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PubMed2004

Increasing feed intake in late gestation does not affect plasma progesterone concentration in the sow.

Rate of decline in plasma progesterone concentration may influence the success of lactogenesis in the sow. The aim of this experiment was to investigate whether progesterone concentration and rate of decline of progesterone in the periparturient sow could be manipulated by changing her feeding level. Forty-two sows received either 1.15 or 2 times maintenance energy daily from day 100 of gestation up until and including the day of farrowing. Blood samples were taken on days 98 (pre-treatment baseline) and 109 of gestation, during farrowing, 6h after farrowing and at 09:00 h for the 3 days following farrowing. Plasma progesterone concentration was determined and progesterone half-life was calculated for each sow. High intake feeding had no effect on plasma progesterone concentration at any time of sampling. Progesterone half-life averaged 41.2 +/- 3.81 h and did not differ between treatments. There was no relationship between progesterone concentration, or half-life, and litter weight gain, although there was a weak correlation between decline in progesterone in the first 6h after birth and piglet growth rate from birth to 6 days of age (R(2) = 0.109, P < 0.05). It was concluded that increasing feed intake in late gestation cannot be used to increase progesterone clearance rate and hasten the onset of lactogenesis in sows.

Animals↗
PubMed2005

Post-insemination milk progesterone concentration and embryo survival in dairy cows.

Logistic regression analysis was used to evaluate the relationship between post-insemination milk progesterone concentration and embryo survival, and between milk yield and milk progesterone concentration. Milk samples were collected on Days 1, 4, 5, 6, and 7 (insemination=Day 0) following 871 inseminations in spring-calving dairy cows. Milk progesterone concentrations were measured by enzyme-immunoassay and pregnancy diagnosis was conducted with transrectal ultrasonography at approximately Day 30. There was a negative linear relationship (P<0.01) between milk progesterone concentration on Day 4 and embryo survival while, in contrast, there was a positive linear and quadratic relationship between milk progesterone concentration on Days 5, 6 and 7 (P<0.05) and also between the rate of change in progesterone concentrations between Days 4 and 7 inclusive and embryo survival (P<0.05). There was a weak negative linear relationship between average daily milk yield at the time of insemination and milk progesterone concentrations (P<0.001). There was no association between many production parameters, including liveweight and body condition score measured at various stages between calving and insemination, and milk progesterone concentration between Days 4 and 7 inclusive (P>0.05). In conclusion, low progesterone during Days 5-7 (after insemination) was associated with low fertility in dairy cows and there were indications of a range of progesterone concentrations within which embryo survival was maximal.

Animals↗
PubMed1998

Expression of gelatinase B by trophoblast cells: down-regulation by progesterone.

OBJECTIVE: It is now accepted that gelatinase B (92 kd type IV collagenase) is involved in blastocyst implantation and trophoblast invasion. However, little is known about the regulation of this enzyme at the fetomaternal interface. Progesterone has been demonstrated to inhibit gelatinase B secretion from endometrial cells, myometrium, and cervical fibroblasts. Interestingly, the promotor of gelatinase B contains a progesterone-responsive element that may explain transcriptional activation of this metalloproteinase by progesterone. It may be hypothesized that progesterone secreted from trophoblast cells, representing the fetal part of the fetomaternal interface, may have a role in the regulation of gelatinase secretion and blastocyst implantation. STUDY DESIGN: To this end, use was made of first-trimester trophoblast cells obtained from first-trimester pregnancy terminations. The trophoblast cells were separated by trypsin degradation and fractionation on Percoll gradients. Metalloproteinase activity was measured by zymography, and the expression of the gelatinase B messenger ribonucleic acid was determined by the solution hybridization/ribonuclease protection assay. RESULTS: Primary cell cultures of trophoblasts from first trimesters of pregnancy constitutively elaborated two species of type IV collagenases (gelatinase A and B) as assessed on a gelatin matrix. Treatment with progesterone decreased the accumulation of a gelatinase B species in a dose-dependent fashion. Administration of a progesterone receptor antagonist onapristone (ZK-98.299) neutralized the progesterone inhibitory effect on the gelatinase B in a dose-dependent fashion, thus supporting the presumption that the progesterone effect is receptor mediated. Progesterone significantly attenuated the expression of gelatinase B by trophoblast cells, an effect that was neutralized by ZK-98.299. CONCLUSION: These observations provide strong indirect support for the participation of progesterone in the regulation of gelatinase B in trophoblast cells. It may be an important regulator of gelatinase production at the fetomaternal interface.

