Luteolytic and antiluteolytic effect of the antiprogestagen RU486 in pseudopregnant rats

1995 ◽  
Vol 145 (3) ◽  
pp. 449-454 ◽  
Author(s):  
J Th J Uilenbroek ◽  
P van der Schoot ◽  
J A M Mattheij ◽  
J J M Swarts
Keyword(s):  
Plasma Concentrations ◽  
Early Morning ◽  
Prolactin Secretion ◽  
Female Rats ◽  
Corpora Lutea ◽  
Serum Progesterone ◽  
Early Afternoon ◽  
Two Generations ◽  
Pituitary Glands ◽  
High Concentrations

Abstract To study the effects of the antiprogestagen RU486 on luteal activity in pseudopregnant rats, adult female rats made pseudopregnant by sterile copulation were given daily injections with oil vehicle or with RU486 (2 mg/day) either during the entire period of pseudopregnancy (day 1 till day 14) or during the second half of pseudopregnancy (day 8 till day 14). Blood was taken every other day to measure serum concentrations of progesterone. At autopsy, on day 15, the weights of ovaries, isolated corpora lutea and pituitary glands were recorded. In a second study using the same experimental protocol, blood was taken via a jugular vein cannula on days 8, 9, 10 and 11 after induction of pseudopregnancy; on each of these days blood samples were taken at 0700, 0800 and 0900 h, and at 1700, 1800 and 1900 h to measure plasma concentrations of prolactin, LH and progesterone. Administration of RU486 from day 1 of pseudopregnancy onwards had no effect on the increasing concentrations of serum progesterone during the first half of pseudopregnancy. Thereafter progesterone concentrations increased further in RU486-treated rats whereas they decreased in oil-treated pseudopregnant rats. Administration of RU486 from day 8 of pseudopregnancy onwards resulted in a decline in progesterone concentrations in serum on day 10 followed by ovulation on day 11. Plasma LH concentrations in rats treated with RU486 from day 1 of pseudopregnancy were higher than those in oil-treated rats on days 8, 9, 10 and 11. Treatment from day 8 of pseudopregnancy resulted in low LH concentrations at days 8 and 9 and the presence of a preovulatory surge of LH on the afternoon of day 10 (day of pro-oestrus). Plasma concentrations of prolactin measured in oil-treated rats showed two daily surges of similar magnitude in the morning and afternoon of days 8, 9, 10 and 11. In animals treated with RU486 from day 8 onwards, the afternoon surge on day 9 and the morning surge on day 10 were absent. This demonstrated that the luteolytic effect of RU486 when given during the second part of pseudopregnancy is due to a blockade in the afternoon surge of prolactin on day 9. In animals treated with RU486 from day 1 of pseudopregnancy onwards, prolactin in the early morning samples was low, while prolactin in the afternoon samples was highly elevated. At autopsy on day 15, the weights of ovaries, corpora lutea and pituitary glands in animals treated with RU486 from day 1 were larger than those in oil-treated rats; this is in line with an increased secretion of prolactin. In contrast, in animals treated with RU486 from day 8, pituitary weight was not elevated and the increase in ovarian weight was due to the presence of two generations of corpora lutea. In conclusion, whether or not RU486 is luteolytic in pseudopregnant rats depends on the time of administration: injection during the second half of pseudopregnancy inhibits prolactin secretion and induces luteolysis, while administration during the early phase of pseudopregnancy results in high concentrations of prolactin in the early afternoon and therefore prevents luteolysis. Journal of Endocrinology (1995) 145, 449–454

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

Cell-density dependence of the rate of prolactin secretion from perifused rat anterior pituitary cells

1983 ◽  
Vol 97 (2) ◽  
pp. 221-228 ◽  
Author(s):  
A. M. Bentley ◽  
M. Wallis
Keyword(s):  
Density Dependence ◽  
Cell Density ◽  
Anterior Pituitary ◽  
Prolactin Secretion ◽  
Female Rats ◽  
Pituitary Cells ◽  
The Third ◽  
Pituitary Glands ◽  
Prolactin Content ◽  
Perifusion System

