Cytosolic Receptor Concentrations Research Articles

Mastоpathy is a biomarker of hormonal distress. Literature review

Mastopathy is an extensive heterogeneous group of the mammary glands pathologies, varying in its manifestations and in degree of breast cancer risk. The prevalence of mastopathy in female population is 60–80%, and this pathology has an age-related epidemiological features. On the background of gynecological diseases benign breast diseases occur in 76–97.8% of women. Frequency of mastopathy is reduced with the onset of menopause, while the risk of malignant transformation increases. Breast tissue has a high concentration of cytosolic tissue receptors to steroid compounds, so like other organs of women’s reproductive system it is susceptible to 15 hormones. Estrogen concentration in the breast connective tissue in 2–20 times higher than in blood plasma. Decisive role in the emergence of breast pathology belongs not to the absolute concentrations of hormones in blood plasma, but condition of sex steroids receptors in breast tissue. Mastodynia is a reflection of functional changes and response of breast tissue to hormonal imbalance. Proliferative mastopathy without atypia and with atypia significantly increase the risk of breast cancer. Progesterone deficiency is a key factor in the pathogenesis of dishormonal breast diseases.For timely prevention, early diagnosis of breast diseases and breast cancer, prognosis and treatment tactics, mammography, MRI and ultrasound of the gland are used, as well as various biological markers (tissue, cellular and molecular) determination, steroid hormone receptors, various growth factors and their receptors are evaluated.The timely appointment of transdermal gel Progestogel® eliminates mastodynia and other symptoms of mastopathy, and is pathogenetic treatment, which prevents the transition of functional disorders into morphological in mammary glands, reduces mammographic breast density, and thus reduces oncology risk.Thus, prevention, early diagnosis, timely pathogenetic treatment of dishormonal breast diseases reduces the risk of breast cancer.

Effect of Tamoxifen on Cytosolic Estrogen Receptor in the Different Parts of Fallopian Tube and Uterus during Ovum Transport

The effect of tamoxifen (ICI-46474) (alpha-[4-(beta-N-dimethylamino ethoxy)-phenyl]alpha'-ethyl trans stilbene on estrogen cytosolic receptor was observed in different parts of fallopian tube and uterus of rabbits during ovum transport. Tubal segments viz. ampulla (A), ampullary isthmic junction (AIJ), isthmus (I), uterine isthmic junction (UIJ) and uterus (U) were studied during the passage of ovum. Significant differences were observed in normal, drug treated and pregnant animals at 14, 24, 34, 48, 72, 144 and 168 h. In treated animals during 14 h post-coitum (p.c.) to 34 h p.c. the ampullary cytosol receptor concentration increased and suddenly decreased at 48 h p.c. whereas from 72 h p.c. to 144 h p.c. it increased gradually. Tamoxifen accelerated the rate of egg transport decreasing tubal cytosolic receptors at 48 h p.c. However, beyond 48 h p.c. receptors increased till 144 h p.c. Results suggest that tamoxifen modulated tubal cytosolic estrogen receptors during egg transport and prevents pregnancy.

Cytosolic estrogen and progesterone receptor content in the endometriotic tissues and endometrium in women with and without endometriosis