Cells, Cultured↗
PubMed2003

Progesterone attenuates the effect of the 5-HT1A receptor agonist, 8-OH-DPAT, and of mild restraint on lordosis behavior.

Ovariectomized, hormone-primed rats were used to test the hypothesis that progesterone treatment attenuated the effects of the 5-HT(1A) receptor agonist, (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on female rat lordosis behavior. Based upon prior evidence that prepriming with estradiol benzoate (EB) reduced the ability of 8-OH-DPAT to inhibit lordosis behavior, rats were preprimed with 10 microg EB 7 days before a second priming with 10 microg EB followed 48 h later with 500 microg progesterone or vehicle. Independent of the presence of progesterone, prepriming with EB attenuated the lordosis-inhibiting effects of systemic treatment with 8-OH-DPAT. However, progesterone also reduced the effects of 8-OH-DPAT and this effect was also seen in females primed only once with EB. In contrast, progesterone was relatively ineffective in attenuating the effects of bilateral infusion with 8-OH-DPAT into the ventromedial nucleus of the hypothalamus (VMN). The failure of progesterone to substantially reduce the effects of VMN infusion with 8-OH-DPAT contrasts with prior studies in which estrogen's protective action against the drug did include the VMN. Thus, while both estrogen and progesterone reduce the lordosis-inhibiting effect of 8-OH-DPAT, the mechanisms responsible for the effects of the two gonadal hormones may be different. Priming with progesterone also prevented the effects of 5 min of restraint. When rats were hormonally primed with EB and oil, rats showed a transient, but significant, decline in lordosis behavior 5 and 10 min after restraint. Rats primed with EB and progesterone were unaffected by the restraint. These results are discussed in terms of their implications for the role of progesterone in altering the 5-HT(1A) receptor modulation of lordosis behavior.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Regulation of cyclic AMP level by progesterone in ovariectomized rat neocortex.

Exposure of neocortical slices to progesterone, without prior treatment with estrogen, augmented forskolin-induced cyclic AMP within 15 min. 30 nM progesterone produced approximately 1/2 the maximal effect but as little as 10 nM progesterone produced a detectable increase in cyclic AMP. When forskolin was replaced by dideoxyforskolin, an analog that does not directly stimulate adenylyl cyclase but shares many of its other actions, progesterone did not augment cyclic AMP. Progesterone also failed to affect increased cyclic AMP that followed exposure to norepinephrine or isoproterenol. The effect of progesterone upon cyclic AMP was also evident when tetrodotoxin was added to block voltage-dependent sodium channels, suggesting that intercellular communication that is dependent upon action potentials was not necessary. The effect of progesterone was at least partially blocked by antagonists of GABAA receptor action, suggesting the involvement of GABAA or GABAA-like receptors. The effect of progesterone was also not homogeneous over the neo cortex. While forskolin-stimulated cyclic AMP was augmented by progesterone in the parietal and occipital regions, it was suppressed in the frontal region. These results are envisioned as a progesterone action upon a small and perhaps compartmentalized component of the cellular cyclic AMP system, an effect that is made detectable in our whole-tissue assay by the well known ability of forskolin to potentiate many hormonal effects upon cyclic AMP.

Animals↗
PubMed1999

Use of Crinone vaginal progesterone gel for luteal support in in vitro fertilization cycles.

OBJECTIVE: To investigate the efficacy and safety of intravaginal Crinone 8% (Columbia Research Laboratories, Miami. FL) versus IM progesterone for luteal phase support after IVF-ET. DESIGN: Prospective open trial with comparison to historical controls. SETTING: University hospital. PATIENT(S): Two hundred six women undergoing IVF-ET. INTERVENTION(S): One hundred patients received Crinone vaginal progesterone gel (90 mg once daily) and 106 patients received IM progesterone (50 mg once daily) beginning on the evening of oocyte retrieval. MAIN OUTCOME MEASURE(S): Pregnancy and miscarriage rates, and midluteal serum progesterone levels. RESULT(S): Positive beta-hCG pregnancy rates, clinical pregnancy rates per transfer, and ongoing pregnancy rates were similar for the Crinone and IM progesterone groups. Women who received Crinone had higher rates of biochemical pregnancy loss but lower rates of clinical pregnancy loss (i.e., spontaneous abortion) than women who received IM progesterone. Midluteal serum progesterone concentrations were significantly higher in the IM progesterone group (94.3+/-8.8 ng/mL versus 57.7+/-7.4 ng/mL). Several women who received Crinone had vaginal bleeding 11-13 days after oocyte retrieval. CONCLUSION(S): For all age categories, positive beta-hCG and ongoing pregnancy rates were similar when Crinone or IM progesterone was given for luteal phase support in IVF-ET cycles, despite lower serum progesterone concentrations and higher rates of biochemical pregnancy loss with Crinone. Although the results of this study support the use of Crinone as an acceptable alternative for luteal support after IVF-ET, differences in bleeding patterns and rates of biochemical pregnancy loss demonstrate the need for a prospective randomized study.

