scholarly journals Prostaglandin F2α (PGF2α) and Prolactin Signaling: PGF2α-Mediated Inhibition of Prolactin Receptor Expression in the Corpus Luteum

Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3301-3305 ◽  
Author(s):  
Carlos Stocco ◽  
Jean Djiane ◽  
Geula Gibori
Keyword(s):  
Corpus Luteum ◽  
Time Course ◽  
Prolactin Receptor ◽  
Prostaglandin F2α ◽  
Receptor Expression ◽  
Luteal Cell ◽  
Pregnant Rats ◽  
Prolactin Signaling ◽  
Stimulation Of

Abstract It is well established that prolactin (PRL) sustains, whereas prostaglandin F2α (PGF2α) curtails, progesterone production by the rodent corpus luteum (CL). We have previously shown that PGF2α inhibits the expression of several luteal genes stimulated by PRL, whereas it stimulates other genes inhibited by this hormone. We have also found that PGF2α stimulation of 20α-hydroxysteroid dehydrogenase (20αHSD), an enzyme that catabolizes progesterone, at the end of pregnancy is accompanied by a dramatic decrease in PRL receptor (PRL-R) expression. These findings, and the fact that the factors that inhibit PRL-R are not known, led us to examine in vivo whether the decline in PRL-R at the end of pregnancy is due to PGF2α and to also find out whether PGF2α opposes PRL action by inhibiting PRL-R expression. Using the PGF2α receptor (PGF2α-R) knockout, we examined whether the absence of the PGF2α-R prevents the decline in the expression of both the short and long forms of the PRL-R in the CL. We found that, in sharp contrast to the wild-type mice, in which both forms of the PRL-R decline to low levels between d 18–20 of pregnancy, expression of these receptors remained elevated in the PGF2α-R null mice. Furthermore, administration of PGF2α to pregnant rats inhibited PRL-R expression. Time-course analysis revealed that PGF2α treatment decreases both isoforms of PRL-R within 1 h of treatment in vivo, whereas its stimulatory effect on 20αHSD expression was further delayed. Similar results were obtained with luteinized granulosa cells in culture. To examine whether the decline in PRL-R is involved/necessary for PGF2α action, cells were transfected with a constitutively active PRL-R. The expression of this receptor did not prevent PGF2α effect on PRL-R or 20αHSD expression. Taken together, these results demonstrate that PGF2α inhibits the expression of the PRL-R and that the decline in both forms of the PRL-R that occurs at the end of pregnancy in the CL is due to PGF2α. The results further suggest that PGF2α-mediated stimulation of 20αHSD is independent from PGF2α inhibition of PRL signaling in luteal cell.

scholarly journals In Vivo and in Vitro Inhibition of cyp19 Gene Expression by Prostaglandin F2α in Murine Luteal Cells: Implication of GATA-4

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 4957-4966 ◽  
Author(s):  
Carlos Stocco
Keyword(s):  
Time Course ◽  
Cell Function ◽  
Prostaglandin F2α ◽  
Luteal Cell ◽  
Mrna Levels ◽  
Luteal Cells ◽  
Cyp19 Gene ◽  
17Β Estradiol

Abstract A major function of the corpus luteum (CL) is to secrete progesterone. In rats, this gland also produces significant amounts of 17β-estradiol. Progesterone and 17β-estradiol are important regulators of rat luteal cell function. Estrogen biosynthesis is catalyzed by P450aromatase (P450arom), which is encoded by the cyp19 gene. In the rat CL, P450arom is expressed throughout pregnancy until the day before parturition, when it rapidly decreases. The mechanisms that control P450arom expression in luteal cells, particularly, the one or more factors that cause its rapid fall before parturition, are not known. Inasmuch as prostaglandin (PG) F2α plays a key role in the regulation of luteal function at the end of pregnancy, the purpose of this investigation was to determine whether PGF2α affect the expression of P450arom in the CL before parturition. PGF2α decreased luteal P450arom mRNA and protein levels in vivo and in vitro. A decrease in P450arom mRNA was also observed in mice CL just before parturition, but this change did not take place in PGF2α receptor knockout mice. The time course of the decrease in P450arom mRNA by PGF2α reflected the P450arom mRNA half-life determined by actinomycin D. Moreover, nuclear run-on assay showed that PGF2α attenuates P450arom gene transcription. Gel shift assays revealed that GATA-4 binds to the P450aromatase promoter, and that such binding is increased by PGF2α. It is concluded that PGF2α decreases luteal P450arom mRNA levels at the end of pregnancy in rodents by inhibiting cyp19 expression.

