scholarly journals Apoptosis, Proliferation, and Sex Hormone Receptors in Superficial Parts of Human Endometrium at the End of the Secretory Phase1

1999 ◽  
Vol 84 (5) ◽  
pp. 1737-1743 ◽  
Author(s):  
M. Dahmoun ◽  
K. Boman ◽  
S. Cajander ◽  
P. Westin ◽  
T. Bäckström

Apoptosis with one regulator, Bcl-2, and proliferation with the marker Ki-67 were studied in 75 endometrial biopsies representing superficial parts of endometrium from 35 regularly menstruating women premenstrually and menstrually. Hormonal withdrawal was studied in serum samples and potentiated in epithelium by the decreasing 17β-estradiol and progesterone receptor scores 4 days premenstrually. The apoptotic index increased 2 days before the onset of menstruation and peaked on the second menstrual day. The high apoptotic index together with low proliferation in endometrial epithelium at the end of the menstrual cycle are similar to the involution process seen in other hormone-dependent organs. In stroma, the apo-ptotic index increased later, at the onset of menstruation, and the increase was lower than that in epithelium. The Ki-67 index increased during the last 3 days of the secretory phase, parallel with an increasing progesterone receptor score and decreasing Bcl-2 staining, and peaked at the onset of menstruation. The findings in stroma concur with high proliferation at the end of the menstrual cycle and high cell turnover during menstruation, suggesting the participation of stroma in the renewal process of endometrium.

2000 ◽  
Vol 12 (2) ◽  
pp. 59 ◽  
Author(s):  
Noriyuki Takai ◽  
Tami Miyazaki ◽  
Isao Miyakawa ◽  
Ryoji Hamanaka

The enzyme, polo-like kinase (PLK), is a mammalian serine/threonine kinase involved in cell cycle regulation. A great deal of evidence regarding the role of PLK in the cell cycle has been obtained through studies of cultured cells, though little is known about its function or even expression in vivo. The endometrium undergoes rapid proliferation and differentiation under ovarian steroid hormone control during the 28-day cycle. Thus, normal endometrium provides an excellent model in which to study the hormone dependency of PLK expression. In the present study, we examined the features of PLK expression in 20 samples of normal human endometrium during the menstrual cycle. The expression of Ki-67 and proliferating cell nuclear antigen (PCNA) were also examined as markers of proliferation. Immunohistochemical studies showed that PLK staining was detected in the basement membrane of many endometrial glands, stromal cells, and some endothelial cells. The number of PLK-positive endometrial gland cells was significantly higher in the late proliferative phase (19.16% 4.98%) and the early secretory phase (19.28% 4.99%) than in the early proliferative phase (2.60% 2.33%) or the late secretory phase (5.76% 2.16%) (P<0.0001). PLK expression seemed to be correlated with the expression of Ki-67 and PCNA in many endometrial glands and stromal cells particularly in the late proliferative phase, reflecting a role of PLK in cellular proliferation. Nevertheless, in the early secretory phase, at which point the expression of Ki-67 and PCNA decreased in endometrial glands, PLK was strongly expressed. This finding suggests that PLK may have some post-mitotic functions in certain specialized cell types. Although the highest expression of PLK was observed in the late proliferative and the early secretory phases, the expression drastically decreased in the late secretory phase. These findings, taken together, indicate that the expression of PLK in normal endometrium fluctuates over the course of the menstrual cycle, suggesting in turn that PLK is associated with hormone-dependent cellular proliferation and that hormone functions may be involved in its regulation.


2018 ◽  
Vol 20 (2) ◽  
pp. 63-67
Author(s):  
S S Aganezov ◽  
V N Ellinidi ◽  
K Yu Ponomarenko ◽  
A V Morotskaya ◽  
N V Aganezova

A comparative analysis of the levels of estradiol and progesterone in the blood, immunohistochemical parameters of estrogen receptors and progesterone in endometrium in women with a history of reproductive disorders is presented. It was found that all women had an ovulatory ovarian cycle, levels of estradiol and progesterone in the blood were within the reference values. In women with reproductive failures in the history (n=107), four types of hormone-receptor response in the endometrium were identified. In 46 (43%) women, the first (normoreceptor) type of endometrial response was detected, without significant differences from the control group (n=15) corresponding to the middle stage of the secretion phase. Hyperreceptor (hyper-estrogen-progesterone-receptor, hyper-estrogen-receptor, hyper-progesterone-receptor) types have been identified in 61 patients (57%) with reproductive dysfunctions. The endometrium corresponded to the mid secretory phase was detected in 47 (44%), inadequate secretory phase of the endometrium - in 60 (56%) women with reproductive failures in the anamnesis. All women in the control group had a full secretory change in the endometrium. In general, more than half (61 (57%)) of women with reproductive failures in the history with the ovulatory menstrual cycle with normal values of the level of progesterone in the blood showed signs of a decreased endometrial receptivity status. This indicates that the ovulatory level of progesterone in the blood is not an unconditional predictor of full secretory transformations of the endometrium.


