Opioidergic regulation of prolactin secretion during pregnancy: role of ovarian hormones

1997 ◽  
Vol 155 (1) ◽  
pp. 99-106 ◽  
Author(s):  
M Soaje ◽  
RP Deis
Keyword(s):  
Ovarian Hormones ◽  
Prolactin Secretion ◽  
High Serum ◽  
Opioid System ◽  
Serum Prolactin ◽  
Stimulatory Action ◽  
Serum Progesterone ◽  
Naloxone Administration ◽  
Ru 486 ◽  
Naloxone Treatment

We have recently demonstrated 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. The aim of this study was to determine a possible interaction between the opioid system and ovarian hormones on the release of prolactin during pregnancy. Serum prolactin levels measured at 1800 h were significantly higher on days 3 and 6 of pregnancy when compared with the other days of gestation. These increases in serum prolactin were reduced significantly by naloxone (2 mg/kg) administered at 1730 h and by RU-486 (10 mg/kg) administered at 0800 h. The response induced by RU-486 was potentiated by naloxone only on day 3. On days 7, 13 and 16, prolactin secretion was not modified by RU-486 and/or naloxone treatment. In RU-486 pretreated rats, naloxone administration increased serum prolactin levels only on day 16 of pregnancy. Interestingly, progesterone treatment (0.5 mg/rat) on days 13, 14 and 15 of pregnancy prevented the high increase in serum prolactin induced by RU-486 and naloxone on day 16 of pregnancy. The progressive increase and decrease of serum progesterone concentration during pregnancy was not modified by naloxone treatment. The participation of oestrogen in the regulation of prolactin secretion by the opioid system on days 3, 16 and 19 was examined by treating these groups of rats with oestradiol benzoate or tamoxifen citrate. Oestradiol (2 micrograms/rat) significantly increased serum prolactin levels on day 3 and naloxone administration did not modify this increase. No effect was observed after oestradiol (5 micrograms/rat) and naloxone treatment on days 16 and 19 of pregnancy. Oral administration of tamoxifen (500 micrograms/kg) the previous day did not modify the serum prolactin concentration measured at 1800 h in oil-treated rats on days 3, 16 and 19 of pregnancy. The antioestrogen completely abolished the naloxone-induced prolactin secretion on day 16 in rats pretreated with RU-486 but no effect was observed on day 19. When tamoxifen was administered on days 14 and 15 of pregnancy, the high serum prolactin levels on day 19 induced by treatment with RU-486 and naloxone were significantly reduced. In conclusion, these results provide an important new insight into the existence of a dual neuromodulatory regulation of prolactin secretion by the opioid system during pregnancy. After a stimulatory action during the first days, there is a change to an inhibitory control at the end of pregnancy, starting around day 16. Moreover, the activation of the inhibitory modulation of the opioid system on prolactin secretion on days 16 and 19 of pregnancy seems to be mediated by changes in the oestrogen and progesterone action.

A modulatory role of endogenous opioids on prolactin secretion at the end of pregnancy in the rat

1994 ◽  
Vol 140 (1) ◽  
pp. 97-102 ◽  
Author(s):  
M Soaje ◽  
R P Deis
Keyword(s):  
Time Course ◽  
Prolactin Secretion ◽  
Endogenous Opioids ◽  
Opioid Antagonist ◽  
Serum Prolactin ◽  
Serum Progesterone ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Ru 486 ◽  
Prolactin Suppression

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

scholarly journals Regulation by endogenous opioids of suckling-induced prolactin secretion in pregnant and lactating rats: role of ovarian steroids

2002 ◽  
Vol 172 (2) ◽  
pp. 255-261 ◽  
Author(s):  
M Soaje ◽  
EG de Di Nasso ◽  
RP Deis
Keyword(s):  
Inhibitory Effect ◽  
Prolactin Secretion ◽  
Endogenous Opioids ◽  
Opioid System ◽  
Serum Prolactin ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Subsequent Increase ◽  
Stimulatory Action