scholarly journals Prostaglandin F2α Represses IGF-I-Stimulated IRS1/Phosphatidylinositol-3-Kinase/AKT Signaling in the Corpus Luteum: Role of ERK and P70 Ribosomal S6 Kinase

2010 ◽  
Vol 24 (3) ◽  
pp. 632-643 ◽  
Author(s):  
Edward Arvisais ◽  
Xiaoying Hou ◽  
Todd A. Wyatt ◽  
Koumei Shirasuna ◽  
Heinrich Bollwein ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Prostaglandin F2α ◽  
Serine Phosphorylation ◽  
Phosphatidylinositol 3 Kinase ◽  
Akt Activation ◽  
Diminished Capacity ◽  
Igf I ◽  
In Vitro Treatment

Abstract Little is known about the early intracellular events that contribute to corpus luteum regression. Experiments were designed to determine the effects of prostaglandin F2α (PGF2α) on phosphatidylinositol-3-kinase (PI3K)/Akt signaling in the corpus luteum in vivo and in vitro. Treatment of midluteal-phase cows with a luteolytic dose of PGF2α resulted in a rapid increase in ERK and mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K1) signaling and a rapid suppression of Akt phosphorylation in luteal tissue. In vitro treatment of primary cultures of luteal cells with PGF2α also resulted in an increase in ERK and mTOR/p70S6K1 signaling and a diminished capacity of IGF-I to stimulate PI3K, Akt, and protein kinase C ζ activation. Accounting for the reductions in PI3K and Akt activation observed in response to PGF2α treatment, we found that PGF2α promoted the phosphorylation of serine residues (307, 612, 636) in the insulin receptor substrate 1 (IRS1) peptide sequence in vivo and in vitro. Serine phosphorylation of IRS1 was associated with reduced formation of IGF-I-stimulated IRS1/PI3Kp85 complexes. Furthermore, treatment with inhibitors of the MAPK kinase 1/ERK or mTOR/p70S6K1 signaling pathways prevented PGF2α-induced serine phosphorylation of IRS1 and abrogated the inhibitory actions of PGF2α on Akt activation. Taken together, these experiments provide compelling evidence that PGF2α treatment stimulates IRS1 serine phosphorylation, which may contribute to a diminished capacity to respond to IGF-I. It seems likely that the rapid changes in phosphorylation events are among the early events that mediate PGF2α-induced corpus luteum regression.

In vivo study on medullary H(+)-sensitive neurons

1990 ◽  
Vol 69 (4) ◽  
pp. 1408-1412 ◽  
Author(s):  
N. Kogo ◽  
H. Arita
Keyword(s):  
Time Course ◽  
Direct Application ◽  
Ventrolateral Medulla ◽  
Similar Time ◽  
Central Chemoreceptors ◽  
Ph Dependent ◽  
Spontaneously Breathing ◽  
Medullary Neurons ◽  
Stimulation Of

Using the micro pressure ejection technique, we examined responses of medullary neurons with nonphasic discharges (164 units) to direct application of acidified mock cerebrospinal fluid (CSF, pH 6.85-7.05) in decerebrated spontaneously breathing cats. We found 16 H(+)-sensitive cells; they were excited promptly on application of approximately 500 pl of acidified mock CSF in the vicinity of the neuron under investigation, whereas they were unaffected by microejection of the control mock CSF (pH 7.25-7.60). Of the 16 H(+)-sensitive cells, 10 units were further found to be excited by transcapillary stimulation of the central chemoreceptors by using a method of intravertebral arterial injection of CO2-saturated saline. The discharges increased in a similar time course to that of ventilatory augmentation. Distributions of these 10 specific H(+)-sensitive cells were found in the vicinity of nucleus tractus solitarii as well as deep in the ventrolateral medulla. The present results suggest a possibility that pH-dependent central chemoreceptors, if any, would be located in two distinct medullary regions described in this study.

scholarly journals Characterization of Prejunctional Muscarinic Receptors: Effects on the Release of VIP and Functional Responses and Receptor Expression in the Ovine Submandibular Gland

