviour in female rats but the present data suggest that during lactation progesterone and prolactin act in synergy to inhibit the behaviour.


1994 ◽  
Vol 140 (1) ◽  
pp. 97-102 ◽  
Author(s):  
M Soaje ◽  
R P Deis

Abstract It is well known that the fall in serum progesterone concentrations during late pregnancy induces prolactin secretion in rats. On day 19 of pregnancy, administration of 10 mg of the antiprogesterone RU-486/kg induced a small but significant increase in serum prolactin. A lower dose (2 mg/kg) was not effective. Administration of naloxone (2 mg/kg) to pregnant rats on day 19 of pregnancy did not modify circulating prolactin but, after RU-486 treatment, a notable increase in serum prolactin was obtained 30 min after naloxone was given. The lack of effect of naloxone-methobromide in pregnant rats pretreated with RU-486 may indicate that the opioid-induced prolactin suppression acts centrally, most probably at the hypothalamic level. During day 21 of pregnancy, the time-course of prolactin secretion, measured at 0900, 1400, 1900 and 2200 h, was inversely correlated with circulating progesterone levels. At 0900 h, serum prolactin was very low with high serum progesterone concentrations but a significant increase in serum prolactin occurred at 2200 h; this was coincident with a significant decrease in the steroid. The stimulatory effect of naloxone on prolactin secretion was clearly dependent on the circulating progesterone level. Thus, at 1900 h of day 21, naloxone induced a significant increase in serum prolactin but, at 2200 h, the opioid antagonist dramatically enhanced the circulating level of prolactin. The serum prolactin increase induced by naloxone at 1900 h was prevented by the s.c. administration of 5 mg progesterone given 7 h earlier. Similarly, the large increase in serum prolactin levels at 1800 h on day 19 of pregnancy, after administration of RU-486 plus naloxone, was completely abolished by treatment with CB154. The lack of effect of RU-486 and naloxone on serum prolactin levels in virgin rats on the day of pro-oestrus demonstrates that the effect of naloxone on prolactin in pregnant rat is peculiar to the end of pregnancy. In conclusion, the attenuation of the central inhibitory action of progesterone facilitates the release of prolactin which is dramatically enhanced by naloxone treatment. These results provide an important new insight into the existence of a neuromodulatory regulation of prolactin secretion by the opioid system showing a paradoxical opioid-induced prolactin suppression at the end of pregnancy. Journal of Endocrinology (1994) 140, 97–102


1996 ◽  
Vol 150 (3) ◽  
pp. 423-429 ◽  
Author(s):  
C O Stocco ◽  
R P Deis

Abstract The mechanisms associated with the onset of luteolysis in the pregnant rat are not well known. The effect of a specific rat LH antiserum (AS-rLH) and of ovine LH (oLH) on luteal steroidogenesis on day 19 of pregnancy was examined. Rat LH antiserum administered intrabursally at 1000–1100 h on day 19 of pregnancy prevented the physiological decrease in 3β-hydroxysteroid dehydrogenase (3β-HSD) activity, the increase in 20α-hydroxysteroid dehydrogenase (20α-HSD) activity and the fall in serum progesterone (P4) level observed at 1800 h on day 21 of pregnancy. To see if oLH has a direct effect on luteal steroidogenesis, the gonadotrophin was injected into the periovarian bursa. The intrabursa treatment with 1 μg oLH on day 19 of pregnancy at 0800–0900 h did not modify corpus luteal function 36 h after treatment, but treatment with 4 μg oLH per ovary induced a significant progressive decrease in luteal 3β-HSD activity starting 12 h after treatment, while a significant increase in 20α-HSD activity, concomitant with a decrease in serum P4 level, occurred 48 h after treatment. Luteal P4 content decreased with respect to control groups 36 and 48 h after intrabursal treatment with 4 μg oLH. The intrabursal administration of 8 μg oLH induced an increase in 20α-HSD activity and a decrease in 3β-HSD activity 36 h after treatment. Administration of 4 μg oLH per ovary on day 8 of pregnancy induced a significant increase in serum P4 levels without modifying 3β-HSD activity. In rats treated with oLH on day 19 of pregnancy the decrease in 3β-HSD activity occurred 36 h before the significant increase in 20α-HSD activity and serum P4 level. In conclusion, the luteal enzymatic activity changes and the significant decrease in the intraluteal P4 concentration induced by the intrabursal administration of oLH and the clear effect of AS-rLH preventing the physiological luteal changes preceding parturition provide good evidence of an intraovarian action of LH during the normal progression of luteolysis in late pregnant rats. Journal of Endocrinology (1996) 150, 423–429