Evidence suggests that endogenous opioid peptides are implicated in the suckling-induced prolactin rise. We explored the role of the opioid system and the participation of ovarian hormones in the regulation of prolactin induced by the suckling stimulus at the end of pregnancy in rats with developed maternal behavior, and during lactation. Suckling for 24 h induced a significant increase in serum prolactin on day 19 of pregnancy, which was increased more than three times when naloxone (2 mg/kg s.c.) or mifepristone (2 mg/kg) was administered. The combination of naloxone and mifepristone did not increase serum prolactin more than either compound alone. Administration of tamoxifen (500 microg/kg orally) on days 14 and 15 of pregnancy completely abolished the effect of naloxone, indicating a role for estrogens in establishing this inhibitory role of opioids. To examine the participation of the opioid system during lactation, we used groups of rats on days 1, 3, 5, 12 and 19 postpartum either (i) isolated from the pups for 4 h, or (ii) isolated from the pups for 3.5 h and reunited with them and suckled for 30 min. Naloxone, given just before replacing the pups, prevented the increase in serum prolactin levels observed in the suckled group of rats but had no effect on the basal levels of the isolated rats. To examine whether the participation of the opioid system in the release of prolactin is dependent on the variation of progesterone levels, rats on day 20 of pregnancy were implanted with two cannulae containing progesterone (that blocked postpartum ovulation) or cholesterol, and cesarean surgery was performed on day 21. To maintain lactation, pups (1-3 days old) were replaced every 24 h, and 4 days after the cesarean eight pups were placed in the cage at 1800 h to maintain a strong suckling stimulus during the following 24 h. Naloxone administration significantly reduced serum prolactin levels in control (cholesterol) rats but progesterone implants prevented the inhibitory effect of naloxone and this effect was not modified by treatment with estrogen. These results indicate that the opioid system modulates suckling-induced prolactin secretion, passing from an inhibitory action before delivery to a stimulatory action during lactation. This regulatory shift seems to be dependent on the fall in progesterone concentration at the end of pregnancy and the subsequent increase after the postpartum ovulation and luteal phase.

PROLACTIN-LOWERING EFFECT OF LOW DOSES OF LISURIDE IN MAN

1978 ◽  
Vol 87 (2) ◽  
pp. 234-240 ◽  
Author(s):  
R. Horowski ◽  
H. Wendt ◽  
K.-J. Gräf
Keyword(s):  
Prolactin Secretion ◽  
High Serum ◽  
Serum Prolactin ◽  
Low Doses ◽  
Predominant Role ◽  
Lowering Effect ◽  
Healthy Female ◽  
Dopaminergic Mechanisms ◽  
Ergot Derivative

ABSTRACT Lisuride, a new semisynthetic ergot derivative, effectively decreased the TRH-induced hyperprolactinaemia in healthy female volunteers at a dose of 300 μg given orally. Basal prolactin levels were suppressed after a single dose of 100 and 200 μg lisuride. This effect was still present 6 h after administration. Two hundred μg lisuride also decreased the high serum prolactin levels produced by im injection of 50 mg sulpiride, and conversely, sulpiride injection abolished the prolactin lowering effect of lisuride. These results demonstrate that in man too lisuride is a very potent prolactin-lowering agent. In addition, the data support the hypothesis of a predominant role of dopaminergic mechanisms in the regulation of prolactin secretion.

EFFECTS OF TWO SUBSTITUTED BENZAMIDES, TIAPRIDE AND SULTOPRIDE, ON GONADOTROPHINS AND PROLACTIN

1978 ◽  
Vol 89 (1) ◽  
pp. 29-37 ◽  
Author(s):  
M. L'Hermite ◽  
R. M. MacLeod ◽  
C. Robyn
Keyword(s):  
Pituitary Gland ◽  
Pituitary Tumour ◽  
Prolactin Secretion ◽  
High Serum ◽  
Serum Prolactin ◽  
Acute Effects ◽  
Substituted Benzamides ◽  
Normal Men