2009 ◽  
Vol 2009 ◽  
pp. 1-6
Author(s):  
Anders T. Ryberg ◽  
Ondrej Soukup ◽  
Gunnar Tobin
Keyword(s):  
Electrical Stimulation ◽  
Submandibular Gland ◽  
Muscarinic Receptor ◽  
Muscarinic Receptors ◽  
Receptor Expression ◽  
Receptor Subtypes ◽  
Chorda Tympani Nerve ◽  
Functional Responses ◽  
Stimulation Of

In the in vivo experiments on anaesthetized sheep, it was presently examined whether muscarinic receptor antagonists with diverse selectivity affect the release of VIP in response to electrical stimulation of the parasympathetic chorda tympanic nerve differently, and if the changes in the release could be associated to altered secretory and vasodilator responses. The location of the muscarinic receptor subtypes was examined also. In the experiments, blood was collected out of the submandibular venous drainage before and during electrical stimulation of chorda tympani nerve in the absence and presence either of pirenzepine or methoctramine. While metchoctramine increased the output of protein, pirenzepine inhibited flow of saliva and increased protein output, vasodilatation, and VIP output. In morphological examinations, the inhibitory muscarinic M4 receptor occurred interacinarily in the gland. It is concluded that prejunctional muscarinic receptors, most likely of the M4 subtype, exert inhibitory modulation of the parasympathetic release of VIP in the ovine submandibular gland.

scholarly journals Changes in the sensitivity to glucagon of lipolysis in adipocytes from pregnant and lactating rats

1988 ◽  
Vol 254 (3) ◽  
pp. 661-665 ◽  
Author(s):  
V A Zammit
Keyword(s):  
Adipose Tissue ◽  
The Other ◽  
High Concentration ◽  
Response Curves ◽  
Pregnant Rats ◽  
Adipose Tissue Lipolysis ◽  
The Right ◽  
Peak Lactation ◽  
Stimulation Of

1. Rates of lipolysis were measured at different concentrations of glucagon in adipocytes prepared from parametrial adipose tissue of fed or starved rats in different reproductive states. All experiments were performed in the presence of a high concentration of adenosine deaminase (1 unit/ml). 2. Maximal rates of lipolysis (elicited by 25 nM-glucagon in each instance) were higher in adipocytes from peak-lactating rats than those from pregnant animals in both the fed and starved states. 3. Of adipocytes from fed animals, those from peak-lactating rats were the most sensitive to glucagon, whereas those from late-pregnant and early-lactating rats were 1-2 orders of magnitude less sensitive. 4. Adipocytes from 24 h-starved rats showed a much smaller stimulation of lipolysis by glucagon, making the assessment of sensitivity difficult. Therefore, rates of lipolysis were also measured in the presence of a maximally anti-lipolytic dose of insulin. The presence of insulin did not alter the relative sensitivities to glucagon of adipocytes from fed animals in different reproductive states, although all dose-response curves were shifted to the right. When lipolysis in adipocytes from starved animals was measured in the presence of insulin, it became evident that starvation for 24 h markedly increased the sensitivity of adipocytes from late-pregnant rats to glucagon, but did not affect that of cells from animals in the other reproductive states. 5. It is concluded that the large changes in sensitivity to glucagon that occurred during the reproductive cycle may enable the modulation of adipose-tissue lipolysis in vivo to satisfy the different metabolic requirements of the animal in the transition from pregnancy to peak lactation.

261. Resistance to GH signalling through stat5 is an early event in PGF2α induced luteolysis in the ewe

2005 ◽  
Vol 17 (9) ◽  
pp. 106
Author(s):  
S. T. Anderson ◽  
D. H. L. Kusters ◽  
J. L. Barclay ◽  
J. D. Curlewis
Keyword(s):  
Western Blot ◽  
Corpus Luteum ◽  
Intramuscular Injection ◽  
Jugular Vein ◽  
Prolactin Receptor ◽  
Early Event ◽  
Control Groups ◽  
Pregnant Rats ◽  
Gh Receptor ◽  
Receptor Signalling