In order to have a profile of cytosolic estrogen and progesterone receptors in either endometriotic tissue or endometrium in patients with and without endometriosis a cross-sectional study was  performed  involving  43  infertile women. They consisted of 31 (72.09%) endometriosis and 12 (27.91%) non-endometriosis cases; their average age was 32 ±4 years and 32  ±3 years respectively, with the average  length  of  menstrual  cycle  31  ±8  days  and  29  ±1  days  respectively.  The endometriotic tissue was obtained by excision during ope-rative laparoscopy procedure, while the endometrium was obtained  by  biopsy following hysteroscopy  procedure.  These procedures  were  conducted  within  the  periovulatory  period  (on  Day  13-18  of  the  cycle).The  sex  steroid  receptor  content  in  the cytosol  was  measured  quantitatively  using enzyme-immunoassaymethod,  and  calculated  as  sex  steroid  receptor/cytosol  protein (fmol/ml  cytosol).  It  was  found  that  the  average cytosolic estrogen  receptor concentration  in  the  respective  tissues  were 512.99fmol/ml  in  the  endometriotic  ovary compared  with  2369.17  in  normal  ovary and  632.18  fmol/ml  in  the  endometriotic  peritoneum compared  with  9607.61  fmol/ml  in  normal  peritoneum;while 99.28  fmol/ml and 608.33fmol/ml in the endometrium of women with endometriosis and those without endometriosis respectively. The average cytosolic progesterone receptor concentration found in the respective  tissues  were 50.64fmol/ml  in  the  endometriotic  ovary compared  with  6469.42  fmol/ml  in  normal  ovary and1631.40 fmol/ml  in  endometriotic  peritoneum compared with 12466.99 in normal peritoneum, while21.26 fmol/ml and 599.61fmol/ml in the endometrium  of  women  with  endometriosis  and  those  without  endometriosis  respectively.  There  is  no  significant difference in the  receptor concentration  between  each  tissue  according  to  its  topographic  origin. However,  this  result  may  assume  that  the  responsivity  on  hormonal treatment in endometriosis cases willdepend on the cytosolic sex steroid receptor content in the sick tissues, and the peritoneal lesions will possibly give better response than those in other sites. A further clinical trial is necessary. (Med J Indones 2005; 14: 133-41)

Endogenous glucocorticoids attenuate Shiga toxin-2-induced toxicity in a mouse model of haemolytic uraemic syndrome.

The concept that during an immune challenge the release of glucocorticoids (GC) provides feedback inhibition on evolving immune responses has been drawn primarily from studies of autoimmune and/or inflammatory processes in animal models. The epidemic form of haemolytic uraemic syndrome (HUS) occurs secondary to infection with Gram-negative bacteria that produce Shiga toxin (Stx). Although Stx binding to the specific receptors present on renal tissue is the primary pathogenic mechanism, inflammatory or immune interactions are necessary for the development of the complete form of HUS. The aim of this study was to investigate the influence of endogenous GC on Stx-toxicity in a mouse model. Stx2 was injected into GC-deprived mice and survival rate, renal damage and serum urea levels were evaluated. Plasma corticosterone and cytosolic GC receptor (GR) concentration were also determined at multiple intervals post-Stx2 treatment. Higher sensitivity to Stx2 was observed in mice lacking endogenous GC, evidenced by an increase in mortality rates, circulating urea levels and renal histological damage. Moreover, Stx2 injection was associated with a transient but significant rise in corticosterone secretion. Interestingly, 24 h after Stx inoculation significant increases in total GR were detected in circulating neutrophils. These results indicate that interactions between the neuroendocrine and immune systems can modulate the level of damage significantly during a bacterial infection.

Objective measurement of breast cancer oestrogen receptor status through digital image analysis

Aims: The authors have previously described quantitative, computer-assisted analysis of oestrogen receptor status in immuno-histochemically stained sections in patients with primary breast cancer. The aim of this study was to validate the aforementioned system against the commonly used methods of assessing oestrogen receptor status.Methods: Paraffin embedded sections from 156 patients with primary breast carcinoma were stained with anti-α-oestrogen receptor monoclonal antibody (1D5) using a standard immunohistochemical protocol. Images from 10 high-powered fields were captured from each section using a digital camera mounted on a microscope and analyzed using Adobe Photoshop image analysis software. A nuclear mask was obtained by digitally selecting the nuclear area. Staining intensity in the nuclear mask was then analyzed using red-scale absorption characteristics. Manual assessment of oestrogen receptor status was performed through counting the percentages of cells that are positive from 200 randomly sampled nuclei from ten high powered fields HPF. Cut off value for positivity was taken as 10%. Cytosolic oestrogen receptor concentration was measured through enzyme immunisation. Cut off value for ER positivity was taken as 200fmol/g (wet tissue).Results: One hundred and fifty-six sections were studied of which 41 were ER negative. Median percentage positivity in the remainder was 90% (17–100) by manual assessment. The median red scale value was 108 (58–156). A close correlation was observed between median optical density of the nuclear mask and percentage positivity assessed manually (P<0.0001). There was a significant correlation between the optical density of the nuclear mask and cytosolic oestrogen receptor concentration (P<0.001).Conclusion: Oestrogen receptor positivity can be accurately assessed through digital image analysis. This process offers objective data regarding the amount of oestrogen receptors within the nuclei as well as the percentage of nuclei, which express oestrogen receptors.

