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PubMed2000

Tissue-specific regulation of gastrin-releasing peptide synthesis, storage and secretion by oestrogen and progesterone.

In the ovine endometrium, dramatic increases in gastrin-releasing peptide (GRP) mRNA and immunoreactivity are observed during the luteal regression phase of the oestrous cycle (24-fold) and during pregnancy (at least 150-fold). This study sought to determine whether oestrogen and/or progesterone were responsible for the temporal regulation of GRP observed in the uterus. Ovariectomized sheep were divided into four groups (n=4), as follows: 1, untreated; 2, given subcutaneous and intravaginal progesterone implants; 3, given subcutaneous oestrogen implants; and 4, treated with both oestrogen and progesterone. After 10 days, the animals were sacrificed and plasma, pituitary and endometrium were obtained. A fifth group of sheep with intact ovaries was included. Analysis of endometrial GRP-immunoreactivity (GRP-ir) revealed a twofold drop for groups treated with oestrogen, progesterone or both hormones. A dramatic reduction in endometrial GRP mRNA was o! bserved in the group treated with both hormones. GRP-ir was measured in whole pituitaries and found to vary greatly (1.7-53.7 pmol/g tissue) within all groups of ovariectomized animals. There were no significant differences between any of the five groups. A significant reduction in circulating GRP-ir was observed after 10 days of treatment with either oestrogen or progesterone. These studies demonstrate that, in sheep, the synthesis, storage and secretion of GRP are differentially affected by oestrogen and progesterone. Regulation appears to be tissue specific since GRP content in the pituitary is unchanged by oestrogen or progesterone whereas GRP expression in the endometrium is inhibited. Changes in GRP mRNA expression did not correlate with changes in endometrial expression of mRNA for oestrogen receptor alpha, oestrogen receptor beta and the progesterone receptor. This study is the first reported demonstration that expression of the GRP gene can be influenced by the presence of ovarian steroids, with the conclusion that oestrogen and/or progesterone act as negative regulators of endometrial GRP expression.

Actins↗
PubMed2001

Progesterone and testosterone in combination act in the hypothalamus of castrated rams to regulate the secretion of LH.

We tested the hypotheses that progesterone enhances the negative feedback actions of testosterone in rams and that this occurs through actions at the hypothalamus. In the first part of this study, blood samples were collected every 10 min for 12 h before and after 7 days of treatment (i.m.) of castrated Romney Marsh rams (n=5 per group) with vehicle, progesterone (4 mg/12 h), testosterone (4 mg/12 h) or a combination of progesterone (4 mg/12 h) and testosterone (4 mg/12 h). In the second part of this study the brains of four gonad-intact Romney Marsh rams were collected, the hypothalamus was sectioned and in situ hybridisation of mRNA for progesterone receptors conducted. After 7 days of treatment with vehicle or progesterone or testosterone alone, there were no changes in the secretion of LH. In contrast, treatment with a combination of progesterone and testosterone resulted in a significant (P<0.01, repeated measures ANOVA) decrease in mean plasma concentrations of LH, the number of LH pulses per hour and the pre-LH pulse nadir and a significant (P<0.01) increase in the inter-LH pulse interval. We found cells containing mRNA for progesterone receptors throughout the hypothalamus, including the preoptic area (where most GnRH neurons are located in sheep), the periventricular, ventromedial and arcuate nuclei and the bed nucleus of the stria terminalis. This study shows that progesterone is capable of acting centrally with testosterone to suppress the secretion of LH in castrated rams and that cells containing mRNA for progesterone receptors are located in the hypothalamus of rams in the vicinity of GnRH neurons.

Analysis of Variance↗
PubMed1993

[Expression of progesterone-binding protein in normal and neoplastic human adrenals].

