Effects Of PGF2α Research Articles

Hormonal control of birth behavior in the Tasmanian devil Sarcophilus harrisii

In a number of marsupial species, females exhibit characteristic, stereotyped parturient behavior that facilitates the passage of the neonates to the pouch. In macropodids, this parturient behavior can be induced in non-pregnant females and males by treatment with either prostaglandin F2α (PGF2α) or oxytocin (OT). This study investigated the effects of PGF2α and OT on behavior of Tasmanian devils. Animals tended to sit or lie down quickly, with little vocalization, after treatment with PGF2α or OT, while after saline, the animals remained alert, seldom sat, and frequently vocalized. Hormone treatment caused increased respiration. Urogenital and pouch grooming, a characteristic element of parturient behavior in macropodids, was seen in only one devil after hormone treatment. However, no pouch or urogenital grooming was seen in videotape of a devil giving birth, so this may not be a feature of parturient behavior in this species. Overall behavior of males and females was very similar suggesting that the behavioral effects observed may be due to direct neural action of PGF2α or OT, rather than an indirect response to uterine or vaginal contractions caused by the hormones. This study is the first to demonstrate that OT results in PGF2α secretion as PGFM levels rose after OT injection.

An unexpected negative inotropic effect of prostaglandin F 2α in the rat heart

Prostaglandin F 2α (PGF 2α) is produced during myocardial inflammation and many of the insults that trigger contractile dysfunction also activate prostaglandin synthesis and production. However, although PGF 2α plays a significant role in the cardiac response to inflammation, the effect of this particular compound on the heart was largely studied at the cellular level and probably no due attention was paid to the effect of PGF 2α on the whole heart contractility. Therefore, in the present study we have investigated the effect of PGF 2α on isolated right ventricle of the rat heart. PGF 2α (1 nM–1 μM) induced concentration-dependent decrease of the amplitude of contractions of the ventricular muscle. Real time RT-PCR has revealed that prostaglandin FP receptors are expressed in the rat myocardium and the level of expression was similar to those of creatine kinase and adenylate kinase, which are proteins abundantly present in the heart. An antagonist of FP receptors, PGF 2α dimetilamide (10 nM), abolished negative inotropic effect induced by PGF 2α. To examine the possibility that PGF 2α could activate non-FP prostaglandin receptor, we have measured the level of expression of all known prostaglandin receptors in the rat heart. These experiments have shown that the order of expression of prostaglandin receptors in the rat heart is FP ≫ EP1 = TP > EP4 > EP3 > DP = IP. Based on the obtained results we conclude that PGF 2α induces negative inotropic effect on rat heart by activating FP prostaglandin receptors. This effect of PGF 2α could contribute to cardiac dysfunction in conditions of systemic and myocardial inflammation.

Does injection of prostaglandin F 2α (PGF 2α) cause ovulation in anestrous Western White Face ewes?

In a previous study in our laboratory, treatment of non-prolific Western White Face (WWF) ewes with PGF 2α and intravaginal sponges containing medroxyprogesterone acetate (MAP) on ∼Day 8 of a cycle (Day 0 = first ovulation of the interovulatory interval) resulted in ovulations during the subsequent 6 days when MAP sponges were in place. Two experiments were performed on WWF ewes during anestrus to allow us to independently examine if such ovulations were due to the direct effects of PGF 2α on the ovary or to the effects of a rapid decrease in serum concentrations of progesterone at PGF 2α-induced luteolysis. Experiment 1: ewes fitted with MAP sponges for 6 days ( n = 12) were injected with PGF 2α ( n = 6; 15 mg im), or saline ( n = 6) on the day of sponge insertion. Experiment 2: ewes received progesterone-releasing subcutaneous implants ( n = 6) or empty implants ( n = 5) for 5 days. Six hours prior to implant removal, all ewes received a MAP sponge, which remained in place for 6 days. Ewes from both experiments underwent ovarian ultrasonography and blood sampling once daily for 6 days before and twice daily for 6 days after sponge insertion. Additional blood samples were collected every 4 h during sponge treatment. Experiment 1: 4–6 (67%) PGF 2α-treated ewes ovulated ∼1.5 days after PGF 2α injection; these ovulations were not preceded by estrus or a preovulatory surge release of LH, and resulted in transient corpora hemorrhagica (CH). The growth phase was longer ( P < 0.05) and the growth rate slower ( P < 0.05) in ovulating versus non-ovulating follicles in PGF 2α-treated ewes. Experiment 2: in ewes given progesterone implants, serum progesterone concentrations reached a peak (1.72 ng/mL; P < 0.001) on the day of implant removal and decreased to basal concentrations (<0.17 ng/mL; P < 0.001) within 24 h of implant removal. No ovulations occurred in either the treated or the control ewes. We concluded that ovulations occurring after PGF 2α injection, in the presence of a MAP sponge, could be due to a direct effect of PGF 2α at the ovarian level, rather than a sudden decline in circulating progesterone concentrations.