Anterior pituitary glands from female rats were dispersed enzymically in the absence of dopamine. Dispersed cells (106–107) were layered onto columns containing Bio-Gel P-2 and were then perifused for 3 h with Dulbecco's Modified Eagle's Medium. The prolactin content of the perifusate and cell homogenates was determined by radioimmunoassay. Prolactin secretion during the third hour of perifusion increased as the loading of cells increased. However, the increase was not linear, and when secretion rate per 106 cells was calculated it was found that increased loading decreased the rate, which fell to a plateau of 1·3 ± 0·1 (s.e.m.) ng/min per 106 cells at a loading of about 8 × 106 cells from 3·8 ± 0·1 ng/min per 106 cells for a loading of 106 cells. This cell-density dependence of the rate of prolactin secretion in the perifusion system may be due to intercellular contact since the isolation of the tissue removes the influence of hypothalamic factors, while localized build up of prolactin (potentially causing direct autoregulation on the lactotroph) seems unlikely because of the continuous flow of medium.

THE CORPUS LUTEUM-HYPOPHYSIS RELATIONSHIP: THE EFFECT OF PROGESTERONE TREATMENT ON THE RELEASE OF GONADOTROPHINS IN THE RAT

1966 ◽  
Vol 51 (2) ◽  
pp. 231-244 ◽  
Author(s):  
Andrew B. Kaufman ◽  
I. Rothchild
Keyword(s):  
Female Rats ◽  
Ovariectomized Rats ◽  
Corpora Lutea ◽  
Follicle Development ◽  
Significant Elevation ◽  
Once Daily ◽  
Progesterone Treatment ◽  
Gonadotrophin Secretion ◽  
Pituitary Glands ◽  
Weight Method

ABSTRACT The effect of progesterone on pituitary gonadotrophin release has been studied in the rat. Castrated female rats bearing ovarian autotransplants, or unilaterally ovariectomized rats, were given 1 to 5 mg of progesterone daily for intervals from 7 to 28 days, and then killed. The ovaries, uteri, and vaginas were examined grossly and microscopically, and the pituitary glands were assayed for total gonadotrophin content by the mouse uterine weight method. Although treatment with 5 mg of progesterone for 28 days inhibited ovulation, it did not prevent Graafian follicle development (determined histologically) or secretory function (evaluated by the presence of vaginal mucification) in either of the animal preparations. Progesterone treatment was associated with a significant elevation of pituitary gonadotrophic potency in the castrated rats bearing ovarian autotransplants, but not in the unilaterally ovariectomized rats. These findings suggest that the tonic rate of gonadotrophin secretion is unaffected by treatment with 5 mg of progesterone daily. The acute discharge of the ovulation inducing hormone complex (probably primarily LH) is, however, inhibited by such a dose of progesterone, and probably accounts for the inhibition of ovulation. The findings also suggest that the amount of progesterone secreted by the functioning corpora lutea during pseudopregnancy in the rat is equivalent in effect to between 2 and 5 mg of progesterone injected once daily.

Involvement of the adrenal gland in the suckling-induced decrease in LH and FSH secretion and the concomitant increase in prolactin secretion in the rat

1990 ◽  
Vol 125 (2) ◽  
pp. 279-285 ◽  
Author(s):  
K. Taya ◽  
S. Sasamoto
Keyword(s):  
Adrenal Gland ◽  
Ovarian Function ◽  
Plasma Concentrations ◽  
Prolactin Secretion ◽  
Plasma Prolactin ◽  
Luteal Function ◽  
Follicular Maturation ◽  
High Concentrations ◽  
Ovulatory Follicles

ABSTRACT The role of the adrenal gland in the regulation of gonadotrophin and prolactin secretion in the lactating rat was investigated. Changes in secretion of LH, FSH, prolactin, ACTH, β-lipotrophin (β-LPH), inhibin, corticosterone and progesterone after adrenalectomy were examined during the second half of lactation. Follicular maturation was determined by the ability of the follicles to ovulate in response to 10IU human chorionic gonadotrophin (hCG). Adrenalectomy on day 10 of lactation prevented an increase in plasma concentrations of LH and FSH in response to ovariectomy performed at the same time as adrenalectomy, and markedly stimulated secretion of ACTH, β-LPH and prolactin. Adrenalectomy reduced the number of follicles capable of ovulating in response to hCG. Concentrations of inhibin and progesterone in the plasma significantly decreased after adrenalectomy, indicating that development of ovulatory follicles and luteal function had been suppressed. Abolishing the increase in plasma concentrations of LH and inducing a decrease in FSH in the plasma by adrenalectomy therefore prevented maturation of a new set of follicles usually seen during the second half of lactation in rats. The decrease in plasma concentrations of LH also inhibited the ability of the corpus luteum to secrete progesterone, although high concentrations of plasma prolactin were maintained in adrenalectomized lactating rats. These results indicate that the pituitary-adrenal system is capable of influencing the maintenance of a normal secretion of gonadotrophin and prolactin as well as the maintenance of ovarian function during lactation in the rat. Journal of Endocrinology (1990) 125, 279—285

