Luteolytic Effect of Prostaglandin in the Guinea-pig

Blatchley, F. R.; Donovan, B. T.

doi:10.1038/2211065a0

Cited by 132 publications

(28 citation statements)

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“…provoked rapid (10 sec) and sustained (up to 60 min) increases in the levels of inositol mono-, bis-, and trisphosphates (InsP, InsP2, and InsP3, respectively PGF2a-induced increases in [Ca2+], were also independent of extracellular calcium. These findings demonstrate that the action of PGF2a is coupled to the phospholipase C-InsP3 and diacylglycerol second messenger system in the corpus luteum.The ability of prostaglandin F2a (PGF2a) to cause a loss of function of the corpus luteum was demonstrated over 15 years ago (1,2), but the precise mechanism of action of PGF2, remains unknown. PGF2a-induced luteolysis is correlated with changes in luteal membrane lipid composition and reductions of membrane fluidity (3-6), which have been suggested to prevent gonadotropin receptor aggregation (7) and the association and coupling to adenylate cyclase (8-10).…”

mentioning

confidence: 99%

Prostaglandin F2 alpha stimulates phosphatidylinositol 4,5-bisphosphate hydrolysis and mobilizes intracellular Ca2+ in bovine luteal cells.

Davis¹,

Weakland²,

Weiland³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

161

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The present studies were conducted to determine whether prostaglandin F2a (PGF2a) stimulates the production of "second messengers" derived from inositol phospholipid hydrolysis and increases intracellular free Ca2+ ([Ca2+],) in isolated bovine luteal cells. PGF2. provoked rapid (10 sec) and sustained (up to 60 min) increases in the levels of inositol mono-, bis-, and trisphosphates (InsP, InsP2, and InsP3, respectively PGF2a-induced increases in [Ca2+], were also independent of extracellular calcium. These findings demonstrate that the action of PGF2a is coupled to the phospholipase C-InsP3 and diacylglycerol second messenger system in the corpus luteum.The ability of prostaglandin F2a (PGF2a) to cause a loss of function of the corpus luteum was demonstrated over 15 years ago (1,2), but the precise mechanism of action of PGF2, remains unknown. PGF2a-induced luteolysis is correlated with changes in luteal membrane lipid composition and reductions of membrane fluidity (3-6), which have been suggested to prevent gonadotropin receptor aggregation (7) and the association and coupling to adenylate cyclase (8-10). PGF2a also acts at postreceptor sites to inhibit steroidogenesis (10, 11). Behrman and coworkers (12,13)

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mentioning

confidence: 99%

Prostaglandin F2 alpha stimulates phosphatidylinositol 4,5-bisphosphate hydrolysis and mobilizes intracellular Ca2+ in bovine luteal cells.

Davis¹,

Weakland²,

Weiland³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

161

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confidence: 99%

The effect of continuous treatment with prostaglandin F-2 on oestrous cycle length and corpus luteum regression in hysterectomized guinea-pigs

