Number Of Progesterone Receptors Research Articles

Changes in Uterine Estrogen and Progesterone Receptors during Delayed Implantation And Early Implantation in the Spotted Skunk

Although the exact cause(s) of embryonic diapause in the western spotted skunk and other carnivores remains unknown, it has been hypothesized that it may be due to levels of ovarian hormone secretion that are insufficient to promote a uterine environment conducive to continuous embryonic development and implantation. Immunocytochemistry was used to determine whether changes in abundance or distribution of estrogen receptors (ER) and progesterone receptors (PR) may be associated with the cessation or renewal of embryonic development. Thirty pregnant skunks were killed during delayed implantation and periimplantation periods. ER and PR were detected in luminal and glandular epithelium, endometrial stroma, vasculature, and myometrium of the uterus during the period of delayed implantation. There was a significant reduction of both ER and PR receptors during the periimplantation period. The most pronounced change was the complete loss or reduction in staining intensity for PR and ER in the luminal epithelium during the first 2-3 days after implantation. These findings suggest that the failure of skunk blastocysts to undergo continuous development and implant without a prolonged period of diapause is not the result of an insufficient number of ER or PR in the uterus. The data also indicate that renewed embryonic development and implantation is not associated with an increase in these uterine steroid receptors.

Effects of intrahypothalamic administration of antisense DNA for progesterone receptor mRNA on reproductive behavior and progesterone receptor immunoreactivity in female rat

Since reproductive behaviors of female rats can be correlated with estrogen-induced increases in progestin binding by hypothalamic neurons, we hypothesized that specific progesterone receptor (PR) antisense DNA sequences might decrease these behaviors. Antisense oligonucleotides (15 bases), spanning the translation start site of rabbit PR mRNA, were microinjected directly among ventromedial hypothalamic neurons, and their behavioral effects were compared to control oligonucleotides composed of the same nucleotide bases in scrambled order. When applied 12 but not 24 hr after estradiol, the PR antisense treatment significantly reduced iordosis behavior, measured either as a reflex or in a mating behavior test. Notably, proceptive behaviors, which are strongly progesterone dependent, were greatly reduced in their occurrence (80% decrease). To see if PR protein was also reduced, antisense DNA was administered near the ventromedial hypothalamus on one side of the brain, while the other side received the scrambled control sequence or vehicle. The total number of PR-immunoreactive cells on the antisense side was significantly lower in the ventromedial nucleus, but not in control measurements from the medial preoptic area. Interrupting gene expression for PR, a transcription factor, in hypothalamic neurons, can have behavioral and immunocytochemical effects.

Endocrinology: Immunohistochemical sex steroid receptor distribution in endometrium from long-term subdermal levonorgestrel users and during the normal menstrual cycle

The bleeding problems experienced by users of subdermal levonorgestrel implants (Norplant) remain unexplained. The aim of the present study was to investigate the oestrogen (ER) and progesterone receptor (PR) distribution in levonorgestrel-treated endometrial biopsies from 31 subjects recruited in Jakarta, Indonesia, and to compare the sex steroid receptor immunostaining with that of endometrium from 58 normally cycling women from Melbourne, Australia. Sex steroid receptor immunoreactivity was additionally compared with days of exposure to subdermal levonorgestrel, serum oestradiol and progesterone levels and days of bleeding during a 90-day reference period. An immunohistochemical technique with an alkaline phosphatase anti-alkaline phosphatase (APAAP) detection system for use in formalin-fixed paraffin wax embedded endometrial tissue was employed. Significantly greater mean immunostaining scores of stromal PR were observed in Norplant compared with control endometrium at all stages across the cycle. No significant correlations were demonstrated between sex steroid receptor immunostaining and days of exposure to subdermal levonorgestrel, serum oestradiol or progesterone concentrations or days of bleeding during a 90-day reference period. Whether the elevated stromal PR immunostaining in Norplant-treated endometrium is a consequence of increased synthesis or reduced turnover of receptor remains unclear. As yet it is undetermined whether increased PR immunoreactivity corresponds to an increase in number of functional PR.