Progesterone and oestrogen receptors in the female genital tract throughout pregnancy in tammar wallabies

The tammar, Macropus eugenii, is a monovular macropodid marsupial which has a post-partum oestrus and an 11 month embryonic diapause. Progesterone and oestradiol cytosol receptors were measured by Scatchard analyses and single point analysis in the lateral vagina, endometrium and myometrium of the gravid and contralateral non-gravid uterus throughout pregnancy, immediately after parturition and during seasonal reproductive quiescence. In endometrial tissues, both progesterone and oestradiol receptors doubled in concentration in both gravid and non-gravid uteri between day 0 and day 5 of pregnancy, coinciding with previously described peak values in peripheral plasma progesterone and oestrogen. Receptor concentrations in endometrial tissue during seasonal quiescence were not significantly different from those immediately after reactivation. After day 12 of pregnancy, downregulation of both progesterone and oestradiol cytosolic receptors occurred concomitant with the increase in progesterone in the peripheral plasma. However, there was a unilateral increase in oestradiol receptor concentrations in endometrium obtained from the non-gravid uterus between day 25 of the 26.5 day gestation and immediately after parturition. Myometrial receptor concentrations mirrored those of the endometrium but were lower. Concentrations of progesterone receptor in the lateral vaginae were at the lower limit of detection, while the oestradiol cytosol receptor concentrations were even lower in this tissue. Thus, the steroid receptor concentrations provide another example of local unilateral endocrine responses in the reproductive tract of the tammar. These results also indicate that the downregulation of progesterone and oestradiol receptors that occurs in both uteri in mid- and late-pregnancy is selectively and locally reversed before parturition in the non-gravid endometrium in response to the local effects of follicular oestradiol from the ipsilateral ovary.

The effects of delayed hormone replacement therapy on estrogen receptors of the cynomolgus monkey bladder and vagina.

The aim of this study was to determine cytosolic estrogen receptor content of the cynomolgus monkey bladder and vagina after hormone replacement therapy. Animals maintained without hormone therapy for 2 years after surgical menopause were randomized to receive either no hormones (OVX), conjugated equine estrogens (CEE), or estrogen/medroxyprogesterone acetate (CEE + MPA) treatment for 30 months. Estrogen receptor content of bladder and vagina cytosolic extracts was determined using a commercial enzyme-linked immunosorbent assay. Estrogen receptors were uniformly present, although the vaginal concentration was 100-fold greater than in the bladder. Estrogen and combination therapy significantly decreased cytosolic receptor content in both sites compared with controls. The cynomolgus urogenital tract remains estrogen sensitive 2 years after surgical menopause. Prolonged exposure to estrogens decreases cytosolic estrogen receptor content in a manner similar to that described for short-term estrogen therapy. These results suggest that the effects of hormone replacement on the urinary tract can be identified even if initiated years after menopause.

The effects of delayed hormone replacement therapy on estrogen receptors of the cynomolgus monkey bladder and vagina

The aim of this study was to determine cytosolic estrogen receptor content of the cynomolgus monkey bladder and vagina after hormone replacement therapy. Animals maintained without hormone therapy for 2 years after surgical menopause were randomized to receive either no hormones (OVX), conjugated equine estrogens (CEE), or estrogen/medroxyprogesterone acetate (CEE + MPA) treatment for 30 months. Estrogen receptor content of bladder and vagina cytosolic extracts was determined using a commercial enzyme-linked immunosorbent assay. Estrogen receptors were uniformly present, although the vaginal concentration was 100-fold greater than in the bladder. Estrogen and combination therapy significantly decreased cytosolic receptor content in both sites compared with controls. The cynomolgus urogenital tract remains estrogen sensitive 2 years after surgical menopause. Prolonged exposure to estrogens decreases cytosolic estrogen receptor content in a manner similar to that described for short-term estrogen therapy. These results suggest that the effects of hormone replacement on the urinary tract can be identified even if initiated years after menopause. Neurourol. Urodynam. 17:241–247, 1998. © 1998 Wiley-Liss, Inc.