Specific progesterone-binding protein (P4-BP) is demonstrated in adrenocortical nuclei of the guinea pig, but, not in nuclei of other animals. We tried to demonstrate the progesterone-binding activity in nuclei of human normal adrenals and adrenal tumors. Normal adrenals were obtained from six patients with renal cell carcinomas undergoing radical nephrectomy. Seven adrenocortical adenomas were obtained: five tumors from patients with Cushing's syndrome, one tumor from non-functioning adenoma, and one from aldosteronoma. Nuclei were purified from the tissues, and progesterone binding assay was performed. We could not demonstrated progesterone-binding activity in nuclei of six normal human adrenals. However, we demonstrated progesterone-binding activity in nuclei purified from human adrenocortical adenomas associated with Cushing's syndrome. Saturation analysis revealed a Kd of 13.85 +/- 1.99 nM (mean +/- SD, n = 5) and a binding capacity of 1.95 +/- 0.37 pmol/mg DNA (mean +/- SD, n = 5). A Kd of progesterone-binding activity in human adrenocortical adenoma was similar to that of guinea pig P4-BP, and a binding capacity was about one-fifteenth of guinea pig P4-BP. However, nuclei purified from a non-functioning adrenocortical adenoma and an aldosteronoma failed to demonstrate progesterone-binding activity. The binding activity was specific for progesterone. 5 alpha-pregnane-3,20-dione was a modest competitor, while 17 beta-estradiol, testosterone, cortisol, and other related steroids were poor competitors. Thus the progesterone-binding activity in human adrenals was similar to guinea pig P4-BP in the affinity and specificity of binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMedDate not supplied

Effect of mifepristone on steroid receptor expression and biotransformation of oestrogen and progesterone in rat uterus and deciduoma.

BACKGROUND: [corrected] Mifepristone is a synthetic antiprogestin which terminates early pregnancy. Since it interferes with the progesterone maintained decidua, we compared the effect of mifepristone on oestrogen and progesterone receptors, and on the biotransformation of these hormones in normal and deciduous uterus. METHODS: Ovariectomized rats were treated with an oestrogen-progesterone hormone regimen and deciduoma was induced by trauma in one horn of the rat uterus while the other served as a control under an identical hormonal milieu. Hormone receptor and biotransformation studies were done using radiolabelled oestradiol and progesterone with high specific activity. RESULTS: The artificially formed decidual tissue was comparable with that of early pregnancy. Mifepristone replenished oestrogen and progesterone receptors which were suppressed by progesterone in both the normal and decidualized uterine horns. Inhibition of oestrogen receptors by progesterone correlated with decreased oestradiol levels at the site of action. Metabolism of progesterone to less potent compounds was promoted by mifepristone. The enzymatic activities of 17beta-hydroxysteroid dehydrogenase (which metabolizes oestradiol), and 20alpha-hydroxysteroid dehydrogenase and 5alpha-reductase (which metabolize progesterone) were altered by mifepristone. CONCLUSION: The effect of mifepristone in varying the hormone receptor population and the availability of different levels of active metabolites of ovarian hormones have an Important role in the antiprogestin action of mifepristone.

Abortifacient Agents, Steroidal↗
PubMedDate not supplied

[Reception of progesterone and its biological action in the uterus of neonatally androgenized rats].

The relationship of the level of uterine progesterone receptors and plasma concentration of female sex steroids with the biological effect of progesterone (its effect on collagen content and the number of uterine endometrial glands) was studied in neonatally androgenized female rats aged 90-120 days. In these animals the level of progesterone receptors in the uterine cytosol fraction was raised, in the nuclear fraction it was lowered. Plasma concentration values of estradiol and progesterone in such animals did not differ from those of intact female rats. The ability of estradiol to induce the synthesis of uterine progesterone receptors was less noticeable in androgen sterile animals. The sensitivity of the uterus to progesterone in such animals was lowered either. Progesterone doses causing a significant decrease in the concentration of progesterone receptors in cytosol and in uterine tissue collagen content, proved to be ineffective for androgen sterile female rats. Disturbance of progesterone reception and a related decrease in the sensitivity of the uterus of androgen sterile animals to this hormone can be probably determined by an irreversible androgen effect on the target cell genome in the early neonatal period, not depending on the peculiarities of hormonal regulation in adult rats.

