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At least 109 records · Page 6Linked to original sources
PubMed1994

Effect of RU486 on ovarian progesterone production at pro-oestrus and during pregnancy: a possible dual regulation of the biosynthesis of progesterone.

Changes in progesterone production were analysed after intrabursal ovarian administration of the antiprogesterone RU486, mifepristone, in rats at pro-oestrus and during pregnancy. RU486 was administered at 09:00-10:00 h and serum progesterone was measured 8 h after treatment, except for those on days 3 and 12 of pregnancy when the steroid was measured 4, 8 and 24 h later. RU486 stimulates progesterone production on the day of pro-oestrus and on days 3-5 and 15-20 of pregnancy. Conversely, treatment with the antiprogestagen inhibits progesterone production on days 7-14 of gestation. The inhibition (day 12) or stimulation (day 19) of progesterone production induced by RU486 could be correlated with the simultaneous inhibition or stimulation of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity observed in corpora lutea. A similar effect on 3 beta-HSD activity in corpora lutea was obtained by intrabursal ovarian administration of a specific progesterone antibody, indicating that the effect of RU486 is exerted through its antiprogesterone action. On the day of pro-oestrus and during early pregnancy the intrabursal ovarian injection of RU486 did not modify serum prolactin and LH concentrations, demonstrating that the antiprogesterone did not have a central action. The stimulatory action of RU486 on progesterone production on days 3 and 5 of pregnancy shifted to an inhibitory effect on progesterone production on day 7. Oestradiol treatment on day 6 of pregnancy reversed the effect of RU486 on progesterone production on day 7, inducing a response similar to that obtained on days 3 and 5 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

[The use of rapid progesterone tests (Serozyme-Progesterone, Ovucheck) for the diagnosis of pregnancy in Austrian mountain sheep].

To determine the oestrous cycle length of mountain sheep 10 ewes were stimulated with intravaginal sponges (Chronogest) and ten with prostaglandins (Iliren) and a PMSG injection (500 IU), respectively. Independent of the synchronisation mode the Serozyme-progesterone levels indicated a cycle length of 17 days. Progesterone was not detectable by the test system during oestrous, it reached its maximum on the 10th day (mean = 3.9/3.7 ng/ml) and decreased to non-detectable levels again on day 17. For early pregnancy diagnosis the Serozyme-progesterone as well as the Ovucheck gave useful results. On day 17 and 19 after mating the progesterone concentration of pregnant ewes remained on the same level as on day 10, whereas barren ewes had non-detectable progesterone levels on day 17 and 19, using the Serozyme-progesterone and below 1 ng/ml on day 19 using the Ovucheck. The accuracy of the Serozyme-progesterone referring to the declaration "non pregnant" was 100%, that of the Ovucheck 37.5% on day 17 and 100% on day 19. The use of both test systems for determining pregnancy of unknown length was examined by collecting blood-samples three times with a five and a seven day interval. Precise results were obtained only with the Serozyme-progesterone test. At least one of three blood samples of all the barren ewes (n = 8) contained amounts of progesterone beneath the sensitivity of this method. The Ovucheck results could not help at all to distinguish barren or pregnant ewes with unknown mating data.

Animals↗
PubMed1983

Plasma and endometrial progesterone content following exogenous progesterone administration in mares.

Intact and ovariectomized pony mares were treated with either progesterone in-oil or repositol progesterone. Serum progesterone, endometrial progesterone and endometrial histology were examined. There were no differences in serum or tissue progesterone between intact and ovariectomized mares. Serum and tissue progesterone were greater for progesterone in-oil treated mares than for repositol treated mares. Both progesterone in-oil and repositol progesterone initiated endometrial gland proliferation with no difference in response observed between the two preparations.

Journal Article↗
PubMed1996

Progesterone inhibits female-typical receptive behavior and decreases hypothalamic estrogen and progesterone receptor messenger ribonucleic acid levels in whiptail lizards (genus Cnemidophorus).