Uteroglobin Inhibits Prostaglandin F2α Receptor-mediated Expression of Genes Critical for the Production of Pro-inflammatory Lipid Mediators

Prematurity is one of the leading causes of infant mortality. It may result from intrauterine infection, which mediates premature labor by stimulating the production of inflammatory lipid mediators such as prostaglandin F2alpha (PGF2alpha). The biological effects of PGF2alpha are mediated via the G protein-coupled receptor FP; however, the molecular mechanism(s) of FP signaling that mediates inflammatory lipid mediator production remains unclear. We reported previously that in the human uterus, a composite organ in which fibroblast, epithelial, and smooth muscle cells are the major constituents, an inverse relationship exists between the levels of PGF2alpha and a steroid-inducible anti-inflammatory protein, uteroglobin. Here we report that, in NIH 3T3 fibroblasts and human uterine smooth muscle cells, FP signaling is mediated via multi-kinase pathways in a cell type-specific manner to activate NF-kappaB, thus stimulating the expression of cyclooxygenase-2. Cyclooxygenase-2 is a critical enzyme for the production of prostaglandins from arachidonic acid, which is released from membrane phospholipids by phospholipase A2, the expression of which is also stimulated by PGF2alpha. Most importantly, uteroglobin inhibits FP-mediated NF-kappaB activation and cyclooxygenase-2 gene expression by binding and most likely by sequestering PGF2alpha into its central hydrophobic cavity, thereby preventing FP-PGF2alpha interaction and suppressing the production of inflammatory lipid mediators. We propose that uteroglobin plays important roles in maintaining homeostasis in organs that are vulnerable to inadvertent stimulation of FP-mediated inflammatory response.

Inhibitory effects of interferon-γ on myocardial hypertrophy

Prostaglandin F 2α (PGF 2α) plays an important role in pathologic cardiac growth. After testing several immune cytokines, we found that interferon-γ (IFN-γ) inhibited responsiveness of adult myocytes to PGF 2α. The present study was designed to test the hypothesis that IFN-γ inhibits cardiac hypertrophy induced by PGF 2α. Incubation of cultured adult rat cardiac myocytes with PGF 2α caused cell spreading, which was inhibited by IFN-γ. The inhibitory effect was not affected by nitric oxide (NO) synthase inhibitors. In addition, administration of fluprostenol, a more selective agonist at the PGF 2α receptor, induced cardiac hypertrophy in rats. Chronic treatment with IFN-γ inhibited this myocardial growth, and the inhibitory effect of IFN-γ was not accompanied by an increase in myocardial NO synthase gene expression. Further, abdominal aortic constriction resulted in a substantial increase in heart, ventricular and left ventricular weights to BW ratio that was significantly attenuated by treatment with IFN-γ. The results demonstrate that IFN-γ inhibits the in vitro and in vivo effects of PGF 2α on cardiac hypertrophy, and that the mechanism of action is likely independent of NO production. IFN-γ also attenuated cardiac hypertrophy induced by pressure overload, suggesting that PGF 2α plays a role in the pathogeneses of this severe type of cardiac hypertrophy.