Phenotypic characterization of normal human placental mononuclear cells

The placenta is a rich source of immunocompetent cells. We have studied the phenotype, number and origin of placental mononuclear blood cells isolated from 32 normal term placentae using 4 color flow cytometry. Respective maternal and cord blood leucocyte preparations were also compared. Placental tissue without extraembryonic membranes was cut into small pieces and divided. One portion was washed extensively with ice-cold PBS. Both tissue portions were disrupted in a blender and cells were dissociated by using a 180μ sieve. Leucocytes were isolated by Ficoll-Hypaque density gradient centrifugation. Maternal and cord bloods were HLA typed and in cases of HLA-A2 or B7/40 disparity, monoclonal anti-HLA antibodies to these antigens showed that unwashed placental tissue contained 35% maternal and 65% fetal cells. This ratio, however, was not reflected for a given cell phenotype. In comparison, washed placental tissue contained cells of fetal origin only. Both unwashed and washed placental tissue contained fewer CD3 and CD4, but more CD8 cells than maternal and cord blood. Markers of NK cells such as, CD16, CD56, and CD57 showed this cellular phenotype to be 15 times more abundant in the placental preparations than in cord and maternal blood. The quantitative differences between peripheral blood and placental CD8 and NK cells were further explored with an antiprogesterone receptor antibody in combination with anti-CD8, anti-CD57 and anti-HLA-DR. The number of progesterone receptor (PGR) positive cells was three times higher in placental tissues than in cord or maternal blood. These data indicate that the phenotypic frequencies of certain placental leucocytes are significantly different from maternal and fetal peripheral blood. Progesterone and the presence of PGR may be important in the differential retention of placental leucocytes.

Changes in progesterone and oestrogen receptor mRNA and protein during maternal recognition of pregnancy and luteolysis in ewes.

This study characterized changes in levels of mRNA and protein for endometrial oestrogen receptors (ERs) and progesterone receptors (PRs) during luteolysis and maternal recognition of pregnancy. For cyclic and pregnant ewes, endometrium was collected on days 10, 12, 14, or 16 post-oestrus (4 ewes/day for each status) for the measurement of ER and PR mRNA and protein. The amount of receptor mRNA is expressed in relative units above background, measured from radiographs of dot-blot hybridization of total endometrial RNA with ER and PR cDNAs. At hysterectomy, jugular vein blood samples were collected and assayed for progesterone, total corpus luteum weight was recorded and, in vitro, endometrial oxytocin-stimulated inositol phosphate formation was estimated. In pregnant ewes, plasma progesterone increased gradually between days 10 and 16 (P < 0.01), corpus luteum weight was stable at approximately 0.8 g and oxytocin did not stimulate endometrial formation of inositol phosphates in vitro. In contrast, in cyclic ewes, plasma progesterone decreased from day 10 to day 16 (P < 0.01), corpus luteum weight decreased after day 14 to approximately 0.48 g (P = 0.05) and oxytocin stimulated an increase of approximately 1300% in the endometrial formation of inositol phosphates on day 16. cDNAs specifically hybridized with 1.6 and 3.1 kb transcripts for PR mRNA and a 6.5 kb transcript for ER mRNA. In cyclic ewes, the amount of PR mRNA increased from day 10 to maximum levels on days 14-16. The number of PRs decreased from day 10 (2.25 pmol/mg DNA) to day 12 (0.98 pmol/mg DNA) and then increased from day 14 to day 16 (2.8 pmol/mg DNA). In pregnant ewes, PR mRNA levels were greatest on days 10-12 and decreased by approximately 50% by day 16. In contrast, the number of PRs was relatively unchanged from day 10 to day 16 (1.53 to 1.03 pmol/mg DNA). In cyclic ewes, the amount of ER mRNA was lowest at day 10 and increased fivefold by day 16. The number of ERs remained relatively unchanged from day 10 to day 14 (6.07 pmol/mg DNA) and increased by day 16 (16.12 pmol/mg DNA). In pregnant ewes, ER mRNA decreased by approximately 80% from day 12 to day 16. Similarly, the number of ERs decreased from day 10 to day 16 (5.41 to 2.05 pmol/mg DNA). Correlations between ER mRNA and PR mRNA (r = 0.68), ERs and PRs (r = 0.50) and ER mRNA and ERs (r = 0.50) were high (P < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Progesterone, oestradiol, somatostatin and epidermal growth factor receptors on human meningiomas and their CT characteristics