Female-typical sexual behavior in tetrapods is mediated primarily by estrogen and progesterone acting through intracellular receptors at specific sites in the mediobasal hypothalamus. Progesterone exerts both faciliatory and inhibitory actions on female sexual behavior and in well-studied rodent models, the inhibitory actions are exerted through downregulation of progesterone and estrogen receptors. This study examined progesterone effects on both female-typical sexual behavior and hypothalamic estrogen and progesterone receptor mRNA expression (ER- and PR-mRNA) in a sexual and parthenogenetic species of whiptail lizard. Progesterone capsules administered to ovariectomized female Cnemidophorus inornatus and Cnemidophorus uniparens following a receptivity-inducing dosage of estradiol benzoate (EB) strongly inhibited receptive behavior as compared to blank implanted controls. Progesterone capsules administered either before or after an EB injection also strongly downregulated ER- and PR-mRNA abundance in the ventromedial nucleus of the hypothalamus relative to blank implanted controls. The correlated decrease in both EB-induced receptive behavior and ER- and PR-mRNAs following progesterone administration are similar to findings in rats and guinea pigs, suggesting that this is an evolutionarily conserved mechanism in the regulation of female sexual behavior.

Animals↗
PubMed1987

Modulation of the progesterone receptor in the fetal uterus of the progesterone-primed guinea pig in vivo and in organ culture.

Guinea pig fetuses were treated with progesterone for 7 days before placing fetal uteri in organ culture to see if progesterone pre-treatment of fetuses in utero would permanently inhibit the spontaneous rise in progesterone receptor which occurs in organ culture. The data show that: the basal level of progesterone receptor in fetal uteri was not affected by the progesterone treatment and progesterone receptor concentrations in vitro were also not inhibited. When guinea pig fetuses were treated sequentially with progesterone and estradiol, estradiol failed to provoke an uterotrophic effect but it retained its ability to stimulate progesterone receptor concentrations.

Animals↗
PubMed2001

Formation of pinopodes in human endometrium is associated with the concentrations of progesterone and progesterone receptors.

OBJECTIVE: To investigate the relation between the development of endometrial pinopodes and the serum concentration of hormones and the distribution of estrogen receptor-alpha, estrogen receptor-beta, progesterone receptor A, and progesterone receptor B. DESIGN: Prospective clinical study. SETTING: Hospital-based unit of reproductive health and university-affiliated reproductive research laboratories. PATIENT(S): Twenty-seven healthy fertile women with normal menstrual cycles. INTERVENTION(S): Urine and blood sampling for hormone measurement, vaginal ultrasonography, and endometrial biopsy. MAIN OUTCOME MEASURE(S): Appearance of the endometrium on light microscopy, pinopode formation, serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and expression of progesterone receptors A and B and estrogen receptors alpha and beta. RESULT(S): Pinopode formation and regression were closely associated with increases and decreases, respectively, in serum progesterone concentration. At pinopode development, levels progesterone receptors A and B in the glandular and luminal epithelial cells decreased; this effect was mainly dependent on the absence of progesterone receptor B. Serum estrogen levels and levels of estrogen receptor alpha and beta did not correlate with pinopode formation. CONCLUSION(S): The increase in serum progesterone level and down-regulation of progesterone receptor B are important in development of pinopodes.

Adult↗
PubMed2005

Stress-induced progesterone secretion and progesterone receptor immunoreactivity in the paraventricular nucleus are modulated by pubertal development in male rats.

Male rats show a differential adrenocortical response to stress before and after pubertal development, such that prepubertal animals have a more prolonged stress-induced corticosterone response compared to adults. Whether pubertal maturation affects other adrenocortical responses to stress is currently unknown. To address this question, we assessed stress-induced progesterone secretion in both intact and gonadectomized prepubertal (28 days of age) and adult (77 days of age) male rats either before or after exposure to a 30 min session of restraint stress. We found that prepubertal males show a greater and more prolonged stress-induced progesterone response compared to adults. We also found a similar effect in castrated prepubertal and adult males, indicating the differential stress-induced progesterone response is not gonadal in origin. We also examined progesterone receptor (PR) levels by immunohistochemistry in the paraventricular nucleus (PVN) of the hypothalamus, a key regulatory nucleus of the hypothalamic-pituitary-adrenal (HPA) axis, and found lower PR protein expression in the PVN of prepubertal compared to adult males. These data indicate that in addition to corticosterone, stress-induced adrenocortical progesterone levels are differentially affected by pubertal maturation. Furthermore, these data raise the possibility of different progesterone sensitivity of the PVN before and after puberty. The significance of this differential response is presently unknown. However, given the pleiotropic effects of progesterone on male physiology and behaviour, it is likely that the disparate post-stress exposure to progesterone affects the prepubertal and adult male differently.