LEVELS OF α-MELANOTROPHIN IN THE PLASMA AND PITUITARY GLANDS OF FETAL AND JUVENILE RATS, AND IN THE PLASMA OF ADULT FEMALE RATS DURING PREGNANCY AND LACTATION

1980 ◽  
Vol 84 (3) ◽  
pp. 363-370 ◽  
Author(s):  
J. F. WILSON ◽  
MERRILL A. MORGAN
Keyword(s):  
Plasma Concentrations ◽  
Postnatal Period ◽  
Female Rats ◽  
Pregnant Rats ◽  
Juvenile Rats ◽  
Stress Effects ◽  
Fetal Rats ◽  
Pregnancy And Lactation ◽  
Pituitary Glands ◽  
Reproductive Processes

α-Melanotrophin was detected by radioimmunoassay in the pituitary glands of fetal rats from day 17 of gestation. The pituitary content of α-melanotrophin increased regularly, at a gradually decreasing rate, throughout gestation and in the postnatal period. Concentrations of α-melanotrophin in the plasma of fetal and newborn rats were below the detection limit of the radioimmunoassay (10 pmol/l). Detectable concentrations were first found in young rats on day 3 after birth and did not differ significantly from those in their mothers throughout the period of suckling. Plasma concentrations of α-melanotrophin were raised in pregnant rats during the last 4 days of gestation and after parturition. They returned to basal levels in the 2 weeks after delivery. After weaning at 3 weeks of age, a large increase in the plasma concentration of α-melanotrophin was detected in juvenile rats. Plasma levels had returned to the normal adult range by 6 weeks of age. The increases in α-melanotrophin in the blood were thought to be the result of non-specific stress effects. The data did not provide evidence for a role for α-melanotrophin in reproductive processes in the rat.

2-Hydroxyoestradiol acutely inhibits prolactin secretion from the superfused pituitary glands of normal female rats: evidence for a cyclical effect

1986 ◽  
Vol 111 (2) ◽  
pp. 199-204 ◽  
Author(s):  
P. K. Banks ◽  
S. E. Inkster ◽  
N. White ◽  
S. L. Jeffcoate
Keyword(s):  
Suppressive Effect ◽  
Prolactin Secretion ◽  
Female Rats ◽  
Normal Female ◽  
Female Rat ◽  
Naturally Occurring ◽  
Before And After ◽  
Pituitary Glands ◽  
Layer Chromatography

ABSTRACT Catecholoestrogens are naturally occurring metabolites of oestrogens which are found in brain tissue and for which a neuroendocrine role has been postulated. However, reports of their effects on prolactin secretion are ambiguous and as yet no defined function has been attributed to them. The effects of 2-hydroxyoestradiol (2-OHE2) and dopamine on the release of prolactin in vitro by perfused pituitary glands from normal adult female rats at different stages of the oestrous cycle have been investigated. The purity and stability of the 2-OHE2 preparation before and after exposure to pituitary tissue was confirmed by radioenzymatic assay and subsequent thin-layer chromatography. Dopamine (500 nmol/l, 100 nmol/l) was found consistently to suppress release by 60%; this effect was immediate and reversible upon removal of the dopamine. In contrast, the effects of 2-OHE2 (10 nmol/l, 100 nmol/l) were found to vary during the cycle. No effect on prolactin release was evident during either dioestrus or pro-oestrus, but during oestrus a similar, though less potent, suppression of prolactin secretion to that of dopamine was observed (35% suppression compared with controls). The cyclical variation in the suppressive effect of 2-OHE2 on prolactin secretion in the female rat is compatible with a postulated neuroendocrine role for this catecholoestrogen. J. Endocr. (1986) 111, 199–204