1975 ◽  
Vol 13 (5) ◽  
pp. 541-545 ◽  
Author(s):  
David J. Elbaum ◽  
Edward M. Bender ◽  
Judith M. Brown ◽  
P. Landis Keyes

1973 ◽  
Vol 57 (1) ◽  
pp. 63-74 ◽  
Author(s):  
I. ROTHCHILD ◽  
R. B. BILLIAR ◽  
I. T. KLINE ◽  
G. PEPE

SUMMARY To test the hypothesis of Raj & Moudgal (1970) that luteinizing hormone (LH) is the essential luteotrophin during pregnancy in the rat, pregnant rats were hypophysectomized and hysterectomized on either day 12 or day 15 of pregnancy, and the changes in peripheral serum progesterone level measured. The serum progesterone level remained at approximately the day-12 value for 3 days after hypophysectomy and hysterectomy on day 12, but fell drastically and remained low after the same operation on day 15, or in pseudopregnant rats operated on on day 12, or after removal of the ovaries from pregnant rats on day 12. Oestrogen treatment increased the serum progesterone level slightly in the pregnant rats after hypophysectomy and hysterectomy, but not after ovariectomy; it had no effect in the pseudopregnant rats, with or without deciduomata, or in lactating rats nursing litters of seven to nine pups. The corpora lutea stopped growing or slowly regressed soon after hypophysectomy—hysterectomy in all except the pregnant rats operated on on day 12 and treated with oestrogen, and in these growth was very slight. The luteal content of progesterone did not change for 3 days after hypophysectomy—hysterectomy on day 12 of pregnancy, and fell slightly thereafter. The metabolic clearance rate of progesterone was not significantly changed by hypophysectomy—hysterectomy. It thus appears that true secretion of progesterone continues in pregnant rats for about 3 days after day 12 in the absence of the pituitary and placentas, but at a much lower rate than that found in intact, or in day-12 hypophysectomized pregnant rats (Pepe & Rothchild, 1972a). The placental luteotrophin thus seems to increase the rate of progesterone secretion in the absence of LH. The results do not seem to fit with the hypothesis that LH is essential for progesterone secretion.


1983 ◽  
Vol 97 (2) ◽  
pp. 283-290 ◽  
Author(s):  
L. M. Williams ◽  
M. Hollingsworth ◽  
M. Dukes ◽  
I. D. Morris

Fluprostenol, an analogue of prostaglandin F2α, administered s.c. to rats on day 18 of pregnancy increased cervical creep, or softness, by the following day. Doses of fluprostenol 100-fold larger were necessary to increase uterine contractions. Fluprostenol produced falls in serum progesterone concentrations, increases in 20α-dihydroprogesterone concentrations, no changes in oestradiol or relaxin concentrations and a reduction in the ovarian human chorionic gonadotrophin binding capacity in vitro. Fluprostenol was less potent in inducing cervical softness when administered per vaginam, and a dose which produced softening in pregnant rats was ineffective in ovariectomized steroid-maintained pregnant or pro-oestrous rats. The findings suggest that cervical softening by fluprostenol does not result from a simple direct action on the cervix or by increasing uterine contractions, but rather by an indirect hormonal action mediated by the ovaries. The results with the lowest dose of fluprostenol indicate that cervical softening could be produced without a sustained fall in serum progesterone concentrations. Fluprostenol is much more potent at increasing cervical softness in the pregnant rat than prostaglandin F2α or prostaglandin E2. With fluprostenol the ratio of dose to induce uterine contractility relative to that to produce cervical softness was greater than with these natural prostaglandins, indicating the greater selectivity of fluprostenol in the pregnant rat.


1972 ◽  
Vol 52 (3) ◽  
pp. 413-418 ◽  
Author(s):  
N. R. MOUDGAL ◽  
H. R. BEHRMAN ◽  
R. O. GREEP

SUMMARY The effect of a single injection of luteinizing hormone (LH) antiserum on ovarian progesterone and 20α-dihydroprogesterone in day-8 and day-15 pregnant rats was studied. Within 24 h of an injection of LH antiserum, progesterone secretion was reduced by 80% in day-8 and by 25% in day-15 pregnant rats. The 20α-dihydroprogesterone levels after antiserum treatment were markedly increased in rats which were 8 days pregnant but reduced in rats which were 15 days pregnant. The free cholesterol content of the ovary did not change after antiserum injection but the cholesteryl ester content markedly increased. It is thus apparent that neutralization of endogenous LH resulted in a significant reduction in the progesterone secretion of the corpus luteum of the pregnant rat. The significance of these results is discussed.