Animals↗
PubMed1996

Unusual steroid specificity of the cell surface progesterone receptor on human sperm.

The steroid specificity of the cell surface progesterone receptor in human sperm was examined with the use of progesterone, testosterone, and androstane analogues. Many compounds were shown to be more effective than progesterone at increasing intracellular free calcium concentration, e.g., 2 alpha-methyl-17beta-methoxy-5 alpha-androstan-3-one. Several testosterone analogues were demonstrated to be antagonists of progesterone, e.g., 9(11)-dehydro-2 alpha,17alpha-dimethyltestosterone. The synthetic potent progestigens, norethynodrel, cyproterone acetate, norethindrone, and megestrol acetate, were found to be only weak stimulators of the sperm cell surface receptor. Furthermore, these compounds were shown to antagonize the effect of progesterone to elevate intracellular free calcium concentration in sperm. It is known that progesterone and some of its analogues bind to the intracellular progesterone nuclear receptor via the alpha-face of the steroid molecule. In stark contrast, it was concluded from the analysis of the steroid analogues examined on human sperm in this study that intimate contact exists between the effective progesterone analogues and the sperm cell surface progesterone receptor across the beta-face of the steroid C/D-ring "upper" edge (C11, C12, and C17). Positioning of the C21 methyl group is also critical for efficacy, and recognition of the steroid A-ring seems not to be involved.

Dose-Response Relationship, Drug↗
PubMed1998

In vitro effect of estradiol, progesterone, testosterone, and of combined estradiol/progestins on low density lipoprotein (LDL) oxidation in postmenopausal women.

OBJECTIVE: One of the mechanisms currently proposed to explain the cardioprotective effect of hormone replacement therapy (HRT) is the antioxidative property of estrogens. Considering that HRT involves the administration of an estrogen, usually combined with a progestin and sometimes with an androgen, we investigated the following in vitro: (1) the effect of estradiol, progesterone, and testosterone on the oxidation of low density lipoprotein; (2) the possible pro-oxidative effect of progesterone and testosterone on native low density lipoprotein; and (3) the possible modification of the antioxidant effect of estradiol on low density lipoprotein induced by progestins. DESIGN: Low density lipoprotein was isolated from blood samples obtained from 20 untreated postmenopausal women and divided in multiple aliquots, each containing 0.5 mg LDL protein. In Protocol 1 (n = 10) different doses of estradiol, progesterone, and testosterone ranging from 0 to 26 micrograms/ml were tested inducing oxidation with 15 microM copper sulfate. In Protocol 2 (n = 6) we studied the rate of oxidation of low density lipoprotein incubated with progesterone or testosterone without any oxidative induction. In Protocol 3 (n = 10) we studied the concomitant effect of 15 microM estradiol with four separate progestins (progesterone, medroxyprogesterone acetate, norethindrone, and norgestrel) in different doses (0, 5, 15, and 50 microM). After incubation for 4 h at 37 degrees C, malonaldehyde was measured as a marker of low density lipoprotein oxidation. The results were expressed in mean +/- SD. RESULTS: Protocol 1: Estradiol induced a dose-dependent decrease in malonaldehyde generation, from a baseline of 61.8 +/- 30.2 nmol/mg protein to 11.6 +/- 7.1 nmol/mg protein at the highest dose of estradiol tested (p < 0.0001). Progesterone or testosterone did not modify malonaldehyde generation. Protocol 2: Progesterone and testosterone did not show pro-oxidative action. Protocol 3: Estradiol 15 microM alone induced a 35% decrease in malonaldehyde generation, from a baseline of 75.4 +/- 25.4 to 49.3 +/- 18.8 nmol/mg protein (p < 0.0001). Norgestrel and norethindrone did not modify the antioxidant effect of estradiol (p > 0.05). Progesterone and medroxyprogesterone acetate induced a further reduction of malonaldehyde concentration to 37.2 +/- 20.8 and 38.6 +/- 18.2 nmol/mg protein, only at the highest dose tested (p < 0.02 and p < 0.01, respectively). CONCLUSIONS: Our results demonstrate that, in contrast with the potent antioxidant effect of estradiol, progesterone and testosterone did not show any pro- or antioxidant effect on low density lipoprotein in vitro. Furthermore, progestins did not counteract the antioxidant effect of estradiol in vitro.