Differential effect of difluoromethylornithine on the increases in plasma concentrations of reproductive hormones on the afternoon of pro-oestrus in the rat

1989 ◽  
Vol 121 (3) ◽  
pp. 495-499 ◽  
Author(s):  
S. A. Nicholson ◽  
G. A. Wynne-Jones
Keyword(s):  
Differential Effect ◽  
Time Course ◽  
Plasma Concentrations ◽  
Specific Inhibitor ◽  
Inhibitory Effect ◽  
Prolactin Secretion ◽  
Reproductive Hormones ◽  
Female Rats ◽  
Limited Time ◽  
The Times

ABSTRACT In our colony of female rats (220–320 g body weight) undergoing regular 4-day oestrous cycles there were significant, marked rises in concentrations of LH, FSH and prolactin between 09.00 and 19.00 h on pro-oestrus. The i.p. injection of difluoromethylornithine (DFMO; 40–400 mg/kg), a specific inhibitor of the activity of ornithine decarboxylase, at 15.00 h on prooestrus had a differential effect on the rise in plasma concentrations of the various hormones thereafter. The drug produced a significant, partial, dose-related suppression of the rise in plasma concentrations of LH and prolactin, but had no significant effect on the rise in FSH. For time-course studies, 120 mg DFMO/kg were injected at 13.00, 15.00 or 17.00 h and groups of animals killed at 19.00 h. Only the injection at 15.00 h was effective in causing a significant reduction in plasma concentrations of LH and prolactin at 19.00 h. Pituitary content of the hormones was found to be unaffected by the administration of DFMO at the times and doses tested. These results suggest that DFMO has a selective inhibitory effect on enhanced LH and prolactin secretion on the afternoon of pro-oestrus in the rat, whilst not affecting FSH release. There seems to be a limited time (after 13.00 but before 17.00 h) during which its administration is effective. Journal of Endocrinology (1989) 121, 495–499

Isolation, characterization and radioimmunoassay of luteinizing hormone in the brushtail possum

1997 ◽  
Vol 9 (4) ◽  
pp. 419 ◽  
Author(s):  
L. G. Moore ◽  
W. Ng Chie ◽  
S. Lun, S. B. Lawrence ◽  
D. A. Heath ◽  
K. P. McNatty
Keyword(s):  
Amino Acid ◽  
Luteinizing Hormone ◽  
Plasma Concentrations ◽  
Gel Filtration ◽  
Hydrophobic Interaction Chromatography ◽  
Cross Reactivity ◽  
Brushtail Possum ◽  
Corpora Lutea ◽  
Rate Of Increase ◽  
Pituitary Glands

Luteinizing hormone (LH) was purified from brushtail possum (Trichosurus vulpecula) pituitary glands. The purification procedure consisted of ammonium sulfate precipitation followed by triazinyl-dye chromatography, hydrophobic interaction chromatography and gel filtration. A yield of 10 µg LH g-1 pituitary with a recovery of 20% was obtained from 1400 pituitary glands (20·3 g). Contamination with possum follicle-stimulating hormone (FSH) was ≤0.05%. The amino acid analysis and the N-terminal sequencing for 10 cycles revealed close homology with LH from other mammals. Minor amounts of LH that had been truncated near the N-terminal were also detected. No contaminating proteins were found by amino acid sequencing. The potency of possum LH was 20% that of ovine LH in a receptor assay using possum testicular receptors and 4% that of ovine LH when bovine corpora lutea receptors were used. Possum LH was able to stimulate production of cyclic adenosine 3′ ,5′-monophosphate by bovine granulosa cells. A radioimmunoassay (RIA) for possum LH using 125I-possum LH and an antiserum raised against ovine LH was developed. The RIA has a sensitivity of 0·15 ng mL-1 , a 50% displacement of 1·9 ng mL-1 and a cross-reactivity of <0 · 02% against possum FSH. Plasma concentrations were 0·24 ± 0· 04 ng mL-1 (n = 8) and 0·39 ± 0·12 ng mL-1 (n = 8) in female and male possums respectively. Administration of mammalian gonadotrophin-releasing hormone (GnRH) and chicken GnRH II stimulated increases in plasma LH concentrations in male and female possums. When comparing LH responses with administration of mammalian GnRH or chicken GnRH II, plasma LH concentrations remained elevated for a longer period of time in males than in females (P < 0· 01); plasma LH concentrations also remained elevated for longer after mammalian GnRH than after chicken GnRH II (P < 0· 01). Gonadectomy stimulated an increase in plasma concentrations of LH in both male (P < 0· 01) and female (P < 0· 05) possums. The rate of increase in plasma LH concentrations in males was faster than that in females. In summary, we have purified, partially characterized, and developed a RIA for possum LH.