Administration, Intravaginal↗
PubMed1999

Crinone 8% vaginal progesterone gel results in lower embryonic implantation efficiency after in vitro fertilization-embryo transfer.

OBJECTIVE: To evaluate the outcome of IVF-ET after the use of Crinone 8% (Wyeth-Ayerst Laboratories, Inc., Philadelphia, PA) vaginal progesterone gel and to compare these results with those seen in our program with the use of IM progesterone-in-oil. DESIGN: Retrospective cohort study. SETTING: A tertiary referral reproductive medicine unit. PATIENT(S): Patients <40 years of age undergoing IVF-ET cycles. INTERVENTION(S): Patients were treated with either Crinone 8% vaginal progesterone gel (90 mg) administered daily or IM progesterone-in-oil (50 mg) administered daily. MAIN OUTCOME MEASURE(S): Biochemical pregnancy rate, implantation rate, and clinical and ongoing pregnancy rates. RESULT(S): The use of Crinone 8% vaginal progesterone gel was associated with a lower implantation rate (16.6% versus 26.2%; odds ratio [OR] = 0.56; 95% confidence interval [CI], 0.35-0.89) compared with the use of IM progesterone-in-oil. Biochemical pregnancies were more common after the use of Crinone 8% vaginal progesterone gel as defined by either biochemical pregnancies per transfer (15.9% versus 5.7%; OR = 3.11; 95% CI, 1.17-8.32) or biochemical pregnancies as a proportion of positive serum hCG titers (29.2% versus 9.8%; OR = 3.80; 95% CI, 1.33-10.86). Clinical pregnancy rates also were lower with the use of Crinone 8% vaginal progesterone gel (36.4% versus 52.9%; OR = 0.51; 95% CI, 0.26-0.99). CONCLUSION(S): Implantation efficiency is reduced, as demonstrated by lower embryonic implantation rates and higher biochemical pregnancy rates, when Crinone 8% vaginal progesterone gel rather than IM progesterone-in-oil is used for luteal phase support after IVF-ET.

Administration, Intravaginal↗
PubMed1998

Regulation of uterine immune function by progesterone--lessons from the sheep.

Survival of the fetal allograft results from orchestrated adjustments in activity of maternal lymphoid cells as well as in trophoblast gene expression. One molecule that regulates uterine immune responsiveness is progesterone. In fact, uterine skin graft survival and susceptibility to bacterial infections are increased by progesterone. This review focuses on the role of progesterone in regulation of uterine immune function in the sheep. While the importance of progesterone as a regulator of immune function likely varies between species, concepts derived from the sheep model may prove pertinent to other species also. The actions of progesterone on uterine immune function in the ewe change during pregnancy. Before day 50 of gestation, i.e. when the uterus is still dependent upon the corpus luteum as a source of progesterone, concentrations of progesterone are probably not high enough at the maternal fetal interface to inhibit lymphocyte activation. During this early period of pregnancy, progesterone inhibits uterine immune function by inducing endometrial secretion of a protein called uterine milk protein (UTMP) that itself is inhibitory to lymphocyte function. After day 50 of pregnancy, it is likely that the placenta produces sufficient amounts of progesterone to directly inhibit lymphocyte proliferation. Additional inhibition is achieved because of sustained synthesis of UTMP. Accordingly, progesterone acts to regulate uterine immune function in ways that allows for inhibition of immune responses at the utero-placental interface without systemic immunosuppression.

Animals↗
PubMed2000

Onapristone (ZK299) blocks the suppressive effect of progesterone, but not that of dexamethasone, on inducible nitric oxide synthase gene expression and nitric oxide production in murine macrophages.