CYTOSOLIC ESTROGEN RECEPTOR CONCENTRATIONS IN THE LUMBOSACRAL SPINAL CORD FLUCTUATE DURING THE ESTROUS CYCLE

Estrogen responsive neurons have been anatomically identified with autoradiographic and immunohistochemical techniques and their distribution mapped in the lumbosacral spinal cord of female rats. Such neurons contain estrogen receptors (ERs). The present study was undertaken to: 1) quantify cytosolic estrogen receptor (ER) concentrations in the lumbosacral spinal cord and 2) determine if there is a relationship between cytosolic ER concentrations and fluctuations in serum estradiol (SE2) levels during the estrous cycle. Lumbosacral spinal segments were removed from intact cycling rats during the morning of proestrus, the afternoon of proestrus, and the morning of estrus, metestrus and diestrus. Trunk blood was collected at euthanasia and SE2 levels were determined using radioimmunoassay. Cytosolic ER concentrations were measured using a dextran-charcoal coated tube method. Concentrations of cytosolic ERs were low during estrus and metestrus, increased during diestrus with maximum concentrations during the afternoon of proestrus. These changes in ER concentrations paralleled SE2 levels measured in intact cycling animals; i.e., during estrus SE2 levels were low, but began to rise during metestrus, diestrus, and during the morning of proestrus with a maximum peak increase during the afternoon of proestrus. These data indicate there are fluctuations of cytosolic ER concentrations during the estrous cycle and that these changes coincide with changing SE2 concentrations suggesting that ER content is influenced by SE2.

Relationship between size, gill corticosteroid receptors, Na +-K + ATPase activity and smolting in juvenile coho salmon ( Oncorhynchus kisutch) in autumn and spring

Coho salmon ( Oncorhynchus kisutch) normally develop an increase in saltwater tolerance during the spring as part of the parr-smolt transformation. It has been observed that coho salmon also show increased saltwater tolerance in the autumn preceding smolting. To determine whether the high salt water tolerance observed during the autumn was similar to that occurring during smolting in the spring, a group of coho reared in lake net pens in British Columbia, Canada, were sampled from June through to the following May. Changes in gill Na +-K + ATPase activity, plasma cortisol and gill cytosolic corticosteroid receptor (CR) concentration (B max) and dissociation constant (k D) were examined. Fish examined in this study showed great variation in body size. By the November after hatch, some individuals in the population were greater than 100 g and developed silver coloration characteristic of smolts. In contrast, the smallest fish in the population were approximately 10 g in November and exhibited distinct parr marks. An intermediate group also existed that were smaller than the large fish in November and March, yet were beginning to silver and exhibited less distinct parr marks. Large fish exhibited significantly increased gill Na +-K + ATPase activity in both the autumn and spring compared to the levels found in parr. Concomitant to the changes in Na +-K + ATPase activity were an increase in plasma cortisol concentration, a decrease in CR B max and an increase in k D. Increases in k D were positively correlated with Na +-K + ATPase activity. Small- and medium-sized fish only showed the changes in gill Na +-K + ATPase activity associated with smolting during the second spring. This study showed that physiological changes associated with smolting occurred in November and May in a population of coho salmon. The accelerated rate of smolt development allowed earlier transfer of fish to salt water in November.

Characterization of renal aldosterone receptors in genetically hypertensive rats

To investigate the aldosterone responsiveness of genetically hypertensive rats, we compared characteristics of renal cytosolic aldosterone receptors from the M strain of stroke-prone, spontaneously hypertensive rats (M-SHRSP) with normotensive Wistar-Kyoto rats (WKY). In M-SHRSP, blood pressure was elevated significantly at 6 wk of age, when their plasma aldosterone concentrations were similar to those in WKY. Decreases in urine volume and sodium excretion were also observed in M-SHRSP. At 10 wk of age, M-SHRSP plasma aldosterone concentrations became significantly higher than those in WKY. On the other hand, the concentration of renal cytosolic aldosterone receptors (type I, aldosterone specific) had already increased at 6 wk of age in M-SHRSP, with no difference in affinity, and levels remained increased thereafter. There were no significant differences in molecular weights or ionic charges of either "activated" or "non-activated" aldosterone-receptor complexes between M-SHRSP and WKY, indicating that the molecular properties were similar in both groups. These results suggest that the increased concentration of aldosterone receptors in the kidneys of M-SHRSP might increase their aldosterone responsiveness and contribute to the development of high blood pressure in these animals.

