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PubMed1987

Characterization of the nuclear progesterone receptor in normal human endometrium after progesterone injection.

Nuclear progesterone receptors (RPN) were characterized in the 0.4 M KCl nuclear extract of the endometrium using [3H]R5020 as a ligand, in women in the proliferative phase of the cycle (n = 5), in the midcycle (n = 5), in the secretory phase (n = 4), and in premarin-treated women (n = 3), 1-3 h following progesterone injection. The receptor character of the binding was demonstrated by high specificity for progestin binding, high saturable affinity for R5020 and a sedimentation constant of about 3S in sucrose density gradient. The RPN characteristics were similar in all 4 groups and were also similar to those of the remaining cytosolic RP. Despite the fact that total RP levels differed in all 4 groups, the percentage of the receptor that was measured in the nuclear extract was similar in all groups and ranged from 52 to 61% of the total RP levels.

Adult↗
PubMed2006

Progesterone membrane receptor component 1 expression in the immature rat ovary and its role in mediating progesterone's antiapoptotic action.

Progesterone receptor membrane component-1 (PGRMC1) interacts with plasminogen activator inhibitor RNA binding protein-1 (PAIRBP1), a membrane-associated protein involved in the antiapoptotic action of progesterone (P4). In this paper, the first studies were designed to assess the ovarian expression pattern of PGRMC1 and PAIRBP1. Western blot analysis revealed that spontaneously immortalized granulosa cells (SIGCs) as well as granulosa and luteal cells express both proteins. Luteal cells were shown to express more PGRMC1 than granulosa cells. Immunohistochemical studies confirmed this and demonstrated that PGRMC1 was present in thecal/stromal cells, ovarian surface epithelial cells, and oocytes. PAIRBP1 was also expressed in thecal/stromal cells and ovarian surface epithelial cells but not oocytes. Furthermore, PAIRBP1 and PGRMC1 were detected among the biotinylated surface proteins that were isolated by avidin affinity purification, indicating that they localized to the extracellular surface of the plasma membrane. Confocal microscopy revealed that both of these proteins colocalize to the plasma membrane as well as the cytoplasm. The second studies were designed to assess PGRMC1's role in P4's antiapoptotic actions. These studies showed that overexpression of PGRMC1 increased 3H-P4 binding and P4 responsiveness. Conversely, treatment with a PGRMC1 antibody blocked P4's antiapoptotic action. Taken together, the present findings indicate that both PAIRBP1 and PGRMC1 show a similar expression pattern within the ovary and colocalize to the extracellular surface of the plasma membrane. At the plasma membrane, these two proteins interact to form a complex that is required for P4 to transduce its antiapoptotic action.

Animals↗
PubMed1993

Regulation of progesterone receptor gene expression and growth in the rat uterus: modulation of estrogen actions by progesterone and sex steroid hormone antagonists.

Although the rat uterus has often been used as a model to study estrogen action, relatively little is known of the mechanism(s) by which estrogen regulates uterine progesterone receptor (PR) levels in this species. In the present study, we used immature ovariectomized rats to examine the regulation of PR gene expression and growth in the uterus by estradiol (E2) as well as hormonal modulators of E2 action, namely progesterone (P), the antiestrogen LY117018 (LY), and the antiprogestin RU486. Northern blot analyses revealed eight PR mRNA species ranging in size from 3.3-14 kilobases, with the most abundant being 7.1 kilobases. E2 treatment caused rapid time- and dose-dependent increases in the steady state levels of PR mRNA, which peaked at 24 h (6-fold increase) and declined thereafter. All eight PR mRNA transcripts increased proportionally in response to E2. Immunoblot analyses indicated that these changes were accompanied by increases in PR protein (6-fold increase by 48 h), which continued to accumulate over time, unlike PR mRNA, which decreased despite continued E2 exposure. In contrast to the stimulatory effect of E2 on PR, the levels of immunoreactive estrogen receptor were reduced to about 15% of the control value by E2 within 48 h and remained low throughout the remaining treatment period. Treatment with P blocked the stimulatory effects of E2 on both PR mRNA and protein. These antagonistic actions of P were prevented by simultaneous administration of RU486. LY, which caused a slight (approximately 2.5-fold) increase in PR mRNA when administered alone, was an effective antagonist of E2-stimulated increases in PR mRNA. However, LY was incapable of completely antagonizing E2-stimulated increases in PR protein. The differences between the profiles of the time-dependent increases in PR mRNA and protein in response to E2, as well as the different sensitivities of these two end points to the antagonistic actions of LY, highlight the lack of direct correspondence between these two end points and suggest that E2 may be acting through distinct mechanisms (transcriptional and posttranscriptional, for example) to increase the levels of PR in the rat uterus. Our results indicate that E2 rapidly increases uterine PR expression and growth, and that P as well as sex steroid hormone antagonists are important modulators of these E2 actions in the rat uterus.