Animals↗
PubMed1996

Progesterone-induced immunosuppression is not mediated through the progesterone receptor.

Progesterone is a known immunosupressant in humans and may be important in treatment regimens for women with immunological and endocrinological reproductive failure. The molecular mechanism of progesterone-mediated immunosuppression remains controversial. We used the reverse transcriptase polymerase chain reaction (RT-PCR) technique to detect progesterone receptor RNA in human peripheral blood mononuclear cells (PBMCs). No expression could be documented in PBMCs from men or women representing various reproductive states. We also used the glucocorticoid receptor antagonist RU 43044 to address the hypothesis that progesterone exerts immunomodulatory effects via interactions with the glucocorticoid receptor. Both hydrocortisone (10(-6) and 10(-7) M) and progesterone (10(-5), 10(-6) and 10(-7) M) inhibited phytohaemagglutinin-induced lymphocyte proliferation in a dose-dependent fashion. RU 43044 (10(-5) M) significantly reversed the immunosuppressive effect od hydrocortisone but not that of progesterone. These studies indicate that human PBMCs do not express the classical progesterone receptor. Our results further suggest that progesterone does not mediate its immunomodulatory effects via interaction with the glucocorticoid receptor. Interaction with other members of the steroid and thyroid hormone receptor superfamily, local conversion to other steroid substances or non-classical receptor-mediated mechanisms may be involved.

Female↗
PubMed2000

Progesterone on an oestrogen background enhances prolactin-induced apoptosis in regressing corpora lutea in the cyclic rat: possible involvement of luteal endothelial cell progesterone receptors.

Preovulatory surges of both prolactin (PRL) and progesterone have been suggested to be necessary for the induction of apoptosis in the regressing corpus luteum of the cyclic rat. The aim of these experiments was to study whether the administration of PRL and/or progesterone on the morning of pro-oestrus reproduces the regressive changes that happen in the cyclic corpus luteum (CL) during the transition from pro-oestrus to oestrus, and to analyse the temporal relationships between two characteristic features of structural luteolysis (luteal cell apoptosis and accumulation of macrophages). Cyclic rats (treated at 0900 h with an LHRH antagonist to block LH secretion) were injected at 1000 h with PRL and progesterone and killed at 0, 30, 60, 90 and 180 min after treatment. The number of apoptotic cells increased progressively from 60 min after treatment onward in hormone-treated rats, whereas the number of macrophages did not change throughout the period of time considered. Rats injected with PRL plus progesterone showed significantly greater numbers of apoptotic cells than those injected with PRL alone. The luteolytic effects of progesterone were in keeping with the presence of luteal endothelial cells showing progesterone receptor (PR) immunoreactivity in pro-oestrus. Treatment of rats during dioestrus and pro-oestrus with the specific antioestrogens LY117018 and RU58668 decreased the luteolytic effects of PRL and progesterone and the number of luteal endothelial cells immunostained for PR. These results strongly suggest that the preovulatory PRL surge and the preovulatory increase in progesterone together trigger structural regression of the corpus luteum. This seems to be dependent on oestrogen-driven cyclic changes in PRs in luteal endothelial cells.

Animals↗
PubMed1980

Pituitary and gonadal function during the use of progesterone- or progesterone-estradiol-releasing vaginal rings.

