METABOLISM OF OESTRADIOL-17β AND OESTRONE IN THE HUMAN UTERUS

1975 ◽  
Vol 80 (4) ◽  
pp. 719-731 ◽  
Author(s):  
A. R. Krishnan ◽  
B. K. Bajaj ◽  
V. Hingorani ◽  
K. R. Laumas

ABSTRACT A study of the metabolism of oestradiol in the human endometrium and myometrium of the proliferative and secretory phases of the cycle showed that the conversion of oestradiol to oestrone by endometrium in the proliferative phase was higher than that in the secretory phase. The decreased metabolic activity of the secretory phase endometrium was attributed to the influence of progesterone on the endometrium. The metabolic conversion of oestradiol to oestrone was enhanced when pyridine nucleotides were added to the system. The conversion of oestradiol to oestrone was maximum in the cytoplasmic and nuclear fractions of the endometrium. Furthermore, the conversion of oestradiol was low in all the subcellular fractions of the myometrium as compared with the endometrial subcellular fractions. The presence of co-factors increased the metabolic conversion of oestradiol to oestrone in the subcellular fractions of the endometrium. The presence of 17β-hydroxysteroid oxidoreductase was indicated in all the subcellular fractions. A correlation was found between the amount of oestradiol and oestrone bound to the receptors in the uterus and the rate of metabolism of oestradiol in the uterus. The physiological significance of metabolism of oestradiol and the hormone action are discussed.

1973 ◽  
Vol 74 (3) ◽  
pp. 576-591 ◽  
Author(s):  
K. Murugesan ◽  
V. Hingorani ◽  
K. R. Laumas

ABSTRACT The human endometrium and the myometrium have the capacity to convert [6,7-3H]norethynodrel to norethindrone, 17α-ethynyl-3α,17β-dihydroxy-5-(10)-oestrene and two other unidentified metabolites. Under in vitro conditions, 80–90 % of 3H-norethynodrel was converted to its metabolites within 90 min. The metabolites formed were the same for both the endometrium and the myometrium. The amount of norethynodrel converted to its metabolites was more in the proliferative phase than in the secretory phase. Among the subcellular fractions of the myometrium, mitochondrial and microsomal fractions metabolised norethynodrel to norethindrone and two polar metabolites with low chromatographic mobility. In the myometrial 105 000 × g supernatant fraction, 17α-ethynyl-3α,17β-dihydroxy-5(10)-oestrene was formed in addition to norethindrone and the polar metabolites. The significance of the formation of norethindrone – a potent oral progestin as a product of the metabolism of norethynodrel and its possible action at the uterine level in the control of fertility is discussed.


2010 ◽  
Vol 22 (1) ◽  
pp. 274
Author(s):  
K. C. Choi ◽  
E. B. Jeung

The endometrium is hostile to embryo implantation except during the window of receptivity. A change in endometrial gene expression is required for the development of receptivity. The uterine calcium balance is crucial for physiological functioning, including smooth muscle contraction and embryo implantation. The location of cytoplasmic calcium-related proteins (CRP) include the calcium transporters 1 (CaT1), calbindin-D9k/-D28k (CaBP- 9k/28k), plasma membrane Ca2+-ATPase 1b (PMCA1b), sodium/calcium exchangers (NCX1), and potassium-dependent Na+/Ca2+ exchanger (NCKX3). The expressions of these CRP and their potential roles in the uterus of human during the menstrual cycle remain to be clarified. Thus, in this current study, the expression patterns of CRP were examined for their roles in the human uterus during the menstrual cycle. Human endometrial tissues were collected by curettage from women undergoing hysteroscopy for investigation of tubal patency or tubal ligation. Approval was given by the Human Ethics Committee at SCH Medical Center, Bucheon, and signed consent was obtained in every case. Human uterus (total n = 51) were divided into 3 groups: menstrual, proliferative, and secretory phase. Reverse-transcription PCR and Western blot analysis were applied to measure the level of CRP mRNA and protein, respectively. During the menstrual cycle of human, the expression levels of CaT1 mRNA and protein were increased 5-fold at proliferative phase (Days 6 to 13) compared with secretory phase in the endometrium of uterus. The expression of CaBP-28k mRNA and protein was less 2-fold during the proliferative phase (Days 6 to 13) than during the secretory phase (Days 16 to 28). However, the expressions of NCX1, NCKX3, and PMCA1b mRNA and protein were not altered during cycle, whereas the expression of CaBP-9k was not observed in the uterus of human. In addition, spatial expression of CRP was detected by immunohistochemistry Uterine CRP was abundantly localized in the cytoplasm of the luminal and glandular epithelial cells during menstrual cycle. Taken together, these results indicate that uterine CRP is abundantly expressed in the uterus, suggesting that uterine expression of CRP might be involved in reproductive function during the menstrual cycle in human.