Copper Sulfate↗
PubMed2006

Prenatal administration of progesterone for preventing preterm birth.

BACKGROUND: Preterm birth is the major complication of pregnancy associated with perinatal mortality and morbidity and occurs in up to 6% to 10% of all births. Administration of progesterone for the prevention of preterm labour has been advocated. OBJECTIVES: To assess the benefits and harms of progesterone administration during pregnancy in the prevention of preterm birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Specialised Register of Controlled Trials (March 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2004), MEDLINE (1965 to January 2005), EMBASE (1988 to August 2004), and Current Contents (1997 to August 2004). SELECTION CRITERIA: All published and unpublished randomised controlled trials, in which progesterone was given by any route for preventing preterm birth. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group were used. Evaluation of methodological quality and trial data extraction were undertaken independently by two authors. Results are presented using relative risk with 95% confidence intervals. MAIN RESULTS: For all women administered progesterone, there was a reduction in the risk of preterm birth less than 37 weeks (six studies, 988 participants, relative risk (RR) 0.65, 95% confidence interval (CI) 0.54 to 0.79) and preterm birth less than 34 weeks (one study, 142 participants, RR 0.15, 95% CI 0.04 to 0.64). Infants born to mothers administered progesterone were less likely to have birthweight less than 2500 grams (four studies, 763 infants, RR 0.63, 95% CI 0.49 to 0.81) or intraventricular haemorrhage (one study, 458 infants, RR 0.25, 95% CI 0.08 to 0.82). There was no difference in perinatal death between women administered progesterone and those administered placebo (five studies, 921 participants, RR 0.66, 95% CI 0.37 to 1.19). There were no other differences reported for maternal or neonatal outcomes. AUTHORS' CONCLUSIONS: Intramuscular progesterone is associated with a reduction in the risk of preterm birth less than 37 weeks' gestation, and infant birthweight less than 2500 grams. However, other important maternal and infant outcomes have been poorly reported to date, with most outcomes reported from a single trial only (Meis 2003). It is unclear if the prolongation of gestation translates into improved maternal and longer-term infant health outcomes. Similarly, information regarding the potential harms of progesterone therapy to prevent preterm birth is limited. Further information is required about the use of vaginal progesterone in the prevention of preterm birth.

17-alpha-Hydroxyprogesterone↗
PubMed2006

Progesterone for preventing pre-eclampsia and its complications.

BACKGROUND: In the past, progesterone has been advocated for prevention of pre-eclampsia and its complications. Although progestogens are not used for this purpose in current clinical practice, it remains relevant to assess the evidence on their possible benefits and harms. OBJECTIVES: To assess the effects of progesterone during pregnancy on the risk of developing pre-eclampsia and its complications. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 2), and EMBASE (1974 to August 2005). SELECTION CRITERIA: Randomised trials evaluating progesterone or any other progestogen during pregnancy for prevention of pre-eclampsia and its complications were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and extracted data. MAIN RESULTS: Two trials of uncertain quality were included (296 women). These trials compared progesterone injections with no progesterone. There was insufficient evidence to demonstrate any clear differences between the two groups on the risk of pre-eclampsia (one trial, 128 women; relative risk (RR) 0.21, 95% confidence interval (CI) 0.03 to 1.77), death of the baby (two trials, 296 women; RR 0.72, 95% CI 0.21 to 2.51), preterm birth (one trial, 168 women; RR 1.10, 95% CI 0.33 to 3.66), small-for-gestational-age babies (one trial, 168 women; RR 0.83, 95% CI 0.19 to 3.57) or major congenital defects (one trial, 168 women; RR 1.65, 95% CI 0.28 to 9.62). There were no reported cases of masculinisation of female babies (one trial, 128 women). Long-term follow up for the children has been reported in one trial, but the data are excluded from the review as 54% were lost to follow up at one year and 80% at 16 years. AUTHORS' CONCLUSIONS: There is insufficient evidence for reliable conclusions about the effects of progesterone for preventing pre-eclampsia and its complications. Therefore, progesterone should not be used for this purpose in clinical practice at present. Unless new and plausible hypotheses emerge for the role of progesterone in development of pre-eclampsia, further trials of progesterone are unlikely to be a priority.