The presence of progesterone, oestrogen, somatostatin and epidermal growth factor receptors of 24 meningiomas was related with their radiological CT appearance. Progesterone receptors were present in 16 of 21 (76%), oestrogen receptors in 4 of 21 (19%), somatostatin receptors on 23 of 24 (96%) and epidermal growth factor receptors on 17 of 19 (89%) meningiomas. There was no relationship between the presence of these receptors and the age or sex of the patients, tumour histology, tumour localisation, the presence of perifocal oedema, displacement of the midline cerebri or obstructive hydrocephalus on CT scan. There was a negative correlation ( P < 0.05) between the number of progesterone receptors and “malignant’ behaviour of the meningiomas on CT (e.g. the presence of necrosis, cyst formation, intratumoral haemorrhage, irregular surface and/or inhomogeneous attenuation of contrast). The observation that aggressive tumour behaviour on CT is accompanied by low numbers or absence of progesterone receptors makes these meningiomas less attractive candidates for medical therapy with antiprogestins.

Oral contraceptive (OCP) use increases proliferation and decreases oestrogen receptor content of epithelial cells in the normal human breast

The effect of ingestion of oral contraceptives (OCP) on cell proliferation and oestrogen (ER) and progesterone receptor (PR) expression of the epithelial cells of the normal human breast was compared with findings in controls not taking OCPs. Histologically normal breast tissue was removed during operation for fibroadenoma or reduction mammoplasty in 216 women whose mean age was 28.1 +/- 8.5 years (+/- SD range 14-53 years). During natural cycles the mean proportion of cells expressing ER was 3.94 +/- 3.71 (% mean +/- SD, range 0-20.8, n = 51), while of those expressing PR it was 12.1 +/- 7.1% (range 3.0-36.1, n = 47). There was a significant decline in ER during the menstrual cycle [p = 0.001 by multiple linear regression (MLR)], but there was no significant change in the proportion which expressed PR. The mean proportion of proliferating cells (LI) was 2.50 +/- 2.42 (range 0-11.5, n = 147). There was a significant increase of LI during the cycle (p = less than 0.001, MLR) and a significant inverse relationship between LI and ER (r = -0.29, p less than 0.01). Use of the OCP significantly reduced the number of cells which expressed ER and increased the LI earlier in the cycle. No effect of OCP use on the number of PR+ cells was detectable. We conclude that significant changes in the proportions of ER+ and proliferating cells occur during natural menstrual cycles. These changes are perturbed by ingestion of OCPs, so that there is greater suppression of ER and a longer period of high proliferation during the menstrual cycle. These results may explain the relationship between OCP use and the possible risk of breast cancer.

Role of Progesterone Receptors In Breast Cancer

It has been demonstrated that progesterone receptors (PRs) are at least as valuable as estrogen receptors (ERs) for predicting outcome in breast cancer patients. Retrospective analysis indicates that the presence of PRs may be the second most critical factor, after the number of positive nodes, in predicting disease-free survival, with a correlation between length of survival and number of tumor PRs. The presence of PRs has been shown to be of value for predicting response in both early and advanced breast cancer patients. In studies of assay consistency, major discordance rates were minimal in simultaneous assays, but extremely high in sequential assays of tumors that were PR-positive in initial assay. The responsible factor was interim endocrine therapy, and it was subsequently determined that the prognosis was worse for those patients whose tumors lost PR between assays.

The determination of progesterone receptors in breast cancer and their relationship to estrogen receptors

A simple method for the assay of specific progesterone receptors in breast cancer tissue is described. Progesterone receptors were detected in 63 of 74 breast cancer specimens (85%). Estrogen receptor positive tumors had a wide range of progesterone receptor concentrations, but in 77% of cases the level was above 3 fmol/mg protein. The progesterone receptor level was generally low in tumors lacking estrogen receptors, 75% of the samples having concentrations between 0 and 3 fmol/mg protein. Unlike estrogen receptors, age had no influence on the number of progesterone receptors in breast cancer tissue.