ABSTRACT The acute effects in the human of tiapride and sultopride, two new substituted benzamides related to sulpiride, were studied with respect to gonadotrophins (LH and FSH) and prolactin (PRL) secretion. Two different groups of 3 normal men and 3 normally cycling women received im injections of either 100 mg sultopride or 200 mg tiapride. Five min after the injection of either psychotropic drug, the serum PRL concentration increased significantly (P < 0.001 by variance analysis) and reached maximal values by 30 min and remained elevated for at least 6 h; women tended to release more prolactin than men. Although tiapride (500 nm) had no direct effect on the in vitro synthesis or secretion of prolactin, the drug blocked the inhibitory action of dopamine (500 nm) on the secretion of prolactin. Rats bearing a transplantable prolactin-secreting pituitary tumour MtTW15 have extremely high serum prolactin and through an autofeed mechanism the host's pituitary gland is suppressed. The in vitro synthesis and secretion of prolactin by these rats' pituitary gland is decreased. The in vivo administration of tiapride to these tumour-bearing rats restored the in vitro secretion of prolactin to control values. The in vitro data support the concept that tiapride increases prolactin secretion directly at the pituitary level by blocking the inhibitory activity of dopamine; an additional effect at a higher level can not, however, be ruled out. In vivo in the human, no significant modification of LH and FSH occurred after either drug, suggesting that the menstrual cycle disturbances observed during chronic treatment with tiapride might be related to hyperprolactinaemia or be the result of a mechanism similar to that inducing hyperprolactinaemia.

Photoperiod effects on the development of beef heifers

2003 ◽  
Vol 83 (4) ◽  
pp. 721-730 ◽  
Author(s):  
J. A. Small ◽  
N. D. Glover ◽  
A. D. Kennedy ◽  
W. P. McCaughey ◽  
D. R. Ward
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Prolactin Secretion ◽  
Outdoor Environment ◽  
Serum Prolactin ◽  
Beef Heifers ◽  
Serum Progesterone ◽  
Ambient Temperatures ◽  
Natural Photoperiod ◽  
Sire Breed

Crossbred beef heifers (n = 144) were assigned at weaning (187 ± 14 d of age) by body weight (225 ± 23 kg) and sire breed (British/Continental) to one of two photoperiod treatments from 21 Decem ber 1998 (0 wk) until 10 May 1999 (20 wk): natural photoperiod (NP) that gradually increased from 8.1 h (0 wk) to 15.2 h (20 wk) and, extended photoperiod (EP) that consisted of natural + supplemental light (400 lx, 1 m above ground) to extend photoperiod to 16 h. Rations were formulated for two-steps of body weight gain (0.6 and 1.2 kg d-1) to achieve 60% of mature weight at 18 wk. Visual observations of estrus behavior were made twice daily and confirmed by serum progesterone. Body weight, backfat and serum prolactin data were determined for each 4-wk period. Ambient temperatures averaged -12.2 ± 6°C in winter (0 to 12 wk) and 4.2 ± 5°C in spring (12 to 20 wk). Gain in body weight was greater (P < 0.05) and backfat lower (P < 0.05) for EP than NP treatments from -2 to 6 wk and only 1% of heifers had attained puberty during this period. However, as yearlings at similar (P > 0.05) body weight and backfat, more (P < 0.05) EP than NP heifers had attained puberty (84.7% vs. 69.4%). Prolactin was greater (P < 0.05) for EP than NP treatments from 2 to 6 wk (10.3 vs 5.5 ± 1.2 ng mL-1). Management of photoperiod influences attainment of puberty and prolactin secretion in beef heifers housed in an outdoor environment. Key words: Photoperiod, puberty, estrus, beef heifers, prolactin

Involvement of the adrenergic system on the release of prolactin and lactogenesis at the end of pregnancy in the rat