A Positive Feedback Loop that Regulates Cyclooxygenase-2 Expression and Prostaglandin F2α Synthesis via the F-Series-Prostanoid Receptor and Extracellular Signal-Regulated Kinase 1/2 Signaling Pathway

Cyclooxygenase (COX) enzymes catalyze the biosynthesis of eicosanoids, including prostaglandin (PG) F2alpha. PGF2alpha exerts its autocrine/paracrine function by coupling to its G protein-coupled receptor [F-series-prostanoid (FP) receptor] to initiate cell signaling and target gene transcription. In the present study, we found elevated expression of COX-2 and FP receptor colocalized together within the neoplastic epithelial cells of endometrial adenocarcinomas. We investigated a role for PGF2alpha-FP receptor interaction in modulating COX-2 expression and PGF2alpha biosynthesis using an endometrial adenocarcinoma cell line stably transfected with the FP receptor cDNA (FPS cells). PGF2alpha-FP receptor activation rapidly induced COX-2 promoter, mRNA, and protein expression in FPS cells. These effects of PGF2alpha on the expression of COX-2 could be abolished by treatment of FPS cells with an FP receptor antagonist (AL8810) and chemical inhibitor of ERK1/2 kinase (PD98059), or by inactivation of ERK1/2 signaling with dominant-negative mutant isoforms of Ras or ERK1/2 kinase. We further confirmed that elevated COX-2 protein in FPS cells could biosynthesize PGF2alpha de novo to promote a positive feedback loop to facilitate endometrial tumorigenesis. Finally, we have shown that PGF2alpha could potentiate tumorigenesis in endometrial adenocarcinoma explants by inducing the expression of COX-2 mRNA.

Blood flow: A key regulatory component of corpus luteum function in the cow

Prostaglandin F2α (PGF 2α) is the primary luteolysin in the cow. During the early luteal phase, the corpus luteum (CL) is resistant to the luteolytic effect of PGF 2α. Once mature, the CL becomes responsive to PGF 2α and undergoes luteal regression. These actions of PGF 2α coincide with changes in luteal blood flow (BF): PGF 2α has no effect on BF in the early CL, but acutely increases BF in the peripheral vasculature of the mature CL within 30 min of PGF 2α injection. During spontaneous luteolysis, luteal BF increases on Days 17–18 of the estrous cycle, prior to any decrease in plasma progesterone (P). The increase in luteal BF is synchronous with an increase in plasma PGFM levels, suggesting that pulsatile release of PGF 2α from uterus stimulates the increase in luteal BF. Serial biopsies of these CL showed that mRNA expression for endothelial nitric oxide synthase (eNOS) together with endothelin-1 (ET-1) and angiotensin converting enzyme (ACE) increases on Days 17–18 when the luteal BF is elevated. On Day 19 when plasma P level firstly decreases, eNOS mRNA returns to the basal level whereas ET-1 and ACE mRNA remains elevated. Cyclooxygenase-2 (COX-2) mRNA expression increases on Day 19. In support of these data, an in vivo microdialysis study revealed that luteal ET-1 and angiotensin II (Ang II) secretion increases and precedes PGF 2α secretion during spontaneous luteolysis. In conclusion, we show for the first time that an acute increase of BF occurs in the peripheral vasculature of the mature CL together with increases in eNOS expression and ET-1 and Ang II secretion in the CL during the early stages of luteolysis in the cow. We propose that the increase in luteal BF may be induced by NO from large arterioles surrounding the CL, and simultaneously uterine or exogenous PGF 2α directly increases ET-1 and Ang II secretion from endothelial cells of microcapillary vessels within the CL, thereby suppressing P secretion by luteal cells. Taken together, our results indicate that an acute increase in luteal BF occurs as a first step of luteolysis in response to PGF 2α. Therefore, local BF plays a key role to initiate luteal regression in the cow.

Effects of PGF 2α on human melanocytes and regulation of the FP receptor by ultraviolet radiation

Prostaglandins are potent lipid hormones that activate multiple signaling pathways resulting in regulation of cellular growth, differentiation, and apoptosis. In the skin, prostaglandins are rapidly released by keratinocytes following ultraviolet radiation and are chronically present in inflammatory skin lesions. We have shown previously that melanocytes, which provide photoprotection to keratinocytes through the production of melanin, express several receptors for prostaglandins, including the PGE 2 receptors EP 1 and EP 3 and the PGF 2α receptor FP, and that PGF 2α stimulates melanocyte dendricity. We now show that PGF 2α stimulates the activity and expression of tyrosinase, the rate-limiting enzyme in melanin synthesis. Analysis of FP receptor regulation showed that the FP receptor is regulated by ultraviolet radiation in melanocytes in vitro and in human skin in vivo. We also show that ultraviolet irradiation stimulates production of PGF 2α by melanocytes. These results show that PGF 2α binding to the FP receptor activates signals that stimulate a differentiated phenotype (dendricity and pigmentation) in melanocytes. The regulation of the FP receptor and the stimulation of production of PGF 2α in melanocytes in response to ultraviolet radiation suggest that PGF 2α could act as an autocrine factor for melanocyte differentiation.