Animals↗
PubMed1995

The 5'-flanking region of the ovine follicle-stimulating hormone-beta gene contains six progesterone response elements: three proximal elements are sufficient to increase transcription in the presence of progesterone.

Progesterone (P4) can alter the synthesis and secretion of FSH from pituitary gonadotropes of sheep. In this study, the 5'-flanking region (4.7 kilobases) of the ovine FSH beta gene was tested for binding by human progesterone receptors (hPR), using an immunoprecipitation technique. Three fragments were bound by hPR. Competition experiments using homologous and heterologous DNA fragments revealed this binding to be specific and of high affinity (Kd = 1.2-47 nM). The fragment sequences were screened for potential P4 response elements (PREs). Six PRE-like elements were found among the three immunoprecipitated fragments. Band shift experiments discerned that each of these PRE-like sequences could be bound by hPR. In functional studies, each of the PRE-like elements could enhance the expression of a reporter gene driven by a heterologous promoter in a hormone-dependent manner. The 5'-flanking region of the ovine FSH beta gene was tested for P4 responsiveness using a luciferase reporter. In the presence of P4, there was a 2- to 3-fold increase in luciferase activity when the entire 4.7 kilobases of the 5'-flanking sequence were present, whereas no increase was seen in a construct that contained only 84 basepairs 5' to the transcription start site. This effect on transcription was dose dependent for P4. Deletion studies revealed that the three PRE-like elements closest to the transcription start site (-250 to -137) were sufficient to create the hormone-dependent enhancement. These results indicate that the 5'-flanking sequence of the ovine FSH beta gene contains sequences capable of being bound by hPR and may be responsible for the effects of P4 on FSH beta synthesis and secretion. This study is the first to show binding and function of PR for a gonadotropin gene.

Animals↗
PubMed1995

Progesterone receptor messenger ribonucleic acid in the primate corpus luteum during the menstrual cycle: possible regulation by progesterone.

In classical target tissues, progesterone (P) down-regulates its own receptor, yet in the primate corpus luteum, progesterone receptors (PRs) exist within a very high local P milieu. The percentage of luteal cells staining PR-positive by immunocytochemistry is highest at the midluteal phase of the menstrual cycle during the period of peak serum P. To investigate the regulation of luteal PRs, we developed a solution hybridization/ribonuclease protection assay for the analysis of PR messenger RNA (mRNA) in macaque corpora lutea (n = 3-4/group). A 332-basepair fragment of the macaque PR complementary DNA corresponding to the hormone-binding region was used as a template for riboprobe production; the specific hybridization of this riboprobe with PR mRNA was confirmed with Northern analysis. P regulation of luteal PR mRNA was investigated by administering trilostane, a 3 beta-hydroxysteroid dehydrogenase inhibitor, to female rhesus macaques beginning on day 6 or 7 of the luteal phase, which reduced serum P until the time of lutectomy. By 18 h after trilostane treatment, luteal PR mRNA levels were significantly elevated compared to untreated control values (mean +/- SEM, 2.0 +/- 0.4 vs. 0.7 +/- 0.3; P < 0.05). Reduction in P levels for 4 days after trilostane administration decreased luteal PR mRNA levels compared with control values (0.50 +/- 0.02 vs. 1.1 +/- 0.2; P < 0.05). To characterize changes in PR mRNA during the lifespan of the corpus luteum, mRNA levels in luteal tissues from the early, mid-, mid-late, and late luteal phases were determined. PR mRNA levels were lowest during the early luteal phase and increased (P < 0.05) 3-fold by the mid-late luteal phase; this higher PR mRNA level was maintained throughout the remainder of the luteal phase. These data indicate that P or a metabolite may acutely regulate primate luteal PR mRNA in a manner consistent with PR regulation in classical P target tissues. In contrast, PR mRNA levels parallel increases in P and PR-positive luteal cells during the early, mid-, and mid-late portions of the luteal phase. High PR mRNA levels are maintained during luteal regression as P and the percentage of PR-positive cells decline, suggesting that PR and PR mRNA are regulated in an asynchronous manner during the lifespan of the corpus luteum in the menstrual cycle.