1991 ◽  
Vol 129 (3) ◽  
pp. 343-350 ◽  
Author(s):  
G. A. Jahn ◽  
R. P. Deis
Keyword(s):  
Mammary Gland ◽  
Placental Lactogen ◽  
Serum Prolactin ◽  
Adrenergic System ◽  
Serum Progesterone ◽  
Pregnant Rats ◽  
Ru 486 ◽  
Prostaglandin F ◽  
Adrenergic Antagonists ◽  
Intact Rats

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

Feedback regulation by progesterone of stress-induced prolactin release in rats

1989 ◽  
Vol 120 (1) ◽  
pp. 37-43 ◽  
Author(s):  
R. P. Deis ◽  
E. Leguizamon ◽  
G. A. Jahn
Keyword(s):  
Prolactin Secretion ◽  
Female Rats ◽  
Male Rats ◽  
Serum Prolactin ◽  
Progesterone Concentration ◽  
Prolactin Release ◽  
Serum Progesterone ◽  
Progesterone Secretion ◽  
Male And Female Rats

ABSTRACT We have previously found that modifications to serum progesterone concentration have profound inhibitory effects on prolactin release in response to ether stress. The objective of the present study was to determine the effect of ether stress on progesterone secretion and the role of this steroid in ether-induced prolactin release. Serum progesterone concentration, 5 min after ether stress had been applied over a 2-min period, was consistently increased in male rats, in cyclic rats on the mornings of pro-oestrus and oestrus, and in androgenized rats in permanent oestrus. Ovariectomized androgenized rats showed the same response. Adrenalectomy of male and female rats abolished the progesterone increase induced by stress. Thus, the progesterone secreted by stressed rats is mostly of adrenal origin. In groups of male and pro-oestrous rats, circulating concentrations of prolactin and progesterone were measured from 5 to 60 min after stress. In both sexes the serum prolactin concentration was significantly increased at only 5 and 10 min after stress when compared with control values. In pro-oestrous rats the serum progesterone concentration was significantly higher than in controls at 5, 10 and 20 min after stress, whilst in male rats the concentration remained significantly higher at 30 min. Thirty minutes after the first stress, male and pro-oestrous rats were etherized for 2 min, and bled 5 min after removal from the ether container. In female rats this second stress produced only a slight but significant increase in serum prolactin concentrations, whereas in male rats prolactin concentrations did not increase. The second stress was still capable of significantly increasing circulating progesterone concentrations to levels similar to those obtained after the first stress in animals from all groups. Thus, an increased circulating progesterone concentration did not lead to regulation of further progesterone secretion. To find whether this type of response was due to a blocking effect of the previously released progesterone, animals were injected with the anti-progesterone RU 38486 (17β-hydroxy-11β-(4-dimethylaminophenyl)-17α-propinyl-oestra-4,9-dien-3-one) or with a specific antibody raised against progesterone. In both groups of treated rats the second stress induced a significant increase in serum prolactin and progesterone concentrations to give values similar to those obtained after the first stress. When the second stress was applied to female rats 60 min after the first the prolactin response was comparable to that obtained after the first exposure to ether. In conclusion, we have demonstrated that serum prolactin and progesterone concentrations are significantly increased after ether stress, and that the latter hormone exerts an inhibitory regulatory feedback on prolactin secretion. These results provide an important new insight into the role of progesterone in the regulation of prolactin release. Journal of Endocrinology (1989) 120, 37–43

Indomethacin treatment prevents prolactin-induced luteolysis in the rat

1987 ◽  
Vol 112 (2) ◽  
pp. 317-322 ◽  
Author(s):  
J. E. Sánchez-Criado ◽  
K. Ochiai ◽  
I. Rothchild
Keyword(s):  
Corpus Luteum ◽  
Left Kidney ◽  
Prolactin Secretion ◽  
Female Rats ◽  
Silicone Elastomer ◽  
Serum Prolactin ◽  
Corpora Lutea ◽  
Synthesis Inhibitor ◽  
Significant Difference ◽  
Indomethacin Treatment