Female↗
PubMed1990

Effects of prostaglandin E2 and progesterone on rat brain synaptosomal plasma membranes.

The lipid fluidity of rat brain synaptosomal plasma membranes (SPM) labelled with 1,6-diphenyl-1,3,5-hexatriene (DPH) was increased by prostaglandin E2 (PGE2) and decreased by progesterone, as indicated by steady-state fluorescence anisotropy [(ro/r)-1]-1. Arrhenius-type plots of [(ro/r)-1]-1 indicated a lipid phase separation of SPM at approximately 23.5 degrees C which was reduced to approximately 18.1 degrees C by PGE2 and increased to approximately 34.6 degrees C by progesterone. Treatment of SPM by PGE2 and progesterone caused an increase of the lipid phase separation to approximately 32.4 degrees C. Arrhenius plots of Na+/K(+)-ATPase activity in control SPM exhibited a break point at approximately 23.1 degrees C which was reduced to approximately 17.8 degrees C by PGE2 and increased to approximately 32.6 degrees C by progesterone. SPM treated with PGE2 plus progesterone showed an increased break point at approximately 29.3 degrees C. Na+/K(+)-ATPase activity was increased at a PGE2 concentration range between 0.1 and 3 microM; higher concentrations (up to 10 microM) led to a gradual inhibition of enzyme activity. Progesterone (0.1-10 microM) and PGE2 plus progesterone both produced a gradual decrease in enzyme activity. The allosteric inhibition of Na+/K(+)-ATPase by fluoride (F-) (as reflected by changes in the Hill coefficient) was modulated by PGE2 and progesterone. The perturbations of membrane lipid structure and changes in membrane fluidity provide a basis for suggesting an independent non-genomic mechanism for the progesterone-induced alterations in the effects of PGE2 on brain function.

Animals↗
PubMedDate not supplied

The effect of progesterone on the regulatory mechanisms of biliary cholesterol secretion in the rat.

We tested the hypothesis that progesterone, an inhibitor of cholesterol esterification in liver microsomes, increases biliary cholesterol output by increasing the availability of cholesterol. Initial bile samples of 20 min were obtained from acute bile fistula rats after seven daily doses of progesterone (5 to 55 mg per kg of body weight). Biliary cholesterol output correlated with the doses of progesterone, r = 0.64 (p less than 0.005). A 100% increment in biliary cholesterol output was obtained with progesterone doses of 30 to 55 mg per kg of body weight. Under these conditions, biliary phospholipid output increased 50% (p less than 0.02), but bile salt output remained normal. The relationship between biliary cholesterol and phospholipids as a function of bile salt output was studied after acute depletion of the bile salt pool. A rectangular hyperbola was the best curve fitting for the experimental data in control and progesterone-injected rats. In the physiological range of bile salt output, between 60 and 120 nmoles per gm per min, progesterone-injected rats secreted 100% more biliary cholesterol than did controls. The calculated theoretical maximal cholesterol and phospholipid outputs were significantly increased in progesterone-injected animals. Serum and hepatic cholesterol pool, free and ester fractions, remained normal. The acyl-CoA: cholesterol acyltransferase reaction was 30% inhibited in hepatic microsomes of progesterone-injected rats, (p less than 0.05). The changes in biliary phospholipids and cholesterol output produced by progesterone were rapidly reversed by either 0.5% cholesterol feeding or 2 mg per kg of body weight ethynyl estradiol injection. These manipulations simultaneously produced a 100% increment in the microsomal acyl-CoA: cholesterol acyltransferase activity (p less than 0.005) and increased 4-fold the concentration of hepatic cholesterol esters. This experimental model suggests a functional interrelationship between biliary cholesterol output and the rate at which the liver esterifies cholesterol.