Effect of Estrogen Treatment on the Peroxidase Activity and Estrogen Receptors in the Female Rabbit Urogenital Tissues

The effect of one, 4 and 8 weeks of continuous estrogenization of rabbit on peroxidase (PO) activity and on both cytplasmic and nuclear estrogen receptors was studied in the uterus, vagina, urethra and urinary bladder. Whereas the peroxidase activity in the urogenital tissue of untreated controls was near zero, after one week of estrogen treatment it increased very substantially in the uterus and vagina and much less dramatically in the urethra or urinary bladder. With continuation of estrogen treatment for 4 or 8 weeks the PO decreased by 80–90% in the uterus and vagina and by only 40% in the urethra. After one week of estrogen treatment the density of both cytosolic and nuclear estrogen receptors decreased by several fold in both the uterus and vagina, whereas it decreased by 30–50% in the urethra and bladder. The concentration of both cytosolic and nuclear receptors decreased further although less dramatically with continuing estrogen treatment, up to 8 weeks, in all tissues. These data suggest that although the general pattern of responses to estrogen showing an initial increase in PO followed by a reduction with continuing estrogen treatment is the same in all urogenital tissues, the responses seem to have a prolonged time scale in the case of lower urinary tract tissues. The quantitative aspect of the response generally corresponds with the density of estrogen receptors in the urogenital tissues.

Neural androgen receptors and scent marking of male gerbils: Modulation by females

The involvement of brain cytosolic androgen receptors in the female-induced increase in scent-marking behavior of male Mongolian gerbils was studied. Scent-marking activities and serum testosterone concentrations were measured in low-marking control males and in males with increased scent-marking activities, stimulated by the presence of conspecific females in the same room. For every individual male the concentrations and affinities of androgen receptors were determined in four parts of the brain, which contained the hippocampus, septum, corpus striatum, amygdala, stria terminalis, and the hypothalamus. Compared to the basal unstimulated period, the marking activities of male gerbils significantly increased 58% during the presence of female conspecifics in their housing room. The serum testosterone concentrations did not change significantly during female presence. The association constants of the cytosolic androgen receptors were higher in female-stimulated males compared to isolated control males. In contrast, the cytosolic receptor concentration was reduced. The difference reached significance in one of the brain parts. Individual levels in scent-marking activities could not be explained by correlation with individual androgen receptor parameters. The present results suggest that increased androgen binding in the brain may be involved in the elevation of scent-marking activities in male gerbils, caused by urinary chemical signals of female conspecifics.

Sex differences in estrogen receptor binding in the rat hypothalamus: effects of subsaturating pulses of estradiol

The effects of subsaturating pulses of estradiol on cell nuclear retention of estrogen receptors in brain regions of male and female rats was determined. In the first experiment, age-matched adrenalectomized/gonadectomized (ADX/GDX) rats were killed 1 h after i.v. injection of a subsaturating dose of free estradiol (1.0 μg/kg b. wt.) and cell nuclear estrogen receptor binding was measured in microdissected brain areas by an in vitro exchange assay. As we have previously reported with saturating doses of estradiol (3.6–36.0 μg/kg b. wt.), a greater concentration of receptors was measured in the ventromedial nucleus (VMN), periventricular preoptic area (PVPOA), and medial preoptic area (mPOA) of the female than in the same regions of the male brain. Binding levels did not differ between the sexes in the bed nucleus of the stria terminalis, arcuate nucleus, or the corticomedial amygdala. In the second experiment, GDX/ADX male and female rats received either a single or double pulse of 0.5 μg estradiol/kg b. wt. administered 6 h apart. Rats were killed 1 h after the second pulse. In animals treated with a single pulse of estradiol 1 h before sacrifice, higher concentrations of estrogen binding were measured in the female VMN and PVPOA than in the male. Except in the mPOA, the concentration of estrogen receptor binding measured was not different from that measured in animals that had received an additional, earlier pulse of estradiol. In this area, receptor concentrations were lower in male rats treated with two pulses than in males treated with one pulse. Thus, receptor dynamics in the mPOA of the male may differ from that of the female and from that of other brain regions. In the third experiment, cytosol estrogen receptor concentrations measured in untreated male and female GDX/ADX rats were compared. Consistent with our data on cell nuclear binding after exposure to estradiol, cytosol receptor concentrations in the female VMN, PVPOA and mPOA were greater than those in the male. These results extend our previous findings of regional sex differences in maximal cell nuclear estrogen binding capacity by demonstrating that these differences exist in the presence of subsaturating pulses of estradiol and that they reflect differences in cytosol estrogen receptors.