Prostaglandin F2$alpha; (PGF2$alpha;) independent and dependent regulation of the bovine luteal endothelin system

We have examined the genes of the endothelin system that are targets for regulation by prostaglandin F2α (PGF2α). The effects of a luteolytic dose of PGF2α on the mRNA encoding endothelin converting enzyme-1 (ECE-1), pre-pro endothelin-1 (pp ET-1) and the ET receptors ETA, ETB, in bovine corpus luteum (CL) during the early (days 1 and 4), mid (day 10) or late (day 17) luteal phases were examined. The effect of the PGF2α treatment on ECE-1 protein, Big ET-1 and the biologically active mature ET-1 peptide were also examined. Most importantly, the direct ECE-1 activity was determined. Before day 10 of the cycle, in a PGF2α-independent manner, the amounts of mRNA encoding ET-1, ECE-1, ETA, and ETB were increased steadily from day 1. After day 10 of the cycle, expression of mRNA encoding pp ET-1 and ETA acquired responsiveness to exogenous PGF2α and both genes were up-regulated by the PGF2α treatment. This effect of PGF2α was also detected for the proteins corresponding to the mature ET-1. The enzymatic activity of ECE-1 remained unchanged throughout the lifespan of the CL in spite of the detected changes in mRNA and protein. The results suggest that the luteal endothelin system is regulated in a PGF2α-independent and -dependent manner. Importantly, an alteration in luteal ET-1 availability is most likely achieved by modulating the expression of mRNA encoding pp ET-1 and not by the amount or activity of ECE-1. This interpretation is supported by the observation that the activity of ECE-1 remained unchanged throughout the ovarian cycle. The combined effects of greater ET-1 availability and gene expression encoding the ETA receptor in the late luteal phase could render the CL, at this developmental stage, more sensitive or responsive to ET-1. If the luteal tissue is responsive to the available ET-1 during the early phase of the ovarian cycle, an additional role for ET-1 should be considered beyond mediating the luteolytic actions of PGF2α. Agents blocking the actions of ET-1 might be the best approach to interfere with the luteal ET system and test its physiological role(s) in vivo.

A sheer pharmacologic approach to compare the contractile effects of PGF 2α, dl-cloprostenol and d-cloprostenol on isolated uterine, tracheal, ileal and arterial smooth muscle preparations

The contractile effects of PGF 2α and its cloprostenol analogs ( d-enantiomer and racemate) were examined on isolated smooth muscle preparations (uterine, tracheal, ileal and arterial) from rat, guinea-pig and horse. dl- and d-cloprostenol were potent contractors of myometrium, but had negligible secondary effects on other types of smooth muscle, except artery whose response to the d-enantiomer may give rise to some concern.

Prostaglandin F2α (PGF 2α) independent and dependent regulation of the bovine luteal endothelin system