Animals↗
PubMed1997

Several synthetic chemicals inhibit progesterone receptor-mediated transactivation in yeast.

The human progesterone receptor (hPR) B-form and a progesterone-sensitive reporter were expressed in yeast and used to screen a library of synthetic chemicals for their ability to function as agonists or antagonists of hPR. The transcriptional activity of hPR was not increased in the presence of over 40 individual chemicals. Seven chemicals decreased progesterone-dependent activity in yeast. The most effective chemicals were 6-hydroxychrysene, 1-hydroxypyrene, 4-hydroxy, 2',4',6'-trichloro biphenyl, and 4-hydroxy, 2',3',4',5'-tetrachloro biphenyl. The decrease of progesterone-mediated transactivation strongly correlated with their displacement of [3H]progesterone from hPR. The absence of the hydroxyl group on the above chemicals completely abolished their inhibitory activity. The other chemicals which decreased progesterone activity were endosulfan II, endosulfan sulfate, and lindane. These chemicals did not inhibit [3H]progesterone binding, suggesting that they inhibit progesterone action by interacting with a region of hPR distinct from binding [3H]progesterone or by a mechanism independent of hPR. These results highlight the utility of yeast for screening hormonally-active chemicals. In addition, hydroxylation appears to be essential for the interaction of some chemicals with hPR.

Humans↗
PubMed1993

Evidence suggesting involvement of a unique human sperm steroid receptor/Cl- channel complex in the progesterone-initiated acrosome reaction.

Progesterone (4-pregnen-3-20-dione) initiates the acrosome reaction (AR) of human sperm in vitro. Anesthetic progestins (e.g., progesterone) potentiate gamma-aminobutyric acid (GABA) activation of neuronal GABAA receptor/Cl- channel complexes (GBRCs), and some can activate neuronal GBRCs in the absence of GABA. Here, we study whether human sperm acrosome reaction initiation by progesterone and several other progestins involves steroid interaction with a sperm GBRC. Anesthetically active 3 alpha-OH isomers of two progesterone metabolites, as well as the synthetic 3 alpha-OH anesthetic steroid Alphaxalone, their 3 beta-OH isomers (inactive as anesthetics), or progesterone, were added to capacitated human sperm. The 3 alpha-OH isomers initiated the AR, and the 3 beta-OH isomers were without effect. Moreover, the 3 alpha-OH isomers were less effective than progesterone, a progestin that does not activate neuronal GBRCs in the absence of GABA. Also, alphaxalone, a very potent activator of neuronal GBRCs, was the least active of the progestins tested. GABA was not detected in human sperm. Preincubation of capacitated sperm with GBRC Cl- channel blockers dramatically reduced the progesterone-initiated AR, and sperm were unable to undergo the progesterone-initiated AR in Cl(-)-deficient medium. AR initiation by the calcium ionophore ionomycin was not inhibited in Cl(-)-deficient medium or by GBRC Cl- channel blockers. Indirect immunofluorescence, using a monoclonal antibody to the bovine cerebral cortex GABAA receptor alpha-subunit, localized immunoreactivity in live and fixed sperm as a fluorescent band in the sperm plasma membrane overlying or near the narrow equatorial segment region of the acrosome. Immunoblotting using this antibody detected two major bands with apparent molecular weights of 50 kDa (as reported in other cell types) and 75 kDa (not reported in other cells). Our data suggest that (1) progesterone exerts its effect on capacitated human sperm at least partially by interaction with a unique sperm steroid receptor/Cl- channel complex resembling a neuronal GBRC but apparently possessing a different sensitivity to progestins; and that (2) this interaction results in an increased Cl- flux essential to AR initiation.