3-Hydroxysteroid Dehydrogenases↗
PubMed1979

Estrogen and progesterone receptors in human breast cancer with concomitant assay of plasma 17beta-estradiol, progesterone, and prolactin levels.

The specific estrogen receptor in the cytosol of human breast cancer tissue was assayed in 217 primary cases. The specific progesterone receptor was also assayed in 48 cases as evidence of estrogen action on the tissue. Both receptors were positive in 45.8% of all cases. Plasma 17beta-estradiol and progesterone were assayed concomitantly with these steroid receptors. The higher hormone levels were found in the cases with fewer receptor binding sites. The relationship between 17beta-estradiol levels in tumor cytosol and the number of binding sites was more clearly observed. Plasma prolactin levels, however, showed no correlation with the number of receptor binding sites or the plasma levels of sex steroids. None of these assayed substances had a clear correlation with the histological type of tumor or the clinical stage of the disease.

Binding Sites↗
PubMed1986

Labor in humans: 1. Progesterone, 20 alpha-dihydro-progesterone, estrone and 17 beta-estradiol in near placental and most distant human amnion and chorion laeve in various stages of labor at term.

In some species the onset of labor is regulated by changes in the estrogen/progesterone ratio. The same change in fetal membranes has been suggested to be one of the triggering mechanisms of labor in humans. In order to examine if a gradient in steroid concentration existed in fetal membranes and if changes in concentrations could be observed with the onset and advancing labor, the concentration of progesterone (P), 20 alpha-dihydro-progesterone (20 alpha-OHP), estrone (E1) and 17 beta-estradiol (E2) were determined by specific radioimmunoassay in the near placental and most distant regions of human amnion and chorion laeve obtained at term, before, at the onset and in advanced labor. Both estrogen and progestin concentrations in the chorion were higher than in the amnion. No gradient in the concentration of steroids was found. No statistically significant differences in estrogen and progestin levels were associated with the onset of labor.

20-alpha-Dihydroprogesterone↗
PubMed1985

Plasma testosterone, estradiol, progesterone and 17-hydroxy-progesterone responses to single-dose stimulation with human chorionic gonadotropin in chronic male alcoholics.

Ten chronic male alcoholics presenting with hypogonadism but without overt liver failure were examined under basal conditions and after stimulation of the testicular steroidogenesis with a single dose of human chorionic gonadotropin (hCG, 2,000 IU im). Plasma concentrations of testosterone (T), 17 beta-estradiol (E2), progesterone (P) and 17-OH progesterone (17-OHP) were measured between 08:00-09:00 prior to injection and then every 24 h at the same time in the morning until the 96th hour following the injection. Controls were 10 male adult volunteers, examined under the same conditions. Four alcoholics underwent a second hCG stimulation after 10 day controlled abstinence from alcohol. Basal plasma T and P were significantly decreased and increased respectively in the alcoholics (p less than 0.001) whereas E2 and 17-OHP were much the same in both groups. The magnitude of the T response to hCG injection was significantly lower in the alcoholics at any considered time (p less than 0.001). The E2 response, too, was lower, whereas the ratio E2 change/T change after hCG was higher. The response peak occurred earlier for E2 than for T both in controls and alcoholics. The mean percent change at 24 h and the mean maximum increase of 17-OHP were higher in the alcoholics (p less than 0.01 and p less than 0.05 respectively). An increase in P after hCG was observed in only 5 alcoholics (responders), while some subjects displayed paradoxical decreases. Abstinence was always followed by an increased T response and a decreased 17-OHP response. The E2 response was unchanged and two P responders displayed an increased response.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1992

Effect of progesterone supplementation in repeat-breeder cattle on conception and plasma progesterone.