Six women used polysiloxane vaginal rings impregnated with progesterone, or progesterone and estradiol. Nineteen 3-week treatment cycles were studied. Subjects kept records of bleeding. Plasma progesterone, estradiol, and gonadotropins were measured by radioimmunoassay. The patient acceptance was poor. None of the subjects experienced regular withdrawal bleedings during the treatment-free week. Fifty-three percent of the cycles were ovulatory as judged by plasma progesterone, but the plasma concentration of progesterone was low during the luteal phase. However, no pregnancies were discovered during the study period. Several high estradiol peaks were present during the treatment. Plasma LH fluctuated in the range of the normal menstrual cycle. Some suppression of plasma FSH was observed. The combination of estradiol and progesterone in the rings caused stronger suppression of FSH, but no diminution in the rate of ovulations or in disturbances of bleeding were observed in comparison to rings impregnated only with progesterone. Rings released the same amounts of progesterone in vitro and produced plasma concentrations which varied between 0.4 and 1.9 ng/ml.

Adult↗
PubMed1997

Estrogen replacement in ovariectomized rats results in physiologically significant levels of circulating progesterone, and co-administration of progesterone markedly reduces the circulating estrogen.

Estrogen and progesterone replacement in ovariectomized rats in an often-used experimental system for determination of the specific effects of these hormones. In this study, two different delivery systems and two different dosage levels of estrogen, progesterone or a combination of the two have been used. Estrogen and progesterone in the circulation have been measured in response to each treatment. It is reported that estrogen treatment (237.2 +/- 49.2 pg/mL) results in physiologically significant levels of circulating progesterone (11.1 +/- 1.3 ng/mL). Also, co-administration of progesterone (23.7 +/- 2.0 ng/mL) with estrogen decreases the level of estrogen over that seen with estrogen alone (96.7 +/- 19.2 pg/mL with progesterone vs 237.2 +/- 49.2 pg/mL without progesterone). Thus, contrary to expectations, estrogen replacement therapy is not specific to estrogen and some of the antagonistic effects of progesterone are the result of a decrease in circulating estrogen, and not a specific effect on a target tissue. Whereas the mechanism of these effects has not been determined, obvious artifactitous phenomena have been excluded as being their cause. These results could have a major impact on the interpretation of past and future experiments of this kind.

Animals↗
PubMed1994

Nasal spray administration of unmodified progesterone: evaluation of progesterone serum levels with three different radioimmunoassay techniques.

A 11.20 mg dose of progesterone was administered by nasal spray (NS) to six healthy postmenopausal women. Serial blood samples were collected and plasma progesterone was assayed by radioimmunoassay (RIA) according to three different procedures. In the first, RIA was carried out directly on plasma aliquot (Method A), in the second after diethyl ether extraction (Method B) and the third, after diethyl ether extraction and Celite column chromatography (Method C). The mean serum peak level (CMax) calculated with Method A (2.87 +/- 1.14 ng/ml) was higher than that obtained with both Method B (2.24 +/- 0.76 ng/ml) and C (1.58 +/- 0.76 ng/ml; P < 0.05); similarly the area under the curve (AUC) measured with Method A (695.79 +/- 348.24 ng h/ml) was higher than that obtained with both Method B (390.12 +/- 95.16 ng h/ml) and C (243.71 +/- 82.97 ng h/ml; P < 0.02). On the other hand, progesterone serum levels measured with Method C peaked earlier than those observed with Methods B and A (21.67 +/- 19.40, 25.83 +/- 18.55 and 35 +/- 20.70 min, respectively). These data are consistent with the high specificity of Method C for progesterone whereas the other methods could overestimate the progesterone serum levels probably measuring also progesterone metabolites particularly 5 alpha- and 5 beta-dihydroprogesterone. This study confirmed the rapid absorption of progesterone across the nasal mucosa avoiding the first-pass liver metabolism; however, a 'first-pass effect' of the nasal mucosa should be taken into consideration when progesterone is delivered by the nasal route because probably a significant portion of progestational effects are due to its active metabolites.

Administration, Intranasal↗
PubMed1976

Effect of oestradiol-17beta and progesterone on the metabolism of [1,2(-3)H] progesterone by the rabbit endometrium and myometrium.