Acrosome↗
PubMed1997

Regulation of human papillomavirus type 18 in vivo: effects of estrogen and progesterone in transgenic mice.

We examined the in vivo effect of estrogen, progesterone, RU 486, and pregnancy on the upstream regulatory region (URR) of human papillomavirus (HPV) 18 transgenic mice. The mice contain the bacterial reporter beta-galactosidase gene under control of the HPV 18 URR. Pregnant transgenic mice were sacrificed on various days of gestation and the level of URR activation was determined. Another group of female transgenic mice was ovariectomized at 4 to 6 weeks of age. Pellets of estradiol, progesterone, progesterone + RU 486, or placebo were implanted 1 to 2 weeks after ovariectomy. Mice were sacrificed after pellet implantation to examine acute and chronic effects. Marked increases in URR activation during pregnancy were observed. Progesterone was found to activate the URR acutely. Significantly higher activation was demonstrated at 24 hr in the progesterone group compared to placebo (P < 0.01). Activation with progesterone at 24 hr was significantly higher than at any other time point (P < 0.001). A trend toward decreasing activation over time was demonstrated in the progesterone group (r = -0.87, P = 0.0001). RU 486 does not block the activation of progesterone in our model. Estradiol activates the URR acutely compared to placebo (P = 0.034). This in vivo model demonstrates activation of the URR in response to exogenous estrogen, progesterone, and pregnancy. These data may have clinical implications for women who harbor high-risk HPV.

Animals↗
PubMed1996

Allopregnanolone (THP) mediates anesthetic effects of progesterone in rat brain.

Intravenous infusion of the progesterone or that of progesterone 5 alpha-reduced metabolite, 3 alpha-hydroxy-5 alpha-pregnan-20-one (THP), induces the loss of righting reflex in freely moving rats at the doses of 49 +/- 15 mg/kg or 5.6 +/- 2.2 mg/kg, respectively. The recovery time of righting reflex was 71 +/- 12 min and 21 +/- 5 min for progesterone and THP, respectively. The time course of brain concentrations of THP, but not that of progesterone, correlated with the loss and the recovery of righting reflex. The pretreatment of animals with uncompetitive inhibitor of 5 alpha-reductase 17 beta (N,N-diisopropylcarbamoyl)-androst-3-diene-3-carboxylic acid (SKF 105111) significantly reduces the anesthetic activity of progesterone, but not that of THP. Following progesterone infusion brain level of THP in SKF 105111 pretreated rats was 12% that of vehicle-treated control, and the level of progesterone was 160%. No effect of SKF 105111 on brain THP level was detected in animals infused with THP. These results demonstrate that anesthetic effect of progesterone is mediated through its conversion to THP and support the hypothesis that endogenous metabolites of progesterone may be involved in the regulation of behavior in rats.

Anesthetics↗
PubMed2000

Progesterone inhibits female courtship behavior in domestic canaries (Serinus canaria).