Reposital-type progesterone (75 mg/d for cows, 40 mg/d for heifers) or saline were administered to 24 Holstein cattle to assess the effects of exogenous progesterone (P) on fertility in repeat-breeders. Treatments were administered daily from day 6 to 10 after fourth, fifth and sixth insemination. Cumulative conception rate (57.1%) for the fourth through sixth insemination was affected by lactation number, service number, plasma P (4.67 ng/ml for pregnant cows vs 4.06 ng/ml for nonpregnant cows) and corpus luteum size on days 5 and 15. Plasma P concentrations were affected by day of cycle and size of corpus luteum on both ovaries on day 15. A treatment by day interaction accounted for higher plasma P in P-treated cattle than saline-treated cattle from day 5 through 15. Administration of exogenous P during early life of the corpus luteum in the repeat-breeder increased plasma P. Higher plasma P was associated with insemination success.

Animals↗
PubMed1989

Two progesterone receptors in the oviduct of the freshwater turtle Chrysemys picta: possible homology to mammalian and avian progesterone receptor systems.

Two progesterone receptors in the oviduct of the freshwater turtle Chrysemys picta: possible homology to mammalian and avian receptor systems. Here we report the characterization of two specific progesterone receptors in nuclear extracts of the turtle oviduct. The receptors differ in dissociation constants (2.8 nM vs 27 nM) which can be separated on DEAE-Sepharose, the former eluting at 0.08 M KCl and the latter at 0.20 M KCl. [3H]R5020 photoaffinity labeling SDS-PAGE revealed that the 2.8 nM moiety migrates with an apparent molecular weight of 80 +/- 5 kDa and the 27 nM moiety migrates with an apparent molecular weight of 120 +/- 5 kDa. These receptors are termed PR-A and PR-B due to their molecular mass and elution profiles. DNA-cellulose chromatographic studies show that both bind DNA-cellulose with the PR-A eluting at 0.09 M NaCl and PR-B eluting between 0.20-0.21 M NaCl. In reproductively inactive turtles (from the months of January and February) estradiol is undetectable, and PR-B is absent as determined by Scatchard analysis, [3H]R5020 photoaffinity labeling electrophoretic studies and DEAE-Sepharose and DNA-cellulose chromatography. In these animals PR-B can be replenished by estrogen treatment, suggesting a physiological role for both PR-A and PR-B and dependence of PR-B on estradiol.

Animals↗
PubMed1983

Influence of treatment with prostaglandin synthesis inhibitor or progesterone on cytotoxic activity and progesterone binding capacity of lymphocytes during pregnancy.

Cytotoxic activity and progesterone binding capacity of lymphocytes obtained from women with threatened preterm labour were tested before and during treatment with acetylsalicylic acid or 17-hydroxyprogesterone caproate. Cytotoxic activity of the lymphocytes significantly decreased (p less than 0.001), while progesterone binding capacity significantly increased (p less than 0.001) following the introduction of the treatments. No changes in these parameters were observed on lymphocytes of untreated women. Preterm delivery occurred more frequently among untreated women than among women treated with acetylsalicylic acid (p less than 0.01) or those treated with 17-hydroxyprogesterone caproate (p less than 0.05).

17-alpha-Hydroxyprogesterone↗
PubMed1995

Lack of estrogenic potential of progesterone- or 19-nor-progesterone-derived progestins as opposed to testosterone or 19-nor-testosterone derivatives on endometrial Ishikawa cells.