1978 ◽  
Vol 87 (3) ◽  
pp. 632-642 ◽  
Author(s):  
Eve A. Willman ◽  
W. P. Collins

ABSTRACT The biosynthesis and metabolism of prostaglandin E2 was studied in cell-free homogenates of tissues from the uterus and foeto-placental unit using specific in vitro methods. The results show that the synthesis of prostaglandin E2 is greater in endometrial tissue from the secretory phase (53.07 ± 39.05; ng/100 mg wet tissue/h) than from the proliferative phase of the uterine cycle. Furthermore, endometrial tissue forms more of this compound than myometrium (P < 0.005). During early pregnancy, synthesis is decreased (25.10 ± 16.62); at term, myometrium produces more prostaglandin E2 than decidua. During labour, however, decidual tissue accumulates more of this compound (52.73 ± 18.04) than either myometrium (34.71 ± 13.19) or cord (28.63 ± 11.71). The catabolic enzymes are most active in the placenta and chorion, followed by the cord, myometrium, decidua and amnion, but the differences have only a slight effect on the amounts of prostaglandin E2 which remain at the end of the incubation. The results suggest a high turnover of prostaglandin E2 in the decidua, myometrium and cord.


1974 ◽  
Vol 62 (1) ◽  
pp. 109-123 ◽  
Author(s):  
R. G. GABB ◽  
G. M. STONE

SUMMARY Human endometrial and myometrial tissues were incubated in vitro with [3H]oestradiol-17β and [3H]oestrone to study the uptake and interconversion of these two steroids by the tissues. Endometrial tissue displayed a higher capacity for oestrogen interconversion than myometrial tissue and the oxidation of oestradiol-17β to oestrone was favoured, rather than the reverse reaction. A greater degree of oxidation was found in tissue taken from uteri in the secretory phase than in the proliferative phase. A study of the distribution of radiometabolites between 'soluble' and 'particulate' fractions of tissue homogenates showed that a greater proportion of the tissue radioactivity was associated with the 'particulate' fraction in the proliferative phase than in the secretory phase. After incubation of endometrial tissue from the secretory phase with tritiated oestrogens there was evidence of the formation of chloroform-insoluble radiometabolites and some of these were tentatively identified as oestrogen sulphates. In a second experiment, the uptake and metabolism of the same two oestrogens by tissue from leiomyomata uteri (fibroids) and normal myometrial tissue were compared. No significant difference between these tissues was found. The results suggest that the levels of 17β-hydroxysteroid dehydrogenase in the human uterus may be dependent upon the levels of oestrogens in the blood. The lack of a difference in the treatment of oestrogens by fibroid and normal myometrial tissue suggests that these tissues may have a similar mechanism for the uptake and retention of oestrogens.