Recently we have shown that prostaglandin-induced luteolysis in pregnant rats involves resistance to prolactin-receptor signalling through the JAK2/STAT5 pathway.1 In the present study, we investigate whether PGF2alpha acts similarly to inhibit GH signalling in the ovine corpus luteum. The oestrous cycle of ewes was synchronised using cloprostenol and CIDR-G devices with oestrus detected by testosterone treated wethers with raddles. Twelve days after the first recorded oestrous mark, ewes were given an intramuscular injection of either saline or cloprostenol (125 µg), followed 1 h later with an intravenous injection (jugular vein) of either vehicle or 1.5 mg recombinant bovine GH (rbGH, Monsanto). After a further 15 min ewes were killed by pentobarbitone overdose and the corpus luteum removed. Tyrosine phosphorylation of STAT5 (STAT-P) in the corpus luteum was determined by immunoprecipitation and Western blot (n = 4 ewes/treatment). STAT5-P levels were relatively low in all ewes that were not treated with rbGH. Treatment with rbGH significantly (P < 0.01) increased STAT5-P in the corpus luteum of ewes pretreated with saline, compared to both control groups. However the STAT5-P response to rbGH was significantly (P < 0.01) reduced by the pretreatment with cloprostenol, although the response remained significantly (P < 0.05) higher than both control groups. In summary we have shown that (1) as expected, the GH-receptor signals through STAT5 in the ovine corpus luteum and (2) cloprostenol induces resistance to this GH-receptor signalling pathway. (1)Curlewis et al. (2002). Endocrinology 143, 3984–3993.

Cis- andtrans-acting factors regulating transcription of the BGT1 gene in response to hypertonicity

1998 ◽  
Vol 274 (4) ◽  
pp. F753-F761 ◽  
Author(s):  
Hiroshi Miyakawa ◽  
Seung Kyoon Woo ◽  
Ching-Pu Chen ◽  
Stephen C. Dahl ◽  
Joseph S. Handler ◽  
...  
Keyword(s):  
Dna Binding ◽  
Time Course ◽  
Mutational Analysis ◽  
Consensus Sequence ◽  
Dimethyl Sulfate ◽  
Base Pairs ◽  
Biochemical Basis ◽  
Activation Of Transcription ◽  
Stimulation Of

We have previously identified a tonicity-responsive enhancer (TonE) in the promoter region of the canine BGT1 gene. TonE mediates hypertonicity-induced stimulation of transcription. Here, we characterize TonE and TonE binding proteins (TonEBPs) to provide a biochemical basis for cloning of the TonEBPs. Mutational analysis applied to both hypertonicity-induced stimulation of transcription and TonEBP binding reveals that TonE is 11 base pairs in length, with the consensus sequence of (C/T)GGAAnnn(C/T)n(C/T). Activity of the TonEBPs increases in response to hypertonicity with a time course similar to that of transcription of the BGT1 gene. Studies with inhibitors indicate that translation, but not transcription, is required for activation of the TonEBPs. Phosphorylation is required for the stimulation of transcription but not for activation of DNA binding by the TonEBPs. In vivo methylation by dimethyl sulfate reveals that the TonE site of the BGT1 gene is protected with a time course like that of activity of the TonEBPs and activation of transcription. Ultraviolet cross-linking indicates that the TonEBPs share a DNA binding subunit of 200 kDa.

scholarly journals Transforming ras proteins accelerate hormone-induced maturation and stimulate cyclic AMP phosphodiesterase in Xenopus oocytes.

1990 ◽  
Vol 10 (4) ◽  
pp. 1689-1696 ◽  
Author(s):  
S E Sadler ◽  
J L Maller ◽  
J B Gibbs
Keyword(s):  
Enzyme Activity ◽  
Time Course ◽  
Xenopus Oocytes ◽  
Insulin Treatment ◽  
Ras Oncogene ◽  
Ras Proteins ◽  
Phosphodiesterase Activity ◽  
Oncogene Products ◽  
Stimulation Of

Transforming Harvey (Ha) ras oncogene products accelerated the time course of Xenopus oocyte maturation induced by insulin, insulinlike growth factor 1, or progesterone. The transforming constructs, [Val-12]Ha p21 and [Val-12, Thr-59]Ha p21, displayed equal potency and efficacy in their abilities to accelerate the growth peptide-induced response. Normal Ha p21 was only 60% as powerful and one-fifth as potent as the mutants containing valine in the 12 position. In contrast, two nontransforming constructs, [Val-12, Ala-35, Leu-36, Thr-59]Ha p21 and [Val-12, Thr-59]Ha(term-174) p21, had no effect on the time course of hormone-induced maturation. Effects of the transforming ras proteins on hormone-induced maturation correlated with their abilities to stimulate in vivo phosphodiesterase activity measured after microinjection of 200 microM cyclic [3H] AMP. When p21 injection followed 90 min of insulin treatment, there was no increase in phosphodiesterase activity over that measured after hormone treatment or p21 injection alone, but additive effects of p21 and insulin on enzyme activity were observed during the first 90 min of insulin treatment. Even though normal Ha p21 and transforming [Val-12, Thr-59]Ha p21 stimulated oocyte phosphodiesterase to equal levels when coinjected with substrate at the initiation of the in vivo assay, the transforming protein elicited a more sustained stimulation of enzyme activity. These results suggest that stimulation of a cyclic AMP phosphodiesterase activity associated with insulin-induced maturation is involved in the growth-promoting actions of ras oncogene products in Xenopus oocytes.