ABSTRACT Adult female rats were hypophysectomized and their pituitary glands autotransplanted beneath the left kidney capsule on day 2 (day 1 was the day of ovulation). In such rats the pituitary secretes prolactin fairly constantly and the corpora lutea secrete progesterone for several months. To induce the luteolytic effect of prolactin the rats were first injected s.c. with 2-bromo-α-ergocryptine (CB-154) on cycle days 12, 13 and 14 (i.e. 10, 11 and 12 days after operation) to depress prolactin secretion, and then with CB-154 vehicle (70% ethanol) daily until cycle day 21, to allow prolactin secretion to resume. One ovary was removed from each rat on day 15 and the remaining one on day 22. The mean (± s.e.m.) weight of the corpora lutea on day 15 was 1·46±0·06 mg and 0·98±0·07 mg on day 22 (n = 17). In contrast, rats in which the CB-154 treatment was maintained to day 21 had corpora lutea which weighed 1·31 ±0·09 on day 15 and 1·47 ±0·08 mg on day 22 (n = 15). To investigate whether indomethacin, a prostaglandin synthesis inhibitor, affected the luteolytic action of prolactin, the experiment was repeated, but on day 15 (after the removal of one ovary) the groups in which CB-154 treatment was stopped, as well as the group in which CB-154 treatment was maintained, were each divided into two groups. In one, indomethacin-containing silicone elastomer wafers and, in the other, blank silicone elastomer wafers, were placed within the bursa of the remaining ovary. There were no differences in corpus luteum weight on day 15 among any of these groups and the two groups of the first experiment. There was no significant difference in corpus luteum weight between day 15 and day 22 in any of the six groups except for the two groups treated with the CB-154 vehicle and not with indomethacin. Thus, treatment with indomethacin prevented the fall in corpus luteum weight associated with the discontinuation of CB-154 treatment. Serum prolactin levels fell until day 15 in all rats and remained low in those in which the CB-154 treatment was maintained to day 21, but returned to control values in those treated with vehicle after day 14. Serum progesterone levels fell and remained low in all groups. Indomethacin treatment had no effect on the levels of either serum prolactin or progesterone. We conclude that some of the pharmacological effects of indomethacin are to prevent prolactin-induced luteolysis, and we suggest that prolactin induces rapid regression of the corpus luteum by stimulating intraluteal prostaglandin production or by being necessary for the effect of luteolytic prostaglandins. J. Endocr. (1987) 112, 317–322

Danazol and prolactin status in patients with endometriosis

1984 ◽  
Vol 107 (4) ◽  
pp. 445-449 ◽  
Author(s):  
A. M. Wallace ◽  
D. A. R. Lees ◽  
A. D. G. Roberts ◽  
C. E. Gray ◽  
E. H. McLaren ◽  
...  
Keyword(s):  
Prolactin Level ◽  
Prolactin Secretion ◽  
Normal Serum ◽  
Serum Prolactin ◽  
Serum Prolactin Level ◽  
Significant Drop ◽  
Increased Sensitivity ◽  
Danazol Therapy

Abstract. A group of 55 women with endometriosis was studied before and during danazol therapy. An unexpectedly high proportion (36%) had a raised serum prolactin level before treatment which was reduced after 50 days of danazol (before treatment 783 ± 333 mU/l; on danazol 243 ± 113 mU/l, P < 0.001). In contrast patients with normal serum prolactin levels showed no significant drop on danazol therapy. In all patients serum oestradiol was significantly reduced during treatment (before treatment 449 ± 188 pmol/l; on danazol 207 ± 117 pmol/l, P < 0.001). In one patient with hyperprolactinaemia danazol reduced both basal and stimulated prolactin levels, whereas in 5 women with normal prolactin levels we could detect no gross alteration in metoclopramide or TRH stimulated prolactin levels associated with danazol therapy. The possibility that normalisation of raised prolactin levels may be secondary to reduced oestrogens and that patients with endometriosis have an increased sensitivity to oestrogen-induced prolactin secretion is discussed.

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