Tso¹,

Tam²

1977

Reproduction

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It has been established that prostaglandin (PG) F-2\g=a\induces the involution of corpora lutea (CL) in hysterectomized guinea-pigs (Blatchley & Donovan, 1969) and that the guinea-pig uterus is probably the major source of this luteolytic factor (Poyser, 1972). However, the measurement of PGF-2\g=a\levels in the utero-ovarian venous plasma of cyclic guinea-pigs (Blatchley, Donovan, Horton & Poyser, 1972) revealed that, even though the concentration was low, PGF-2\g=a\was present throughout the oestrous cycle and that there was asynchrony in luteal regression (Days 12\p=n-\16: Rowlands, 1956) and the peak of PGF-2\g=a\secretion (Day 15: Blatchley et al., 1972). During experiments to study the effects ofPGF-2\g=a\on the different tissue components of the ovary, it was found that the CL responded to the luteolytic action of PGF-2\g=a\only at certain times.Guinea-pigs were hysterectomized before puberty (24-32 days old) and then injected i.p. twice every day with 0-125 mg PGF-2a (equivalent to 0-168 mg THAM salt, Upjohn Co.) in 0-5 ml 0-9% NaCl, i.e. 0-057-0-100 mg PGF-2a/100 g body weight/day (Group A). Other guinea-pigs of the same age were (i) hysterectomized and injected twice daily with 0-5 ml NaCl (Group B), (ii) subjected to sham-operation, i.e. sectioning of the utero-vaginal junction but leaving the uterine horns in situ, and similarly treated with NaCl (Group C), and (iii) given no treatment (Group D). Most animals were killed in the second oestrous cycle, but 3 Group-and 3 Group-D animals were maintained until the early stages of the fourth cycle. At autopsy the ovaries were fixed and serially sectioned for histological observation. The CL volume was calculated from the mean of 3 diameters set at right angles to one another, measured with an ocular micrometer from the ovarian sections. Oestrous cycle length was calculated by daily examination of the vaginal closure membrane and the day after the first day the vaginal membrane was fully perforate was taken to be Day 1 of the cycle.The first vaginal opening was observed in animals of Groups C and D when they were 36-2 ± 0-8 (N = 23) days old (mean ± S.E.M., the total of 11 animals in Group C and 12 animals in Group D), but the first vaginal opening occurred at 45-2 ± 2-9 (N = 14) days of age in the PGF-2a-treated animals in Group A. It is not clear whether this delay was due to the combined effect of hysterectomy and PGF-2a treatment or just the shock of hysterectomy as the amount of blood loss in hysterectomy was always greater than in the sham-operation. However, once the first oestrus had occurred the cycle lengths in Group A were, for the first to third cycle, 14-9 ± 0-6 (number of cycles observed = 12), 15-0 ±1-2 (3) and 16-3 ± 0-9 (3) days, respectively; and these durations were not significantly differ¬ ent (Student's / test) from those of the control animals in Group D (15-4 ± 0-6 (9), 16-3 ± 0-3 (3) and 15-7 ± 0-3 (3) days, respectively). There was also no significant difference between the duration of the first cycle in Groups C and D. Continual t...

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“…If these were involved then the decreased prostaglandin levels in the indomethacin-influenced uterus could be an important factor. In this regard it has been found that the intraluminal release of indomethacin in the guinea-pig caused a pronounced elongation of the oestrous cycle, (Horton & Poyser, 1973) and in this species uterine prostaglandin F2e was markedly luteolytic (Blatchley & Donovan, 1969). The measurements of incorporation of radioactive leucine in the uterine horns show a decrease in protein synthesis in the horn with an indomethacin implant.…”

Section: Discussionmentioning

confidence: 93%

Impairment of protein synthesis in the rat uterus following intrauterine delivery of indomethacin

Hurst

Peplow

1986

British J Pharmacology

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1 When indomethacin was incorporated into a slow-release preparation (initial content 1.6 mg drug) and placed in one horn of the rat uterus, a significant decrease in protein synthesis occurred for this horn in comparison with control animals (as determined by the incorporation of radioactive leucine) at three different times after insertion. Decreases of 20, 21% at the two times of dioestrus and 28% at the time of oestrus selected were determined. No significant reduction in protein synthesis was found for the contralateral horn, although there was a tendency for it to be lowered at the earliest time of examination when two complete oestrous cycles had passed following insertion. 2 Measurement of the uptake of radioactive leucine by the uterine horns showed no change in response to indomethacin delivery compared to the control animals with silastic implants, and suggested that the transport system for this amino acid in cells of the uterine horns was not affected by the drug. 3 It was apparent that in instances when the protein synthesis of the uterine horn was impaired by indomethacin that a decrease in RNA/DNA ratio existed. At the latest time examined, no alteration in DNA content occurred in the indomethacin-influenced horn but there was a significant reduction in RNA content. 4 For a small proportion of the animals with indomethacin-releasing preparations there was a tendency to show a lengthening of the oestrous cycle over the first three cycles following insertion. Whether this was due to a direct effect of indomethacin on the ovaries or an effect caused by decreased concentrations of prostaglandins in the uterus was unknown. 5 These results provide further evidence that non-steroidal anti-inflammatory drugs can interfere with the synthesis of macromolecular substances, and that such changes need to be taken into account when considering the overall effect of these drugs on tissues and organs.

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Luteolytic Effect of Prostaglandin in the Guinea-pig

Cited by 132 publications

References 4 publications

Prostaglandin F2 alpha stimulates phosphatidylinositol 4,5-bisphosphate hydrolysis and mobilizes intracellular Ca2+ in bovine luteal cells.

Prostaglandin F2 alpha stimulates phosphatidylinositol 4,5-bisphosphate hydrolysis and mobilizes intracellular Ca2+ in bovine luteal cells.

The effect of continuous treatment with prostaglandin F-2 on oestrous cycle length and corpus luteum regression in hysterectomized guinea-pigs

Impairment of protein synthesis in the rat uterus following intrauterine delivery of indomethacin

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