1982 ◽  
Vol 94 (1) ◽  
pp. 21-27 ◽  
Author(s):  
R. S. Bridges ◽  
R. B. Todd ◽  
C. M. Logue

Testosterone concentrations in serum of rats bled throughout pregnancy and post partum were measured using Celite microcolumn chromatography and a radioimmunoassay for testosterone. Mean serum levels of testosterone ranged from about 170 to 340 pmol/l during the first 10 days of pregnancy. Significant increases in concentrations of testosterone in serum of pregnant rats were found on days 12, 15 and 18 of gestation. The highest testosterone concentrations occurred on days 18 and 20 of pregnancy when mean levels were 3228 and 3685 pmol/l respectively. Testosterone levels declined before parturition on day 22 (mean = 1449 pmol/l and declined further after parturition (mean = 315 pmol/l). In order to determine whether serum testosterone concentrations varied during the day in the pregnant rat, samples were collected at 6-h intervals on days 6–7 and 14–15 of gestation. Diurnal variations in serum testosterone concentrations were not evident during early or late pregnancy, unlike the rhythmic changes in serum prolactin levels found at these times during early pregnancy. The possible sources of the increased titres of serum testosterone during the second part of gestation in rats are discussed.


1982 ◽  
Vol 94 (1) ◽  
pp. 61-67 ◽  
Author(s):  
B. J. Waddell ◽  
N. W. Bruce ◽  
J. K. Olynyk

We have sought to determine whether the rate of ovarian progesterone secretion in pregnant rats is inversely related to the arterial plasma progesterone concentrations. For this purpose, rates of ovarian progesterone secretion were measured on day 16 of pregnancy in seven progesterone-treated and eight untreated rats. Treated rats received once-daily s.c. injections of 63·6 μmol progesterone in peanut oil on days 13 to 16. In a separate experiment, this treatment was found to produce a relatively stable fivefold increase in plasma progesterone concentrations. The rate of ovarian blood flow was increased in treated animals (mean ± s.e.m.; treated, 0·63± 0·08 ml/min; untreated, 0·43± 0·08 ml/min) but the progesterone secretion rate was unchanged (treated, 1·13 ± 0·20 μmol/day per ovary; untreated, 1·05 ± 0·15 μmol/day per ovary). The stability of the progesterone secretion rate in the face of a fivefold increase in plasma progesterone concentration implies a lack of negative feedback from progesterone in plasma in the regulation of ovarian progesterone secretion.


2011 ◽  
Vol 301 (5) ◽  
pp. R1418-R1426 ◽  
Author(s):  
B. G. White ◽  
D. J. MacPhee

The uterine musculature, or myometrium, demonstrates tremendous plasticity during pregnancy under the influences of the endocrine environment and mechanical stresses. Expression of the small stress protein heat shock protein B1 (HspB1) has been reported to increase dramatically during late pregnancy, a period marked by myometrial hypertrophy caused by fetal growth-induced uterine distension. Thus, using unilaterally pregnant rat models and ovariectomized nonpregnant rats with uteri containing laminaria tents to induce uterine distension, we examined the effect of uterine distension on myometrial HspB1 expression. In unilaterally pregnant rats, HspB1 mRNA and Ser15-phosphorylated HspB1 (pSer15 HspB1) protein expression were significantly elevated in distended gravid uterine horns at days 19 and 23 (labor) of gestation compared with nongravid horns. Similarly, pSer15 HspB1 protein in situ was only readily detectable in the distended horns compared with the nongravid horns at days 19 and 23; however, pSer15 HspB1 was primarily detectable in situ at day 19 in membrane-associated regions, while it had primarily a cytoplasmic localization in myometrial cells at day 23. HspB1 mRNA and pSer15 HspB1 protein expression were also markedly increased in ovariectomized nonpregnant rat myometrium distended for 24 h with laminaria tents compared with empty horns. Therefore, uterine distension plays a major role in the stimulation of myometrial HspB1 expression, and increased expression of this small stress protein could be a mechanoadaptive response to the increasing uterine distension that occurs during pregnancy.


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