Reduction of 5-day cycle length of female rats by treatment with bromocriptine

1983 ◽  
Vol 97 (1) ◽  
pp. 83-89 ◽  
Author(s):  
P. van der Schoot ◽  
J. Th. J. Uilenbroek
Keyword(s):  
Cycle Length ◽  
Female Rats ◽  
Corpora Lutea ◽  
Normal Numbers ◽  
Ovarian Weight ◽  
Follicular Maturation ◽  
Large Numbers ◽  
Luteal Tissue ◽  
Pattern Characteristic ◽  
High Concentrations

Rats with 5-day ovarian cycles were injected daily with 1 mg bromocriptine. This treatment resulted in a change of cycle length from 5 to 4 days and a rapid increase in ovarian weight. The increase in ovarian weight resulted from the accumulation of large numbers of corpora lutea. Normal numbers of corpora lutea were formed during each cycle but luteal bodies did not disappear subsequently. Luteolysis affected only minor foci of luteal tissue and the majority of luteal tissue remained histologically intact throughout the further period of study. The reduction of cycle length from 5 to 4 days occurred when bromocriptine was administered from the day of ovulation only. If treatment was commenced at a later time during the cycle it was not effective. Treatment with bromocriptine appeared to affect the concentrations of progesterone in the blood during dioestrus. During treatment the rats showed the pattern characteristic for 4-day cycles: typically, the high concentrations of progesterone on the day after metoestrus remained absent. These data suggest (1) that the latter part of the production of progesterone during dioestrus by 'non-functional corpora lutea' is dependent on prolactin and (2) that prolongation of high progesterone production after metoestrus plays an important role in changing the length of the cycle from 4 to 5 days. Treatment with bromocriptine did not significantly affect the rate of maturation of follicles destined for the next ovulation. It is possible that follicular maturation is not among the critical variables which determine whether normal ovulatory cycles will last for 4 or 5 days.

Observations on the effects of prolactin on LH-receptors and steroidogenesis in corpus luteum and testis of the hypophysectomized rat

1982 ◽  
Vol 99 (3) ◽  
pp. 437-442 ◽  
Author(s):  
R. J. C. van Straalen ◽  
G. H. Zeilmaker
Keyword(s):  
Pituitary Gland ◽  
Corpus Luteum ◽  
Binding Sites ◽  
Female Rats ◽  
Male Rats ◽  
Rapid Decline ◽  
Corpora Lutea ◽  
Serum Progesterone ◽  
Male And Female Rats ◽  
Hypophysectomized Rats

Abstract. In this study the effects of hypophysectomy and autotransplantation of the pituitary gland on the concentration of hCG-binding sites (LH-receptors) and steroidogenesis in the corpus luteum and the testis of the rat were investigated. It was found that during pseudopregnancy both hCG-binding to homogenates of isolated corpora lutea and the progesterone levels in blood increase until day 7 and subsequently decrease until day 13. Hypophysectomy on day 5 led to a decrease of the number of LH-receptors and the serum progesterone level. By contrast hypophysectomy followed by autotransplantation of the pituitary gland increased the LH-receptor concentration and progesterone synthesis in spite of non-detectable LH-levels. Progesterone implants in hypophysectomized rats did not influence the number of LH-receptors. Hypophysectomy on day 0 without pituitary gland transplantation did not prevent the formation of some luteal LH-receptors measured on day 5 although progesterone was not secreted. A similar effect of prolactin secreted by pituitary autografts on LH-receptors was seen in the testis. The rapid decline of the number of binding sites normally observed after hypophysectomy was prevented by the presence of two pituitary autografts. Testosterone and LH-levels were non-detectable in the operated male rats. These data show that progesterone secretion by the corpora lutea is always associated with the presence of LH-receptors, regardless whether serum LH-levels are detectable or not. Moreover it appears that prolactin maintains or even increases the amount of LH-receptors in hypophysectomized male and female rats.

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