We have examined the genes of the endothelin system that are targets for regulation by prostaglandin F 2α (PGF 2α). The effects of a luteolytic dose of PGF 2α on the mRNA encoding endothelin converting enzyme-1 (ECE-1), pre-pro endothelin-1 (pp ET-1) and the ET receptors ET A, ET B, in bovine corpus luteum (CL) during the early (days 1 and 4), mid (day 10) or late (day 17) luteal phases were examined. The effect of the PGF 2α treatment on ECE-1 protein, Big ET-1 and the biologically active mature ET-1 peptide were also examined. Most importantly, the direct ECE-1 activity was determined. Before day 10 of the cycle, in a PGF 2α-independent manner, the amounts of mRNA encoding ET-1, ECE-1, ET A, and ET B were increased steadily from day 1. After day 10 of the cycle, expression of mRNA encoding pp ET-1 and ET A acquired responsiveness to exogenous PGF 2α and both genes were up-regulated by the PGF 2α treatment. This effect of PGF 2α was also detected for the proteins corresponding to the mature ET-1. The enzymatic activity of ECE-1 remained unchanged throughout the lifespan of the CL in spite of the detected changes in mRNA and protein. The results suggest that the luteal endothelin system is regulated in a PGF 2α-independent and -dependent manner. Importantly, an alteration in luteal ET-1 availability is most likely achieved by modulating the expression of mRNA encoding pp ET-1 and not by the amount or activity of ECE-1. This interpretation is supported by the observation that the activity of ECE-1 remained unchanged throughout the ovarian cycle. The combined effects of greater ET-1 availability and gene expression encoding the ET A receptor in the late luteal phase could render the CL, at this developmental stage, more sensitive or responsive to ET-1. If the luteal tissue is responsive to the available ET-1 during the early phase of the ovarian cycle, an additional role for ET-1 should be considered beyond mediating the luteolytic actions of PGF 2α. Agents blocking the actions of ET-1 might be the best approach to interfere with the luteal ET system and test its physiological role(s) in vivo.

Prostaglandin F 2α increases glucose transport in 3T3-L1 adipocytes through enhanced GLUT1 expression by a protein kinase C-dependent pathway

The effect of prostaglandin F 2α (PGF 2α) on glucose transport in differentiated 3T3-L1 adipocytes was examined. Whereas PGF 2α had little influence on insulin-stimulated 2-deoxyglucose uptake, it increased basal glucose uptake in a time- and dose-dependent manner, reaching maximum at approximately 8 h. The long-term effect of PGF 2α on glucose transport was inhibited by both cycloheximide and actinomycin D. In concord, while the content of GLUT4 protein was not altered, immunoblot and Northern blot analyses revealed that both GLUT1 protein and mRNA levels were increased by exposure of cells to PGF 2α. The effect of PGF 2α on glucose uptake was inhibited by GF109203X, a selective protein kinase C (PKC) inhibitor. In addition, in cells depleted of diacylglycerol-sensitive PKC by prolonged treatment with 4β-phorbol 12β-myristate 13α-acetate (PMA), the stimulatory effects of PGF 2α on glucose transport and GLUT1 mRNA accumulation were both inhibited. In accord, PMA was shown to stimulate GLUT1 mRNA accumulation. To further investigate if PKC may be activated by PGF 2α, we tested several diacylglycerol-sensitive PKC isozymes and found that PGF 2α was able to activate PKCε. Taken together, these results indicate that PGF 2α may enhance glucose transport in 3T3-L1 adipocytes by stimulating GLUT1 expression via a PKC-dependent mechanism.

Stimulatory effect of prostaglandin F 2α on Na-dependent phosphate transport in osteoblast-like cells

Prostaglandin F 2α (PGF 2α) has been reported to activate protein kinase C (PKC) through both phospholipase (PL) C and D, resulting in the proliferation of osteoblast-like cells. In addition, it has also been reported that Erk mitogen-activated protein kinase is also involved in the mechanism of PGF 2α-induced proliferation of these cells. Recently, we have reported that several growth factors stimulate Na-dependent phosphate transport (Pi transport) activity of osteoblast-like cells, which has been recognized to play an important role in their mineralization. In the present study, we investigated the effect of PGF 2α on Pi transport in MC3T3-E1 osteoblast-like cells. PGF 2α stimulated Na-dependent Pi transport dose dependently in the range between 1 nM and 10 μM in MC3T3-E1 cells. The effect was time dependent up to 24 h. Kinetic analysis revealed that PGF 2α induces newly synthesized Pi transporter. Pretreatment with actinomycin D and cycloheximide suppressed PGF 2α-induced enhancement of Pi transport. Combined effect of PMA and PGF 2α was not additive in Pi transport. Calphostin C, a PKC inhibitor, dose-dependently suppressed Pi transport induced by PGF 2α. On the contrary, U0126, which inhibits an upstream kinase of Erk (MEK), did not affect PGF 2α-induced enhancement of Pi transport. In conclusion, PGF 2α stimulates Pi transport through activation of PKC in osteoblast-like cells.