We studied copulation solicitation display (CSD) responses to playback in photostimulated female canaries given systemic injections of progesterone. Eight females received injections of 0.1 mg of progesterone dissolved in olive oil during their first breeding cycle and were untreated during their second breeding cycle; eight females received only the oil vehicle during their first breeding cycle and received no treatment during their second breeding cycle. The injections were performed every second day during 15 days, after the onset of nest building. Progesterone treatment resulted in a significant increase of plasma progesterone which in turn provoked an inhibition of females' CSDs and decreased the size of the clutch. During the first breeding cycle, progesterone-treated females had lower CSDs and egg-laying scores than did control females. During the second breeding cycle, when females received no treatment, no differences emerged between the two groups. The suppressive effect of progesterone on female sexual responses was observed as soon as 48 h after the beginning of the treatment. We propose that progesterone plays a key role in mediating the transition from active female courtship behavior to sexual refractoriness in this species. Suppressive effects of progesterone on female sexual behavior have been previously described in lizards as well as in rodents. Our data are consistent with the hypothesis of Godwin et al. (J. Godwin, V. Hartman, M. Grammer, and D. Crews, Horm. Behav. 30, 138-144, 1996) which proposed that the decrease in sexual behavior following plasma progesterone increase represents an evolutionarily conserved mechanism in the regulation of female sexual behavior.

Animals↗
PubMed1995

Progesterone concentration as a predictor of pregnancy normalcy is the most useful when hCG levels are less than 2000 mIU/mL.

OBJECTIVE: Measurements of serum progesterone to predict early gestational normalcy have been found to be as predictive as serial hCG titers. Since ultrasound would be the diagnostic tool of choice if hCG was > 2000 mIU/ml, the purpose of the present study was to determine the best predictive value of a single progesterone measurement when hCG levels were < 2000 mIU/ml. DESIGN: Relative operating characteristic analysis of progesterone level as a predictor of early gestational normalcy when hCG is < 2000 mIU/ml. MATERIALS AND METHODS: Ninety-three pregnant patients that conceived spontaneously were evaluated with progesterone measurements when the patient's hCG was < 2000 mIU/ml. Two-by-two contingency tables were constructed that compared pregnancy outcome with multiple discriminatory serum progesterone concentrations between 0 and 38 ng/mL. From these tables, a relative operating characteristic (ROC) curve was generated to compare the sensitivity and false-positive rates. RESULTS: Of a total of 93 pregnancies, 27 had a normal outcome and 66 had an abnormal outcome. The ROC curve indicated that a serum progesterone concentration of 12 ng/ml had the highest sensitivity associated with the lowest false-positive rate. The area under the curve was equal to 0.941 +/- 0.024. This observation was compared to our previously reported data of progesterone levels that included hCG levels > 2000 mIU/ml, yielding an area under the curve of 0.772 +/- 0.053. Calculation of the critical ratio z revealed that there is a significant improvement in the predictive value of progesterone when hCG is < 2000 mIU/ml (P < 0.005). CONCLUSION: A single serum progesterone level has a better predictive value of pregnancy normalcy when hCG measurements are < 2000 mIU/ml.

Chorionic Gonadotropin↗
PubMed1995

Progesterone co-administration in patients discontinuing long-term benzodiazepine therapy: effects on withdrawal severity and taper outcome.

Since recent research has suggested that the major metabolites of progesterone are barbiturate-like modulators of GABAergic function, we undertook a pilot study of the efficacy of micronized progesterone in attenuating withdrawal and facilitating discontinuation in benzodiazepine-dependent patients with a minimum of 1 year of continuous daily use. Forty-three patients taking a mean daily dose of 16.2 mg of diazepam (or its equivalent) were assigned, doubleblind, to treatment with either placebo (n = 13) or progesterone (n = 30). Progesterone was titrated to a mean daily dose of 1983 mg, and was co-administered for 3 weeks, after which the benzodiazepine was tapered by 25% per week. Progesterone (or placebo) was then continued for 4 weeks before being discontinued. There was no progesterone versus placebo difference in the severity of taper withdrawal. Withdrawal checklist change scores were 17.3 for progesterone and 16.5 for placebo (F 0.63; df 2.31; n.s.), and the Hamilton rating scale for anxiety change scores were 7.8 for progesterone and 6.3 for placebo (F 0.22; df 2.30; n.s.). There was no difference in ability to remain drug-free at 12 weeks post-taper, with 57% of progesterone-treated patients, and 58% of placebo-treated patients having a successful outcome.

Adult↗