2007 ◽  
Vol 122 (2) ◽  
pp. 125-127 ◽  
Author(s):  
S Cafer ◽  
I Bayramoglu ◽  
N Uzum ◽  
M Yilmaz ◽  
L Memis ◽  
...  

AbstractObjective:The objective was to assess the presence of Ki-67, and oestrogen and progesterone hormone receptors as well as their clinical correlates in acoustic neuroma.Methods:Medical records of 59 patients who were operated on for acoustic neuroma between 1995 and 2003 were evaluated retrospectively. Formaldehyde-fixed paraffin-embedded archival acoustic neuroma specimens of the patients were used for immunohistochemical assessments of oestrogen and progesterone hormone receptors, and Ki-67 proliferative marker.Results:Tumour sizes were small (<19 mm), medium (20–39 mm) and large (>40 mm) in 21, 35 and 3 patients, respectively. On immunohistochemistry, all samples were (+) for progesterone receptor and (–) for oestrogen receptor staining. Ki-67 staining was encountered in 34 of 59 (57.6 per cent) patients, and Ki-67 values ranged from 0 per cent to 10.9 per cent (mean 1.36 per cent). There was no correlation between Ki-67, gender, tumour size and symptoms of the patients (p > 0.05).Conclusion:Oestrogen is not an important hormone in acoustic neuroma due to the absence of oestrogen receptor expression in the tissue samples. Since the progesterone receptor is expressed in all acoustic neuroma samples, further studies are necessary to find out about the inhibitory effect of antiprogesterone treatment on acoustic neuroma growth, which may be important particularly in elderly people or high-risk patients. Although Ki-67 is expressed in the majority of acoustic neuromas, it is not an important marker in clinical practice due to a lack of any correlation with the clinical parameters.


2017 ◽  
Vol 77 (07) ◽  
pp. 756-764 ◽  
Author(s):  
Joachim Alfer ◽  
Lars Happel ◽  
Ralf Dittrich ◽  
Matthias Beckmann ◽  
Arndt Hartmann ◽  
...  

Abstract Introduction This study investigated subfertile patients with abnormally thin endometrium after infertility treatment. As they had adequate serum concentrations of hormones, an endometrial factor for subfertility was suspected. Methods To elucidate the cause of subfertility, endometrial biopsies were taken in each patient in the late proliferative and mid-secretory phases of one menstrual cycle. Endometrial biopsies from women with normal menstrual cycles and confirmed fertility who were undergoing hysterectomy for benign uterine disease were used as positive controls. The tissue samples were investigated for steroid hormone receptor expression and for the proliferation marker Ki-67. Immunohistochemistry was performed with antibodies against the marker molecules for endometrial receptivity – β3 integrin, VEGF, LIF, and CD56 (large granular lymphocytes, LGLs). Results The steroid hormone receptors for estrogen (E2) and progesterone (P) were expressed normally (at the first biopsy) and were down-regulated (at the second biopsy) within the cycle. Strikingly, all of the marker molecules investigated showed negative or weak and inadequate expression in the mid-secretory phase. Numbers of LGLs remained as low as in the proliferative phase. In contrast, fertile patients were found to express these marker molecules distinctly in the mid-secretory phase. Conclusions It may be hypothesized that a severe deficiency of these angiogenesis-related marker molecules leads to defective development of the endometrium, which remains thin. Deficient angiogenetic development may thus provide an explanation for the endometrial factor that causes infertility. Further investigations will need to focus on identifying the regulating factors that act between steroid receptor activation and the expression of these marker molecules.


1979 ◽  
Vol 92 (3) ◽  
pp. 547-552 ◽  
Author(s):  
B. Kreitmann ◽  
F. Bayard

ABSTRACT The concentrations of endometrial oestrogen and progesterone receptors, both in cytosol and in nuclei, have been studied at 8–10 weeks and at 38–40 weeks of gestation. At these two periods the concentration of oestrogen receptors is comparable with the concentration observed during the late secretory phase of the menstrual cycle. At 8–10 weeks of gestation, concentration of progesterone receptors is also comparable with the concentration observed during the secretory phase of the menstrual cycle, but at term there is a significant increase (P < 0.05) and the concentration is then comparable with the concentration observed in the pre-ovulatory period of the menstrual cycle. The receptor binding sites are always predominantly found in nuclei and the increase in progesterone nuclear receptor at term suggests that in man the progesterone withdrawal is not a necessary step in the mechanism of uterine activation during parturition as it is in other species.