Suppressive effects of progesterone on inducible nitric oxide synthase (iNOS) protein expression and nitric oxide (NO) production in murine peritoneal macrophages in response to bacterial lipopolysaccharide (LPS) and the inhibition of the suppressive activity of progesterone by onapristone (ZK299), a synthetic progesterone inhibitor, were studied. Progesterone suppressed dose-dependently LPS-induced NO production by macrophages, and scarcely detectable expression of iNOS was seen in the macrophages. ZK299 liberated the macrophages from the inhibitory effect of progesterone. Although dexamethasone, a synthetic glucocorticoid, can potently suppress LPS-induced NO production by macrophages, ZK299 did not liberate the suppression by dexamethasone, suggesting that these two corticosteroids induce suppression through independent mechanisms. RT-PCR analysis showed that murine macrophages expressed no progesterone-receptor. These findings indicate that the inhibitory effect of progesterone occurs at least on the level of iNOS protein expression in the signaling pathway after the LPS-stimulus. Furthermore, our present data may suggest the existence of a yet unknown type of progesterone-receptor in murine macrophages, the binding to which is responsible for the inhibitory effect of progesterone, or that progesterone may act non-specifically on the macrophages without involvement of any receptor.

Animals↗
PubMed2004

Elevated levels of some neuroactive progesterone metabolites, particularly isopregnanolone, in women with chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a controversial entity whose cause is unknown. In this study we have explored the possibility that progesterone metabolites may be involved. Plasma levels of the progesterone precursor pregnenolone, progesterone itself, and five ring A-reduced metabolites of progesterone were measured in 20 women with CFS and in 13 age-matched controls. To minimize the contribution of the ovary, women were either post-menopausal or in the follicular phase of the menstrual cycle (day 4-8), and progesterone levels were all well within the expected range (< or = 3.5 nmol/l). Mean values for progesterone and all of its metabolites were higher in CFS patients, the most marked being a 2.3-fold elevation in isopregnanolone (3beta,5alpha-tetrahydroprogesterone; p < or = 0.001). Progesterone levels were correlated with those of its metabolites, but even after controlling for progesterone by ANCOVA, isopregnanolone levels were still elevated (p < or = 0.001). These elevated levels of isopregnanolone could not be attributed to medications (antidepressants and anxiolytics). When the CFS patients were divided into two groups according to their Hamilton depression scale ratings, mean (+/-SD) isopregnanolone levels were higher (274+/-160 vs 197+/-119 pmol/l) in the less depressed group (ratings 2-14) than in the more depressed group (ratings 17-28), although this difference did not reach significance. Progesterone levels were negatively correlated with Hamilton depression rating scores (r=-0.56; p<0.01). These results suggest that increases in ring A-reduced progesterone metabolites, particularly isopregnanolone, are associated with CFS, and that the pathophysiology of CFS is unlikely to be due to depression.

Adult↗
PubMed1998

Differential effects of dexamethasone and RU 486, an antigestagen and antiglucocorticoid, on progesterone and relaxin secretion in hysterectomized pigs with aging corpora lutea.