The metabolism of [3H]progesterone in the rabbit endometrium and myometrium was studied in vitro. The major metabolities identified were 5alpha-pregnane-3,20-dione, 20alpha-hydroxypregn-4-en-3-one, 3beta-hydroxy-5alpha-preganan-20-one and 5alpha-pregnane-3beta,20alpha-diol. Other minor metabolites tentatively identified were 3alpha-hydroxy-5beta-pregnan-20-one,20alpha-hydroxy-5beta-pregnan-3-one and 5beta-pregnane-3alpha,20alpha-diol. The ability of the endometrium to metabolize progesterone on a unit weight bais was about 2.7 times that of the myometrium. The metabolism of [3H]progesterone in the rabbit uterus under the influnce of oestradiol-17beta and progesterone was studied. The ability of the oestradiol-treated rabbit uterus to metabolize progesterone was increased to 3.47 times that of the overiectomized control uterus, whereas the oestradiol-progesterone-treated rabbit uterus metabolized only 1.86 times that of the control. Study of the metabolism of progesterone with uterine subcellular preparations revealed that the 5alpha-reductase enzyme was present mainly in the nuclear fraction; 20alpha-hydroxysteroid dehydrogenase was found in the cytosol fraction and 3beta-hydroxysteroid dehydrogenase in the particulate fraction of the uterus. The metabolic pathways of progesterone in the rabbit uterine tissue are discussed.

Animals↗
PubMedDate not supplied

Administration of long-term estradiol and progesterone followed by progesterone withdrawal does not alter the plasma oxytocin secretory response to cholecystokinin or the pituitary oxytocin content in ovariectomized rats.

The hormone oxytocin (OT) is important for several pre- and postpartum events, including uterine contractions at parturition, the induction of maternal behavior, and milk ejection during nursing. During late pregnancy, OT mRNA is increased in the paraventricular nucleus (PVN) due to high estrogen and declining progesterone levels. Administration of sequential estrogen and progesterone to, followed by withdrawal of progesterone from, an ovariectomized rat also increases OT mRNA. However, pituitary OT peptide is not affected. In the present experiment, we determined if this steroid exposure alters peripheral OT secretion during a provocative stimulus to OT release, such as cholecystokinin (CCK). Adult ovariectomized Sprague-Dawley rats were implanted on day 1 with either estrogen or empty silastic capsules, on day 3 with progesterone or empty capsules, and on day 14 progesterone or empty capsules were removed. Forty-eight hrs after removal of the progesterone capsules, plasma OT was measured before and after i.v. injection of 10 micrograms/kg of CCK. At the completion of the study, pituitary glands were removed and OT peptide was measured. No significant differences were found between the sham and hormone-treated animals either in their basal or CCK-stimulated plasma OT levels or their pituitary content of OT peptide. Although sequential exposure to estradiol and progesterone followed by withdrawal of progesterone has been shown previously to increase PVN OT mRNA, neither pituitary OT immunoreactivity nor basal and CCK-stimulated release of plasma OT is affected by this treatment. Although the mechanism of this steroid effect is not yet understood, our observations suggest a unique action of gonadal steroids upon PVN OT neurons.

Animals↗
PubMed1997

Regulation of progesterone biosynthesis in the human placenta by estradiol 17 beta and progesterone.

Ex vivo addition of estradiol 17 beta to first trimester or term human placental minces caused a significant increase in the quantity of progesterone produced. Addition of an aromatase inhibitor, CGS 16949 A, or the estrogen receptor antagonist, ICI 182780, significantly inhibited progesterone production confirming the role of estradiol 17 beta in the regulation of progesterone synthesis in human placenta. RU 486 and ZK 98299, which are antagonists of progesterone receptor, significantly modulated progesterone synthesis in the human placenta but exhibited paradoxical effects on the first trimester and term placenta. We conclude that progesterone synthesis in the human placenta is regulated by estradiol 17 beta and progesterone. This is the first report providing evidence for autoregulation of progesterone synthesis in the human placenta.

Estradiol↗