Estrogen receptors of human endometrial cancer Ishikawa cells were found to be present in moderate amounts (160-200 fmol/mg protein), and to specifically bind moxestrol (R2858) with a very high affinity characterized by a Kd around 60 pM, when measured under equilibrium conditions. The binding specificity respected a decreasing order as follows: estradiol (E2: 100%) > 4-hydroxy-tamoxifen (4OHTAM: 52.7%) > estriol (E3: 5.7%) > estrone (E1: 2.1%) > TAM (0.2%). The induction of alkaline phosphatase activity (APase) used as an estrogen-specific response, confirmed the intrinsic estrogenicity of progestins derived from 19-nor-testosterone (19NT): norethindrone (NOR), norethynodrel and levonorgestrel, at concentrations ranging from 10(-8) to 10(-6) M. The effect of NOR was partially blocked by the antiestrogen 4OHTAM, which was also partially agonistic in this model, but neither by the antiprogestin mifepristone (RU486) nor by the aromatase inhibitor aminoglutethimide. A simulatory effect was also detected at 10(-7) or 10(-6) M with ethindrone, the testosterone- (T) derived progestin homologous to NOR, and with both androgenic parent-compounds, i.e. T and 19NT themselves. In contrast, progesterone (P) derivatives like medroxyprogesterone acetate (MPA) and chlormadinone acetate (CMA) remained totally inactive, as well as 19-nor-progesterone (19NP) itself or its progestagenic derivatives: ORG 2058 and nomegestrol acetate (NOM). Structure-activity relationships deduced from these studies suggest that it is not the absence of the 19-methyl group which can account for the estrogenic potential of the so-called "19-norprogestins", but rather their steroid structure derived from T in a broad sense (including the 19NT derivatives), as opposed to the non-estrogenic therapeutic progestins derived from P like MPA or CMA, or from 19NP like NOM.

Adenocarcinoma↗
PubMed2004

Effect of exogenous progesterone and oestradiol on plasma progesterone concentrations and follicle wave dynamics in anovulatory anoestrous post-partum dairy cattle.

The effect of exogenous progesterone (P4) and of oestradiol benzoate (ODB) on plasma progesterone concentration and follicle dynamics was studied in anovulatory anoestrus (AA) post-partum pasture-fed dairy cattle. Cows (n=32) were defined AA based on not detecting a corpus luteum upon transrectal ultrasonography of the ovaries. Cows were randomly assigned to treatment with an intravaginal P4-releasing device containing 1.56 g of P4 (1Q; Cuemate, Pfizer Animal Health, Auckland, NZ; n=11) or with modified devices with double (2Q; n=11) or triple (3Q; n=10) the normal P4 dose for 8 days. Half of each group received 2 mg ODB at device insertion (Day 0) while the other half did not receive ODB at this time. All cows were treated with 1 mg ODB 1 day after intravaginal device removal (Day 9). Ultrasonography occurred daily until either ovulation or Day 15 whichever occurred sooner. Blood samples were drawn on Days 0, 1, 3, 5, 7, 8, 9, 15 and 22 for plasma P4 determination. Increasing P4 dose was associated with an increase in plasma P4 concentration during the time of device insertion (P <0.05). The highest P4 dose was associated with a delay in emergence of, but a shorter interval from emergence to maximum diameter and ovulation of, the subsequent dominant follicle (DF2) compared to the lowest P4 dose. Treatment with ODB resulted in a delay in emergence of DF2 (4.2 (0.4) versus 2.0 (0.4) days (S.E.M.) to emergence for ODB versus no-ODB; P=0.01), a smaller maximum diameter of DF2 (15.2 (0.5) versus 17.9 (0.6)mm (S.E.M.) for ODB versus no-ODB; P <0.01), a shorter interval to maximum DF2 diameter (5.0 (0.3) versus 6.8 (0.3) days (S.E.M.) for ODB versus no-ODB; P=0.03), a shorter interval from DF2 emergence to ovulation (6.3 (0.4) versus 8.5 (0.4) days (S.E.M.) for ODB versus no-ODB; P=0.02) and a tendency for a lower average plasma P4 concentration post-ovulation (i.e. average of Days 15 and 22; 2.5 (0.4) versus 3.4 (0.4) ng/ml plasma P4 for ODB versus no-ODB, respectively; P=0.08). The DF present at device insertion, was still present at device removal in three (9%) cows of which two were treated with 1Q + no-ODB and one with 3Q + ODB. It is concluded that increasing P4 dose and ODB treatment are associated with a delay in subsequent follicle wave emergence and more rapid follicle growth. Oestradiol benzoate treatment also tends to reduce the plasma P4 concentration in the subsequent luteal phase in post-partum, anoestrous dairy cattle.

Animals↗
PubMed2005

Immunofluorescent localization of a novel progesterone receptor(s) in a T47D-Y breast cancer cell line lacking genomic progesterone receptor expression.