Pregnancy lasts about 114 days in pigs. Porcine corpora lutea produce not only progesterone but also relaxin (RLX), a peptide hormone that plays a critical role in suppressing uterine motility during pregnancy and in remodelling connective tissues in preparation for imminent parturition. Progesterone concentrations in peripheral blood remain elevated (approximately equal to 25 ng ml-1) for the major part of pregnancy and decrease just before parturition. The decrease in progesterone coincides with the peak prepartum RLX release. Glucocorticoid or antiglucocorticosteroid steroid, RU 486, administration during late pregnancy can induce parturition in the pig. Peak release of RLX and a coincident decrease of progesterone in the circulating blood can also occur in the complete absence of fetuses and uterus in the pig. The effects of glucocorticoid or antiglucocorticoidsteroid administration to such hysterectomized pigs on the secretion of RLX and progesterone were examined in this experiment. Unmated Yorkshire gilts were hysterectomized on days 6-8 (estrus = day 0) and given dexamethasone (total of 30 mg day-1; 2 times i.m. at 0800 and 1600 h) from days 110-118; control animals received vehicle injection during this period. RU 486 (4 mg kg1 body weight) was orally administered once daily (days 111-115) at 0800 h; placebo-treated controls were given the same amount of feed without the drug at this time. RLX concentrations in blood were markedly suppressed (P < 0.01) during dexamethasone treatment (3 +/- 0.9 ng ml-1; mean +/- S.E.) whereas a peak release of RLX (17 +/- 2.8 ng ml-1) occurred in the control group on day 113. In contrast, progesterone concentrations (14 +/- 2.5 ng ml-1) were unaffected by dexamethasone treatment compared with the controls (15 +/- 2.0 ng ml-1; P > 0.82). Upon withdrawal of dexamethasone on day 118, RLX plasma concentrations began to increase and peaked at 14 +/- 2.1 ng ml-1 (P < 0.01) on day 120. In contrast, the antiglucocorticosteroid given to hysterectomized pigs bearing aging corpora lutea caused a marked elevation in circulating levels of progesterone and delayed RLX release until after the end of drug treatment on day 115. Average weights of corpora lutea collected at day 12 were similar between treated and control groups (427 +/- 7 vs. 433 +/- 6 mg; P > 0.68). Results indicate that a synthetic glucocorticoid, dexamethasone, suppresses RLX secretion without causing luteolysis and such suppression is reversible; progesterone secretion remained unaffected. In contrast, the antiglucocorticoid, RU 486, raised progesterone plasma concentration and delayed RLX peak release but did not suppress it during treatment. This experiment provides further evidence that relaxin and progesterone secretion from aging corpora lutea of pigs are regulated through separate mechanisms, and adrenal glucocorticoids may be involved in such a regulation process.

Animals↗
PubMedDate not supplied

Progesterone metabolism in human saliva in vitro.

Human salivary glands are known to be able to metabolize progesterone as well as other steroid hormones. The rate of progesterone metabolism in the salivary glands is so low that it is not thought to affect salivary progesterone concentrations. On the other hand it is usually recommended that saliva should be frozen quickly after the collection to prevent any kind of metabolism in saliva. When saliva is collected at home e.g. delayed freezing or partial thawing during to transport to laboratory may create circumstances where progesterone metabolism may occur. However, it is not known to which extent progesterone metabolism continues in saliva and whether this continued metabolism of progesterone affects salivary hormone levels. Paraffin-stimulated salivary samples were collected from female (N = 6) and male (N = 6) dental students and perimenopausal women (N = 8). The salivary samples were incubated with 14C-progesterone for 2 h at 37 degrees C in a shaking water bath. Metabolites were analyzed using thin-layer chromatography and autoradiography and quantified by liquid scintillation counting. Human saliva was found to be able to metabolize progesterone, but its metabolic activity was very low, 9.3 and 6.8 pmol/ml/h in young adults and perimenopausal women, respectively. Metabolic activity was higher in whole saliva than in the corresponding activities of the supernatant or sonicated fraction of the same saliva. The supernatant fraction, which was thought to be mainly representative of glandular saliva, was metabolically least active. The polar metabolites of progesterone predominated in all incubations. The metabolic activity of saliva is probably mainly due to its cellular content and the contribution of this activity to salivary progesterone concentrations is not significant.

Adult↗
PubMedDate not supplied

Progesterone metabolism in human fibroblasts is independent of P-glycoprotein levels and Niemann-Pick type C disease.

Progesterone inhibits intracellular transport of lysosomal cholesterol in cultured cells, and thus at least in part mimics the biochemical phenotype of Niemann-Pick type C disease (NPC) in human fibroblasts. The goal of this study was to determine whether metabolism of progesterone to other steroids is affected by the NPC mutation or by P-glycoprotein (a known progesterone target). We found that human fibroblasts metabolize progesterone in three steps: rapid conversion to 5alpha-pregnane-3,20-dione, which is then reduced to 5alpha-pregnane-3beta(alpha)-ol-20-one with subsequent 6alpha-hydroxylation. The pattern and rates of progesterone metabolism were not significantly different in a variety of fibroblasts from normal individuals, NPC patients, and obligate heterozygotes. Inhibition of steroid 5alpha-reductase with finasteride completely blocked metabolism of progesterone but had no effect on inhibition of LDL-stimulated cholesterol esterification (IC50 = 10 microM). Progesterone also partially inhibited 25-hydroxycholesterol-induced cholesterol esterification, with similar dose-dependence in normal and NPC fibroblasts. P-glycoprotein levels varied significantly among the various fibroblasts tested, but no correlation with NPC phenotype or rate of progesterone metabolism was noted, and P-glycoprotein inhibitors did not affect conversion of progesterone to products. These results indicate that metabolism of progesterone in human fibroblasts is largely independent of its ability to interfere with cholesterol traffic and P-glycoprotein function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Interrelationships among plasma progesterone concentrations, luteal anatomy and function, and placental ontogeny during gestation in a viviparous lizard (Niveoscincus metallicus: Scincidae).