Prostaglandin F 2α stimulates tyrosine phosphorylation of phospholipase C-γ1

In this study, we investigated the ability of prostaglandin F 2α (PGF 2α) to induce tyrosine phosphorylation of phospholipase C-γ1 (PLC-γ1) in cat iris sphincter smooth muscle (CISM) cells. PGF 2 α (1 μM) stimulated PLC-γ1 tyrosine phosphorylation in a time- and dose-dependent manner with a maximum increase of 3-fold at 0.5 min. The protein tyrosine kinase inhibitors, genistein, and tyrphostin A-25, blocked the stimulatory effects of PGF 2α, suggesting involvement of protein tyrosine kinase activity in the physiological actions of the PGF 2α. Furthermore, PGF 2α-induced p42/p44 MAP kinase activation was also completely blocked by protein tyrosine kinase inhibitors. In summary, these findings show that PGF 2α stimulates tyrosine phosphorylation of PLC-γ1 in CISM cells and indicate that PGF 2α-stimulated tyrosine phosphorylation is responsible for an early signal transduction event.

Postovulatory effect of repeated administration of prostaglandin F 2α on the endocrine status, ova transport, binding of accessory spermatozoa to the zona pellucida and embryo development of recently ovulated sows

We investigated the postovulatory effect of repeated administration of prostaglandin F 2α (PGF 2α) on the endocrine status, ova transport, binding of accessory spermatozoa to the zona pellucida (ZP) and embryo development of recently ovulated sows. We used altogether 10 Swedish crossbred (Landrace×Yorkshire) multiparous sows. The treatment group (P-group) was administered 1 mg of PGF 2α intravenously every 6 h via an indwelling jugular cannula, commencing 4–8 h after ovulation was detected in the second estrus after weaning. All sows were inseminated once and blood was sampled until the end of the experimental period. After slaughter, we immediately recovered the reproductive tracts and divided them into three equal isthmic segments (IST1, IST2 and IST3) and a third of the uterine horn from the utero-tubal-junction (UTJ), and we flushed each one with PBS for ova recovery. We immediately stained the ova and examined them under epi-fluorescence illumination. We found the highest proportion of ova in the P-group in IST1 (41.5%), while we found the highest proportion in the C-group in the uterus (40.7%). A total of 68.7% of ova in the P-group had more than 50 accessory spermatozoa attached to the ZP, compared with 36.7% in the C-group sows. A total of 77% of ova had more than three blastomeres in the P-group, compared with 73% in the C-group. PGF 2α metabolite and cortisol levels were elevated ( P<0.05) following every PGF 2α administration. Despite peaks, we saw no changes ( P>0.05) in progesterone levels between the P-group and the C-group. We saw no differences ( P>0.05) in estradiol-17β levels between the P-group and the C-group. We concluded that PGF 2α stimulates the hypothalamus–pituitary–adrenal axis, as evidenced by the elevation of cortisol and progesterone but not estradiol-17β. Furthermore, repeated PGF 2α administration might be associated with a delayed ova transport and an increased number of accessory spermatozoa bound to the ZP. However, the effect of PGF 2α on embryo development is unclear.

PGF 2α-induced nest building and choice behaviour in female domestic pigs

The domestic pig, Sus scrofa, builds a maternal nest in the day before parturition. A model for porcine nest building has been established, in which exogenously administered prostaglandin (PG)F 2α is used to induce nesting behaviour in cyclic, pseudopregnant and pregnant pigs. This experiment was designed to examine the effect of PGF 2α on the preferences of non-pregnant gilts for pens bedded with straw compared with bare pens. Ten 6-month-old nulliparous female pigs (gilts) were tested in an arena, which consisted of four pens ( 1.8 m×1.7 m), a neutral area ( 1.5 m×3.4 m) and a start area ( 1.5 m×3.4 m). Two of the pens contained 2 kg of fresh straw and the remainder of the testing arena was devoid of straw. On the first day of testing half of the pigs were given a control intramuscular injection of 3 ml 0.9% saline and the remainder were given an intramuscular injection of 15 mg PGF 2α and their behaviour scored for 1 h after treatment. On the following day the treatments were reversed, such that each pig was given both treatments (saline or PGF 2α). There was no significant effect of the order of treatment on behaviour. After saline-treatment the pigs spent most of their time in the pens containing straw (59%) and the least amount of time in bare pens (5%). In the straw pens, saline-treatment induced bouts of oronasal contact with straw of a relatively long duration (11–100 s), which we interpret as foraging. In the hour after PGF 2α-treatment the pigs also spent most of their time in the pens containing straw (44%) and the least amount of time in bare pens (10%), but they interacted with the straw in a markedly different way. PGF 2α-treated pigs displayed bouts of oronasal contact with straw of a relatively short duration (2–10 s) which, together with high frequencies of pawing at straw, lifting and carrying straw in the mouth, we interpret as nest building behaviour. Superimposed on this is the finding that gilts spend more time in the neutral areas after PGF 2α-treatment than they did after saline-treatment. PGF 2α-treated pigs spent most of their time engaged in nesting behaviour within the straw pens but they also gathered and deposited straw in different areas of the test arena (neutral and start areas); behaviours not seen after saline-treatment. We conclude that pigs generally prefer a pen containing straw bedding to a bare pen but that PGF 2α alters the way they interact with straw, inducing behaviour similar to prepartum nest building.