OBJECTIVE: To identify a novel nongenomic progesterone receptor (PR), PR-M, in T47D-Y breast cancer cells lacking genomic PR expression. METHODS: Immunofluorescent staining of T47D and T47D-Y breast cancer cells with selective anti-PR antibodies and ligand binding. Transient transfection of breast cancer cells with a cDNA expressing PR-M with a carboxy terminal green fluorescent protein. RESULTS: In the T47D-Y cell line, lacking expression of genomic PR, plasma membrane-bound and intracellular PR(s) are identified with anti-PR antibodies directed to the hormone-binding domain but not with an antibody directed to the amino terminus. A plasma membrane PR is also evident by immunofluorescent ligand binding. Expression of a novel truncated PR (PR-M) tagged with green fluorescent protein showed intracellular localization. CONCLUSIONS: These studies support the expression of a novel, truncated PR (PR-M) in a breast cancer cell line known to lack expression of genomic PR. This observation raises the possibility of progesterone action in breast cancer cells classically considered nonresponsive due to lack of genomic PR expression.

Animals↗
PubMed2003

Effect of treatment with progesterone and oestradiol when starting treatment with an intravaginal progesterone releasing insert on ovarian follicular development and hormonal concentrations in Holstein cows.

Ovarian follicular development and concentrations of gonadotrophin and steroid hormones were studied in non-lactating Holstein cows following administration of progesterone (P(4)) or oestradiol benzoate (ODB) at the start of treatment with an intravaginal progesterone releasing insert (IVP(4)) in a 2 by 2 factorial experiment. Cows were treated at random stages of the oestrous cycle with an IVP(4) device (Day 0) and either no other treatment (n=8), 200 mg of P(4) IM (n=9), 2.0 mg of ODB IM (n=8) or both P(4) and ODB (n=9). Seven days later devices were removed and PGF(2alpha) was administered. Twenty-four hours later 1.0mg of ODB was administered IM. Oestrus was detected in 97.1% and ovulation in 64.7% (effect of treatment, P=0.41) of cows within 96 h of removing inserts. In the cows that ovulated, day of emergence of the ovulatory follicle was delayed (P<0.01) and more precise (P<0.05) in cows treated with ODB compared to the cows treated with P(4). Interval from wave emergence to ovulation and the diameter of the ovulatory follicle was less (P<0.05) in cows treated with ODB compared to cows treated with P(4). Combined treatment with P(4) and ODB at the time of starting treatment with an IVP(4) device did not significantly change the pattern of ovarian follicular development compared to treatment with ODB alone. Concentrations of LH and FSH in plasma were less in cows treated with ODB between Days 0 and 4 (P<0.05) while treatment with P(4) increased concentrations of FSH in plasma between Days 0 and 4 (P<0.05). When anovulatory cows were compared to ovulatory cows, diameters of follicles (P<0.001) and growth rate of follicles (P<0.01) were less in anovulatory cows between Days 7 and 9, while concentrations of FSH in plasma were greater (P<0.01), concentrations of LH similar (P>0.90) and concentrations of oestradiol were less (P=0.01) in the anovulatory cows between Days 4 and 10. Our findings support a hypothesis that ovarian follicular development following administration of P(4) or ODB at the start of treatment with an IVP(4) device differs. Anovulatory oestrus may have been associated with reduced maturity and/or later emergence of ovarian follicles.

Administration, Intravaginal↗
PubMed1997

Effect of 48 h treatment with 17 beta-oestradiol or progesterone on follicular wave emergence and synchrony of ovulation in Bos indicus cows when administered at the end of a period of progesterone treatment.