Plasma progesterone concentrations were measured at six stages of gestation in the viviparous lizard Niveoscincus metallicus. Anatomical and functional parameters of luteal activity were also investigated. The diameter of the corpus luteum (CL) decreased gradually though gestation, as did the diameter of the luteal cells. Major degenerative changes were observed in CLs post-partum. Plasma progesterone concentrations were basal both prior to, and just after, ovulation; a rapid increase occurred in early gestation. Plasma progesterone concentrations remained elevated until late gestation, but fell some 2 weeks before parturition. In vitro production of progesterone was greater in CLs in mid- than in late-gestation, and the addition of prostaglandin F(2alpha) to the incubation medium had no effect on progesterone production. Non-luteal ovarian tissue and adrenals produced progesterone, but at approximately one-tenth the rate of production by CLs. Temporal correlations between the plasma progesterone profile and stages of placental development were also assessed. The rise in plasma progesterone concentrations occurs before differentiation of the chorioallantoic placenta, but progesterone is still high when it degenerates. We conclude that the CLs are the major source of gestational progesterone in N. metallicus.

Adrenal Glands↗
PubMed1999

The progesterone blockade of the luteinizing hormone surge is overcome by RU486.

Progesterone can prevent the oestrogen-induced and spontaneous preovulatory luteinizing hormone (LH) surges but the mechanisms underlying this effect remain poorly understood. Using a follicular phase ovariectomised (OVX) ewe model and by elevating progesterone in the presence of oestrogen to inhibit the LH surge, we investigated whether the progesterone receptor antagonist, RU486, could block the inhibitory effects of progesterone. Accordingly, intravaginal progesterone implants were inserted into OVX Ile-de-France ewes (n = 18), bearing 10 mm Silastic 17beta-oestradiol implants. Ten days later, the progesterone implants were removed, whereupon new implants were inserted immediately into 12 ewes: six of which were also injected with 100 mg RU486 dissolved in 10 mL vehicle (10% alcohol in peanut oil) and six received vehicle only. The remaining six ewes were injected with vehicle only. RU486 and vehicle injections were made again 12 and 24 h later. After the last injection, oestrogen concentrations were raised to peak follicular phase levels in all ewes by subcutaneous insertion of four 3-cm 17beta-oestradiol implants. Blood samples were collected every 2 h for 40 h starting 9 h after the insertion of the oestrogen implants. As expected, the six ewes treated only with oestradiol had a LH surge whereas no ewes given the implants in the presence of progesterone surged. RU486 completely blocked the inhibitory effect of progesterone. There were no differences in the time of LH surge onset, duration over which LH levels remained above their half-maximal concentration or magnitude of the LH surge between the two groups showing surges. Our study suggests strongly that the progesterone-mediated blockade of the ovine oestrogen-induced LH surge is not through allopregnanolone activation of the GABA(A) receptor. Rather, our study demonstrates that this effect is transduced by the classic nuclear progesterone receptor.

Administration, Intravaginal↗
PubMed2002

Overexpression of mdm2 and p53 and association with progesterone receptor expression in benign meningiomas.

The progesterone receptor is frequently found expressed in meningiomas at robust levels. As several studies of breast and endometrial tumors have shown an inverse correlation between progesterone receptor expression and p53 overexpression, we sought to determine if a similar relationship existed in meningiomas. As p53 may also be inactivated by the overexpression of mdm2, we examined a cohort of 90 benign meningiomas immunohistochemically for the presence of the progesterone receptor as well as overexpression of p53 and mdm2. The progesterone receptor was detected in 67% (61/90) of cases, while p53 and mdm2 overexpression were detected in 14% (13/90) and 46% (42/90) of cases, respectively. An absolute correlation was observed between the overexpression of nuclear mdm2 and overexpression of the progesterone receptor, with nuclear mdm2 overexpression being confined to progesterone receptor-positive tumors (P = 0.001). While p53 overexpression was not associated with progesterone receptor expression, a combination of mdm2 overexpression and/or p53 overexpression was significantly associated with the presence of the progesterone receptor (P = 0.025). These results suggest the existence of a novel relationship between p53 (and its regulatory control) and the presence of the progesterone receptor and, as such, may have fundamental consequences in developing progesterone receptor-targeted therapies for meningiomas.