Cellular mechanisms mediating the stimulation of ovine endometrial secretion of prostaglandin F2α in response to oxytocin: role of phospholipase C and diacylglycerol

1994 ◽  
Vol 141 (3) ◽  
pp. 481-490 ◽  
Author(s):  
W J Silvia ◽  
J-S Lee ◽  
D S Trammell ◽  
S H Hayes ◽  
L L Lowberger ◽  
...  
Keyword(s):  
Time Course ◽  
Prostaglandin F2α ◽  
Endometrial Tissue ◽  
Indole Derivatives ◽  
Cellular Mechanisms ◽  
Response Curves ◽  
The Relationship ◽  
Stimulation Of

Abstract The first objective was to describe and evaluate the relationship between the ability of oxytocin to stimulate the activity of phospholipase (PL) C and its ability to stimulate the release of prostaglandin (PG) F2α in ovine endometrial tissue. Caruncular endometrial tissue was collected from ovariectomized ewes after completion of an 11-day steroid replacement protocol. In experiment 1, explants were incubated either in the presence (10−6 m) or absence of oxytocin for 0, 1, 3, 10, 30 or 100 min to examine the time-course for activation of PLC and release of PGF2α in response to oxytocin. An increase in the activity of PLC was detected at 3 min while an increase in the release of PGF2α was not detected until 10 min (P<0·05). In experiment 2, explants were incubated in the presence of various oxytocin analogues (10−6 m) to compare their abilities to activate PLC and release PGF2α. Oxytocin and three receptor angonists stimulated the activity of PLC and the release of PGF2α (P<0·05) while two oxytocin receptor antagonists had no effect on either response. In experiment 3, explants were incubated in the presence of oxytocin or arginine vasopressin at 10−9 to 10−6 m to establish dose–response curves for the activation of PLC and release of PGF2α. For both hormones, significant increases (P<0·05) in the release of PGF2α were observed at 10−8 m while increases in PLC activity were not detected until 10−7 m was used. In experiment 4, explants were pretreated with either U-73122 (an inhibitor of PLC activity) or U-73343 (an inactive analogue of U-73122). Explants were then treated with control medium, oxytocin or AlF4−. Both oxytocin and AlF4− stimulated the activity of PLC and the release of PGF2α (P<0·05). U-73122 blocked the ability of oxytocin to stimulate the release of PGF2α (P<0·05) but had no effect on its ability to stimulate the activity of PLC (P>0·1). Based on the results from these experiments, the role of PLC in mediating the stimulatory effect of oxytocin on the release of PGF2α remains unclear. The second objective was to evaluate the role of diacylglycerol (DAG) in mediating the stimulatory effect of oxytocin on endometrial secretion of PGF2α. In experiment 5, explants were incubated in vitro with varying doses of two DAG analogues. Both analogues stimulated the release of PGF2α at 10−6 m (P<0·05), the highest dose tested. Corresponding inactive control compounds had no stimulatory effect. In experiment 6, explants were incubated with two synthetic DAGs and two indole-derived analogues of DAG. The indole derivatives stimulated the release of PGF2α. The synthetic DAGs were less effective in stimulating the release of PGF2α at the doses tested. In experiment 7, explants were preincubated with R59022 or LiCl. R59022 enhanced both the basal and oxytocin-stimulated released of PGF2α (P=0·07). LiCl promoted an increase in the accumulation of inositol trisphosphate (P<0·05) but had no effect on the release of PGF2α (P>0·5). These data indicate that DAG stimulates release of PGF2α from ovine endometrial tissue and may mediate the stimulatory effect of oxytocin on release of PGF2α. Journal of Endocrinology (1994) 141, 481–490

Sign in / Sign up

Export Citation Format

Share Document