The objective of this study was to determine the effect of treatment with additional progesterone (P4) or 17 beta-oestradiol (E2) at the end of a period of P4 treatment on ovarian follicular development, ovulation time, and plasma gonadotrophin and steroid hormone concentrations of Bos indicus cows. Initially, two injections of PGF2 alpha were given 14 days apart, and at the time of the second injection (Day 0) all cows received a single P4-releasing controlled internal drug release (CIDR) device that was removed 10 days later. Control cows (Group 1, n = 8) received no other treatment. On Day 8, cows in Group 2 (n = 8) and Group 3 (n = 8) received either a s.c. implant containing E2, or a second CIDR device, respectively. All CIDR devices and E2 implants were removed at a similar time on Day 10. Treatment with E2 or P4 delayed mean (+/- SD) time of ovulation (113.1 +/- 25.6 h, 153.4 +/- 44.5 h and 150.8 +/- 25.1 h for Groups 1, 2 and 3, respectively; P < 0.05) and the mean time (+/- SD) of the luteinising hormone (LH) peak (87.4 +/- 24.5 h, 124.3 +/- 45.0 h and 122.3 +/- 25.04 h for Groups 1, 2 and 3, respectively; P < 0.05). Both treatments delayed the mean (+/- SD) day of emergence of the ovulatory follicle (7.7 +/- 3.6 days, 11.3 +/- 1.7 days and 11.1 +/- 1.5 days for Groups 1, 2 and 3, respectively; P < 0.05), and reduced the variability in the day of emergence of the ovulatory follicle (P < 0.05) compared with the control cows. Variability in age and duration of dominance of the ovulatory follicle was greater in control animals compared with treated animals (P < 0.05). Treatment with E2 on Days 9 and 10 did not alter mean concentrations of gonadotrophins in the cows in Group 2 compared with control cows (P > 0.05), whereas treatment of cows with an additional CIDR device resulted in greater mean concentrations of FSH and lesser concentrations of LH on Day 9 (P < 0.05) compared with cows in Groups 1 and 2. By Day 10 mean concentrations of gonadotrophins were similar among cows in all three groups. Concentrations of E2 were less in cows in Group 3 compared with cows in Groups 1 and 2 from Day 9 to Day 11 (P < 0.05). We conclude that treatment with either E2 or P4 can influence the pattern of ovarian follicular development and ovulation in cattle; however, the mechanism of action of the two treatments may differ. Atretogenic treatments for ovarian follicles applied at the end of a period of progesterone treatment did not improve synchrony of ovulation.

Animals↗
PubMed1997

Reversal of progesterone-induced sequential inhibition by progesterone metabolites.

Previous reports have shown that intrabrain administration of progesterone (P) ring A-reduced metabolites into the medial preoptic area (MPOA) and ventromedial hypothalamus (VMH) induces facilitation of female sexual behavior in ovariectomized (ovx) rats pretreated with estrogen. Present studies were designed to explore the possibility that ring-A reduced progesterone metabolites might play a role in controlling the duration of estrous behavior. To this aim ovariectomized (ovx) Sprague Dawley rats implanted with guide cannulae directed towards the VMH or the MPOA were submitted to a systemic hormonal treatment to provoke P-induced sequential inhibition (estradiol benzoate (EB) at time O + P at 44 h + P at 68 h). The second dose of P was administered simultaneously with the i.c. implantation of one of the following P metabolites: 3 beta-hydroxy-5 beta-pregnan-20-one (5 beta,3 alpha P), 3 alpha-hydroxy-5 beta-pregnan-20-one (5 beta,3 alpha P) or 3 beta-hydroxy-5 beta- pregnan-20-one (5 alpha,3 beta P) into the MPOA or VMH. Lordosis behavior was evaluated by the lordosis quotient (LQ = number of lordosis/10 male mount x 100) and by the percentage of responding subjects. Results show that 5 beta,3 beta P implanted into the VMH or MPOA counteracted the sequential inhibitory effect induced by systemic administration of P.5 alpha,3 beta P was also able to counteract sequential inhibition, but with less potency and only in the VMFI. Results showed that P-induced sequential inhibition can be counteracted by intrabrain administration of ring-A reduced progestins in both the VMH and MPOA. Data are discussed in terms of a putative physiological role of naturally occurring P metabolites in P-mediated female sexual behavior expression.

Animals↗
PubMed1995

Nonsteroidal progesterone receptor ligands. 2. High-affinity ligands with selectivity for bone cell progesterone receptors.

A novel series of nonsteroidal heterocycles was discovered which display cell-type selective, high-affinity (nanomolar) binding to the progesterone receptors from TE85 osteosarcoma cells but > 1 microM binding affinity to the progesterone receptors from T47D and ZR75 human breast carcinoma cells. Structure-activity relationships were developed for a set of these compounds, and a representative analog 1-(3,4-dichlorobenzoyl)-3-phenyl-1,4,5,6-tetrahydropyridazine++ + (1i, RWJ 25333) was chosen for further evaluation. RWJ 25333 stimulated the in vitro proliferation of human osteoblast-like cells but not human breast cells.

Bone Neoplasms↗