Interaction of 5-azacytidine and dexamethasone in the control of hepatic tyrosine aminotransferase

The nucleoside analog 5-azacytidine is able to induce tyrosine aminotransferase several-fold in the liver of suckling rats. Bilateral adrenalectomy abolishes this inducing effect. The drug also decreases significantly the concentration of cytosolic glucocorticoid receptor accompanied by an increase of the glucocorticoid receptor concentration in the nuclei. The antiglucocorticoid RU 486 which abolishes the induction of tyrosine aminotransferase and serine dehydratase by dexamethasone very effectively is not able to inhibit either the induction of tyrosine aminotransferase or the translocation of the glucocorticoid receptor into the nuclei by 5-azacytidine.

A Characterization of Estrogen’s Influence on Anterior Pituitary Androgen Receptor: Effect of Bromocriptine Treatment

The action of gonadal steroids are mediated through the binding to specific intracellular receptors. Our recent studies have demonstrated that estrogen (E) treatment will increase the concentration of cytosolic androgen receptor (AR) in the anterior pituitary (AP) gland perhaps reflecting in increased sensitivity of this tissue circulating androgen. However, chronic E treatment also increases AP weight and cell number. Consequently, the following studies were performed to determine the relationship between increases in AP cytosolic AR and increases in AP weight following chronic E treatment. Gonadectomized male and female Fischer 344 (F344) rats were implanted with a 5-mm Silastic capsule of 17 beta-estradiol. Control animals were sham implanted. Animals were sacrificed at 1, 3, 7 and 21 days after the commencement of E treatment and AP glands were weighed and processed for cytosolic AR and nuclear estrogen receptor (ER) content. AR and ER were determined by in vitro binding assays using 3H-dihydrotestosterone and 3H-estradiol, respectively. AP weight increased significantly by 3 days of E treatment in females and by 7 days in males (p less than 0.05). However, AP weight of E-treated males was significantly less than females throughout (p less than 0.05). Significant increases in AP cytosolic AR content (fmol bound/gland) were detected within 1 day of E treatment to female rats but not until 7 days in male rats. AP cytosolic AR content peaked at 7 days of E treatment in females and 21 days in males. AP cytosolic AR concentration (expressed as per milligram cytosol protein) peaked 3 days after E at which time there were significant E effects in both males and females.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of cytosolic sexual steroid receptors in autochthonous methylnitrosourea-induced rat mammary carcinoma following application of 2-chloroethylnitrosocarbamoyl-L-alanine linked to oestradiol or dihydrotestosterone

This study concentrated on the influence of 2-chloroethylnitrosocarbamoyl-L-alanine (CNC-L-ala) linked to oestradiol (CNA-L-ala-E2) or dihydrotestosterone (CNC-L-ala-DHT) in position 17 of the respective steroid hormone on tumour growth and receptor kinetics of methylnitrosourea-induced rat mammary carcinoma. Both compounds almost completely arrested logarithmically growing mammary carcinoma of Sprague-Dawley rats: in the first week CNC-L-ala-E2 blocked the growth of these tumours by 92% compared to untreated control animals while, in animals treated with the physically equimolar mixture of CNC-L-ala and oestradiol (positive control), tumour growth was inhibited by 51% only. CNC-L-ala-DHT arrested the tumour growth in the first week by 95%, while the respective positive control (CNC-L-ala plus dihydrotestosterone) effected a growth inhibition of 71% compared to the untreated control. These results correlate well with the influence of both drugs on the cytosolic receptor content of sexual steroid hormones in the tumours. CNC-L-ala-E2 depleted the content of oestradiol receptors and kept it down for a week, while concomitantly the content of progesterone receptors increased considerably and that of androgen receptors showed a short-lived decrease. CNC-L-ala-DHT depleted androgen receptors as well as progesterone receptors. The content of androgen receptors remained low for a week, while that of progesterone receptors recovered within 8 days. The content of oestrogen receptors showed a moderate decrease.