Adult↗
PubMed2001

Fetoplacental growth in sheep administered progesterone during the first three days of pregnancy.

We have previously shown that administration of progesterone during early pregnancy in sheep enhances fetal weight and crown-rump length. The present study examined the effect of this treatment on individual fetal organ weights and on placental growth and structure. Embryos that had been exposed to either a normal or a high concentration of progesterone on days 1-3 in initial recipient ewes were transferred at random to final recipient ewes that had or had not been treated with progesterone on days 1-3. Embryos in an additional group of ewes were exposed to progesterone on days 1-3 with oviducts of the ewes ligated. An increase in fetal weight was observed in the final recipient group that had been treated with progesterone (P< 0.01) but not in the initial group treated with progesterone. Fetal weight was increased (P< 0.05) in the initial recipients treated with progesterone plus ligation. Placental weight did not differ between any of the treatments in either initial or final recipients, while placental volumes of chorionic membrane and maternal crypts were increased by progesterone, with and without ligation, in initial recipients (P< 0.05). The responses of fetal weight in final recipients were associated with increases in the weight and linear dimensions of specific fetal components (e.g. brain, kidney, heart, spleen, total gut, head width, thorax circumference). Proportionate increases were observed for most parameters with the exception of brain, heart and M tibialis anterior weight; adjusted least squares means indicated disproportionate increases in these of 5 per cent, 32 per cent and 26 per cent respectively. Enhanced fetal weight in the progesterone plus ligation group was associated with increased (P< 0.05) heart weight; a disproportionate increase of 39 per cent was recorded. Increased fetal weight and fetal heart, skeletal muscle and brain weight were correlated with increased volumes and surface area of the fetal trophectoderm and maternal fetomaternal syncytium in the final recipients treated with progesterone. It is concluded that alteration of the embryo's environment during the first few days of development enhances fetal growth disproportionately, in close association with increased abundance of the exchange epithelia in the placenta.

Animals↗
PubMed1997

Effects of progesterone withdrawal on uterine secretion of prostaglandin F2 alpha in response to oxytocin in ewes.

Two experiments were conducted to determine if withdrawal of progesterone during the luteal phase of the oestrous cycle affected the ability of the ovine uterus to secrete prostaglandin F2 alpha (PGF2 alpha) in response to oxytocin. In Experiment 1, 18 ewes were ovariectomized on Day 9 and Day 12 after oestrus. Ewes were subdivided into three treatment groups (n = 6 per group): Group-1 ewes underwent sham surgery; Group-2 ewes received oestradiol (OVX + O); and Group-3 ewes received oestradiol + progesterone (OVX + O,P). Oxytocin was administered to each ewe on Days 10, 13 and 15 after oestrus. Concentrations of 13, 14-dihydro-15-keto-PGF2 alpha (PGFM) were determined in samples of jugular venous blood for 2 h after oxytocin challenge. The magnitude of the PGFM response 24 h after ovariectomy was greater (P < 0.1) in ewes from which progesterone had been withdrawn (OVX + O) than in ewes in which progesterone was maintained (intact controls and OVX + O,P). Therefore, progesterone appears to exert an inhibitory effect on uterine secretory responsiveness to oxytocin which is removed by progesterone withdrawal. In Experiment 2, ewes were ovariectomized on Day 11 and assigned to 1 of 4 treatment groups (n = 6 per group): Group 1, no steroid replacement (OVX); Group 2, oestradiol replacement (OVX + O); Group 3, progesterone replacement (OVX + P); or Group 4, progesterone + oestradiol replacement (OVX + O,P). Ewes received oxytocin on Day 12 and Day 15. On Day 12, uterine secretory responsiveness to oxytocin was greatest in ewes in the OVX + O group (P < 0.1). Responsiveness was low in ewes in the OVX group, as it was in ewes in both groups that received progesterone replacement. Therefore, the increase in uterine secretory responsiveness to oxytocin following progesterone withdrawal is dependent on oestradiol replacement.

Animals↗