2003 ◽  
Vol 178 (3) ◽  
pp. 357-372 ◽  
Author(s):  
B Gellersen ◽  
J Brosens

During the menstrual cycle, the ovarian hormones oestradiol and progesterone control the ordered growth and differentiation of uterine cells. This remodelling process is critical for implantation of the developing embryo, the formation of the placenta, and maintenance of pregnancy. Failure of uterine tIssues to respond appropriately to ovarian hormone signalling results in defective placentation, associated with a spectrum of pregnancy disorders such as recurrent miscarriages and preeclampsia. These obstetrical disorders are a major cause of maternal and perinatal morbidity and mortality. Progesterone exerts its action on target cells, at least in part, through binding to the progesterone receptor (PR), a member of the steroid/thyroid hormone receptor superfamily of ligand-activated transcription factors. The mechanism by which progesterone controls the differentiation of human endometrial stromal cells, a process termed decidualization, in the secretory phase of the menstrual cycle is not well understood. Emerging evidence indicates that locally expressed factors and activation of the cAMP second messenger pathway integrate hormonal inputs and confer cellular specificity to progesterone action through the induction of diverse transcription factors capable of modulating PR function.


1978 ◽  
Vol 77 (3) ◽  
pp. 361-371 ◽  
Author(s):  
J. B. MAATHUIS ◽  
R. W. KELLY

The concentrations of prostaglandins F2α (PGF) and E2 (PGE) were measured by gas chromatography–mass spectrometry in endometrial tissue obtained from 45 normal women at various stages of the menstrual cycle. During the proliferative stages, the concentration of PGF in the endometrium was correlated with the concentration of oestradiol in the plasma. The concentration of PGF during the mid-secretory stage (mean, 2·047, range, 0·549–4·344 μg/g fresh endometrial tissue) was significantly higher than the concentrations during the late proliferative and late secretory stages. The endometrial concentration of PGE did not show a cyclic variation. The concentrations of PGF and PGE in samples of endometrium collected after the administration of clomiphene were significantly lower than the concentrations observed in endometrial tissue obtained from normally menstruating women in the mid-proliferative period. The administration of an oestrogen–progestogen pill resulted in higher endometrial concentrations of PGE than were measured in the mid-secretory phase. The concentrations of PGF and PGE in decidual tissue (conceptual age 3–10 weeks) were lower than those measured at any stage of the normal menstrual cycle. During the human menstrual cycle, high levels of oestradiol and progesterone are related to high endometrial levels of PGF but not PGE. The presence of a conceptus apparently blocks the effect of high concentrations of ovarian steroids on the synthesis or catabolism of prostaglandins.


Author(s):  
Joachim Alfer ◽  
Roxana M. Popovici ◽  
Amir Fattahi ◽  
Jürgen Krieg ◽  
Ralf Dittrich ◽  
...  

Abstract Purpose Limited information is clinically available concerning endometrial receptivity; assessing endometrial transformation status is therefore an urgent topic in assisted reproductive technology. This study aimed to investigate individual endometrial transformation rates during the secretory phase in subfertile patients using personal endometrial transformation analysis. Methods Monitoring was carried out during the secretory phase to obtain endometrial receptivity profiles. For the investigation, two endometrial biopsies were taken within one menstrual cycle. The extended endometrial dating was based on the Noyes criteria, combined with immunohistochemical analyses of hormone receptors and proliferation marker Ki-67. Biopsies were taken mainly at days ovulation (OV, n = 76)/hormone replacement therapy (HRT, n = 58) + 5 and + 10. Results The results of the two biopsies were correlated with the clinically expected day of the cycle and showed temporal delays or hypercompensations, diverging from the expected cycle days by 0.5–5 days. In comparison with the first biopsies, the transformation rate in the second biopsies showed compensation, augmented delay, or constant transformation in 48.69, 22.37, and 28.94% of cases for ovulation in natural cycles and 56.89, 25.85, and 17.26% for HRT cycles, respectively. Conclusion The study revealed an individually dynamic transformation process of the endometrium, with the ability to compensate or enlarge an initial “delay”, which is now identified as a normal individual transformation process during the secretory phase. This information is of great importance for the scientific investigation of dynamic changes in endometrial tissue, as well as for the timing of embryo transfers.


2020 ◽  
Vol 17 (2) ◽  
pp. 187-192
Author(s):  
E.A. Novikova ◽  
◽  
O.V. Kostromina ◽  
D.V. Mikhailov ◽  
S.L. Leontiev ◽  
...  

Aim. The aim of the study was to determine the presence of peculiarities of the age structure in patients with various surrogate molecular biological subtypes of breast cancer. Materials and research methods. This work analyzes the age-related characteristics of the occurrence of molecular biological subtypes in 499 patients with invasive breast cancer. All cases were divided into 5 molecular biological subtypes based on immunohistochemical studies of hormone receptors, Her2, Ki-67. The average age of the patients was 53.4±0.39 years, the predominant group was patients from 50 to 60 years (37.2% of the total). Research results. In patients under 40 years old, the triple negative subtype prevailed (44.8%). Luminal A subtype prevailed in the groups 51-60 years old (more than 41.4%) and over 60 years old (39.7%). Luminal B (Her2-) subtype was equally found in all age groups.


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