Cytosol and nuclear estrogen receptor binding in the preoptic area and hypothalamus of female rats during pregnancy and ovariectomized, nulliparous rats after steroid priming: Correlation with maternal behavior

In a previous study, high nuclear estrogen receptor concentrations in the preoptic area (POA) were found on Day 16 of pregnancy to prime females to respond to a subsequent low dose of estradiol benzoate (EB) after hysterectomyovariectomy by exhibiting maternal behavior in 48 hr. Receptor concentrations in the POA were found to be higher than those in the hypothalamus (HYP). The present study investigated when nuclear estrogen receptors increase during pregnancy in POA and when the difference in receptor concentrations between POA and HYP occurs. An attempt was made to reproduce these pregnancy changes with a 16-day treatment of estrogen and progesterone in Ovariectomized (OVX), nulliparous rats. In Experiment 1, we measured cytosol and nuclear estrogen receptor concentrations in the POA and HYP of female rats during pregnancy. Nuclear receptor concentrations in the POA increased beginning on Day 10, increased again on Day 16, and continued at this high level for the remainder of pregnancy. Nuclear estrogen receptor concentrations in the HYP remained at a lower level throughout most of pregnancy until Day 22 when they increased significantly. In Experiment 2, we tested the maternal behavior and measured estrogen receptor concentrations in OVX, steroid-primed, nulliparous rats after hysterectomy (H) and EB treatment. While 90% of estradiol (E) + progesterone (P)-primed females displayed short-latency maternal behavior 48 hr after H and EB treatment, 46% of E + vehicle (V)-treated controls were maternal. At 0 hr (prior to H and EB treatment), there was a significantly larger nuclear receptor accumulation in the POA but significantly attenuated receptor binding in the HYP. P treatment significantly affected cytosol and nuclear estrogen receptor dynamics. Differences in nuclear estrogen receptor concentrations were shown to be based on the number of available binding sites and not to changes in receptor affinity for estradiol.

The effect of RU 486 administered during the early luteal phase on bleeding pattern, hormonal parameters and endometrium

The purpose of the present study was to investigate the effect of a single dose of RU 486 administered very early in the secretory phase on endometrial development and levels of progesterone receptors, on plasma levels of gonadotrophins and ovarian hormones and on the pattern of menstrual bleeding. Twenty-four regularly menstruating subjects participated and were studied during a control, a treatment and a follow-up cycle. In the treatment cycle, a single dose of 200 mg RU 486 was given in the evening of the second day after the urinary LH peak. Plasma was collected from cycle day 10 until menstruation in both control and treatment cycles. The lengths of the control, treatment and follow-up cycles were equal. Three of the subjects had slight vaginal bleeding in association with RU 486 intake which, however, did not disturb their normal menstrual rhythm. Plasma levels of oestradiol, progesterone and FSH were not affected in the treatment cycle, whereas LH levels increased slightly. The elimination half-life of RU 486 was 28.6 h. An endometrial biopsy was taken 12, 36 or 84 h (LH + 3, LH + 4 and LH + 6) after drug intake (eight subjects in each group) and another biopsy was taken on the corresponding day in the control cycle. The specimens were assessed by morphometric analysis and for cytosolic progesterone receptor concentrations. Endometrial biopsies taken 12 h (on LH + 3) after RU 486 intake contained significantly (P less than 0.001) lower levels of cytosolic progesterone receptors than in the control cycle, but levels at 36 and 84 h were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of RU 38,486 on progesterone and oestrogen receptor concentrations in the decidua and placenta in early pregnancy

Decidual and placental concentrations of progesterone and oestrogen receptors in 15 women having medical terminations of pregnancy with a combination of the anti-progesterone steroid RU 38,486 and prostaglandin E1 analogue have been compared with 10 matched controls undergoing surgical aspiration of pregnancy. In the patients treated with RU 38,486, the mean (SD) decidual cytosolic and total progesterone receptor concentrations of 4.3 (5.6) and 7.6 (7.1) fmol/microgram DNA respectively were significantly lower than the levels of 18.5 (14.4) and 22.3 (17.4) fmol/microgram DNA in the control patients. Progesterone receptor concentrations in the placenta were very low in both groups. No significant change in oestrogen receptor concentrations occurred in the decidua or placenta after treatment with RU 38,486. These data indicate that there may be down-regulation of decidual progesterone receptor concentrations following RU 38,486 treatment.