PGF 2α facilitates the training of sexuality active boars for semen collection

The objective was to determine the effects of PGF 2α on the training of sexually active boars (i.e., boars experienced with natural mating) to mount an artificial sow for semen collection. Boars were moved to a semen collection pen twice weekly for 4 wk. After entering the pen, boars received im treatment with 10 mg PGF 2α (n = 7) or 2 mL deionized water (n = 7). Boars were classified as trained when after a successful collection, the animals mounted the artificial sow and allowed semen collection on the next scheduled day without first receiving an injection of PGF 2α or deionized water. The semen from 6 of 7 PGF 2α-treated boars and 2 of 7 control boars was collected during the first exposure to the artificial sow (P < .03). After 4 training sessions, 7 of 7 PGF 2α-treated boars and 4 of 7 controls were successfully trained (P < .05). The number of false mounts (mounting artificial sow but not allowing semen collection) per session was lower (P < .07) for PGF 2α-treated boars (.6 ± 1.0), compared to boars receiving deionized water (3.9 ± 1.0) or trained boars receiving no treatment (3.4 ± .7). Reaction time (elapsed time after entering collection pen until the start of ejaculation) was lower (P < .04)_ for PGF 2α-treated boars (267.4 ± 63.4 sec), compared to boars treated with deionized water (628.4 ± 98.3 sec) or boars receiving no treatment (440.4 ± 46.4 sec). In summary, use of PGF 2α facilitated the training of sexually active boars to mount an artificial sow for semen collection.

Effects of PGF2α and GnRH during Different Ovarian Status at Onset of Puberty in Murrah Buffalo Heifers (Bubalus bubalis)

Effects of PGF2α and GnRH during Different Ovarian Status at Onset of Puberty in Murrah Buffalo Heifers (Bubalus bubalis)

Effect of PGF 2α, indomethacin, tamoxifen, or estradiol-17β on incidence of abortion, progesterone, and pregnancy-specific protein B (PSPB) secretion in 88- to 90-day pregnant sheep☆

One objective of this experiment was to evaluate our hypotheses that estradiol-17β regulates secretion of pregnancy specific protein B (PSPB) and that secretion of progesterone during pregnancy is regulated by a prostanoid by examining the effects of prostaglandin F 2α (PGF 2α), a luteolyic agent; indomethacin, a prostanoid synthesis inhibitor; tamoxifen, an estrogen receptor antagonist; estradiol 17-β; and interaction of these factors on the incidence of abortion and progesterone and PSPB secretion. Another objective was to determine if there is a luteal source of PSPB. Weights of corpora lutea were decreased ( P ≤ 0.05) by PGF 2α, indomethacin, PGF 2α + tamoxifen, PGF 2α + indomethacin, and PGF 2α + estradiol-17β but not ( P ≥ 0.05) by tamoxifen or estradiol-17β alone. No ewe treated with PGF 2α alone aborted ( P ≥ 0.05). Forty percent of ewes treated with PGF 2α + estradiol-17β aborted ( P ≤ 0.05), but ewes were not aborted by any other treatment within the 72-h sampling period. Profiles of progesterone in jugular venous blood differed ( P ≤ 0.05) among control, indomethacin-, tamoxifen-, and PGF 2α + indomethacin-treated ewes. Progesterone in jugular venous blood of control ewes decreased ( P ≤ 0.05) by 24 h, followed by a quadratic increase ( P ≤ 0.05) from 24 to 62 h. Progesterone in jugular venous blood of indomethacin-, PGF 2α-, PGF 2α + tamoxifen-, PGF 2α + indomethacin-, PGF 2α + estradiol-17β-, and tamoxifen-treated ewes was reduced ( P ≤ 0.05) by 18 h and did not vary ( P ≥ 0.05) for the remainder of the 72-h sampling period. Progesterone in vena cava and in uterine venous blood was reduced ( P ≤ 0.05) at 72 h in PGF 2α-, indomethacin-, tamoxifen-, PGF 2α + indomethacin-, PGF 2α + tamoxifen-, and PGF 2α + estradiol-17β-treated ewes. Weights of placentomes did not differ among treatment groups ( P ≥ 0.05). Profiles of PSPB in inferior vena cava blood differed ( P ≤ 0.05) among control, estradiol-17β-, indomethacin-, tamoxifen-, PGF 2α + indomethacin-, and PGF 2α + tamoxifen-treated 88- to 90-day pregnant ewes. Concentrations of PSPB in inferior vena cava blood were increased ( P ≤ 0.05) in indomethacin-, estradiol-17β-, tamoxifen-, PGF 2α + tamoxifen-, and PGF 2α + indomethacin-treated 88- to 90-day pregnant ewes within 6 h and did not vary ( P ≥ 0.05) for the remainder of the 72-h sampling period. Concentrations of PSPB in uterine venous blood of indomethacin-, tamoxifen-, PGF 2α + tamoxifen-, and PGF 2α + indomethacin-treated ewes were greater ( P ≤ 0.05) at 72 h than at 0 h. PSPB in ovarian venous blood did not differ ( P ≥ 0.05) adjacent or opposite to the ovary with the corpus luteum. It is concluded from these data that estrogen regulates placental secretion of PSPB and that a prostanoid, presumably prostaglandin E, regulates placental secretion of progesterone during 88–90 days of gestation in sheep and that there is no luteal source of PSPB.

Progesterone receptor is not required for progesterone action in the rat corpus luteum of pregnancy ☆

In this study, we investigated whether progesterone exerts a local action regulating the function of the corpus luteum of pregnancy in rats. The luteal activities of the enzymes 3β-hydroxysteroid dehydrogenase (3β-HSD), involved in progesterone biosynthesis, and 20α-hydroxysteroid dehydrogenase (20α-HSD), that catabolizes progesterone and reduces progesterone secretion by the corpus luteum, were evaluated after intrabursal ovarian administration of progesterone in pregnant rats that had received a luteolytic dose of prostaglandin F 2α (PGF 2α). Luteal 3β-HSD activity decreased and 20α-HSD activity increased after PGF 2α treatment (100 μg × 2 intraperitoneally on Day 19 of pregnancy at 12:00 p.m. and 4:00 p.m.) when compared with controls sacrificed at 8:00 p.m. on Day 20 of pregnancy. This effect of PGF 2α on the luteal 3β-HSD and 20α-HSD activities was abolished in animals that also received an intraovarian dose of progesterone (3 μg/ovary on Day 19 of pregnancy at 8:00–9:00 a.m.). In a second functional study, luteal cells obtained from 19-day pregnant rats responded to the synthetic progestin promegestone (R5020) in a dose-dependent manner, with an increase in the progesterone output. In addition, the glucocorticoid agent hydrocortisone did not affect progesterone accumulation in the same luteal cell culture. We also examined by immunocytochemistry the expression of progesterone receptors (PR) in the corpora lutea during pregnancy and demonstrated the absence of PR in this endocrine gland in all the days of pregnancy studied. In the same pregnant rats, positive staining for PR was observed in cells within the uteroplacental unit, such as cells of the decidua basalis and trophoblast giant cells of the junctional zone. In addition, positive PR staining was observed in the ovarian granulosa and theca cells of growing follicles, but not in corpora lutea of ovaries obtained from cycling rats at proestrus. In summary, this report provides further evidence of a local action of progesterone regulating luteal function in the rat despite the absence of a classic PR.