2005 ◽  
Vol 17 (9) ◽  
pp. 95
Author(s):  
A. P. Ponnampalam ◽  
P. A. W. Rogers

In a previous study investigating global gene expression throughout the menstrual cycle,1 Annexin 4 (ANXIV) was identified as having significant cyclic changes in human endometrium. ANXIV belongs to a ubiquitous family of Ca2+-dependent phospholipid and membrane-binding proteins. The aims of this study were to investigate the cellular localization and regulation of ANXIV mRNA and temporal expression of ANXIV protein in human endometrium during the menstrual cycle. mRNA Expression: The menstrual cycle was divided into seven stages by histological evaluation. Curettings of endometrium were collected from 60 cycling women. For cellular localization, tissues from eight endometrial curettings were dissociated with collagenase into single cells, separated into epithelial and stromal cell fractions and snap frozen. Total RNA was extracted and ANXIV mRNA was quantified by real-time PCR. Immunohistochemistry: Full thickness endometrial tissue was collected from 50 reproductive age women undergoing hysterectomy. Tissue sections were formalin-fixed and paraffin-embedded. Goat polyclonal ANXIV antibody was used to localize ANXIV protein. ANXIV mRNA was significantly upregulated in the whole tissue during mid-late secretory phase of the cycle, and was predominantly expressed in epithelial cells. ANXIV protein was detected in the luminal and glandular epithelium in high levels throughout the menstrual cycle except in early secretory (ES) phase. The intensity of immunostaining was stronger in the glands of the basalis compared to functionalis in early proliferative phase, however, by the late secretory phase the functionalis glands showed higher expression levels. ANXIV mRNA data are consistent with a role for progesterone in upregulating the expression of ANXIV, although protein levels remain high through menstruation and into the proliferative phase. ANXIV can indirectly inhibit prostaglandin production, which is important for implantation. Hence the low levels of ANXIV protein at ES phase may relate to processes involved in implantation. (1)Ponnampalam et al. (2004). Mol. Hum. Reprod. 10(12), 879–893.


2005 ◽  
Vol 15 (3) ◽  
pp. 523-528 ◽  
Author(s):  
M. Di Paola ◽  
G. Loverro ◽  
A. M. Caringella ◽  
G. Cormio ◽  
L. Selvaggi

Under normal conditions, in human endometrium, apoptotic and antiapoptotic factors play an important role in tissue homeostasis. Abnormalities of apoptosis, a process implicated in several events in the reproductive organs, may contribute to neoplastic transformation. The present study aimed to investigate the involvement of both the receptorial and the mitochondrial pathways of apoptosis in normal endometrium and in endometrial carcinoma, by measuring caspase-3 and caspase-8 activities and cytosolic cytochrome c levels. Twelve endometrial carcinomas and nine normal endometrial specimens (four in mild proliferative phase, five in late secretory phase) were included in this study. Cytosolic fractions, obtained by differential centrifugation of tissue homogenates, were analyzed for caspase-3 and caspase-8 activities, as well as for cytochrome c content. Caspase-8 activity in normal secretory phase endometrium was higher than that in the proliferative phase and in the endometrial carcinoma. Moreover, higher cytochrome c levels were detected in endometrial carcinoma with respect to normal secretive endometrium. No significant differences were found in caspase-3 activity between normal and pathologic endometrium. The results obtained suggest that in normal endometrium, apoptosis takes place through the activation of both receptorial and mitochondrial pathways. Defects in both these pathways may contribute to the development of endometrial carcinoma.


Author(s):  
A. Gonzalez Angulo ◽  
R. Berlioz ◽  
R. Aznar

Recent ultrastructural studies on endometrial tissues from women wearing copper, wire intrauterine devices have disclosed morphological evidence of impaired glycogen degradation and secretion resulting in interference with the viability of blastocysts. Reduced microapocrine secretion observed with the scanning electron microscope supports this (1). In addition, organelle modifications have been observed in the epithelial cells of these women. The changes are seen in biopsies taken in the proliferative phase of the cycle and consist of mitochondrial vacuolation and myelin figure formation. These modifications disappear in the secretory phase and therefore have been regarded as reversible (2).The aim of the present studies was to investigate surface epithelial changes as well as organelle modifications in relation to the site of contact with an IUD that releases greater amounts of copper. Endometrial tissue was obtained from the uterine cavity of four young women wearing TCu-380-A intrauterine contraceptive devices for 4-6 weeks.


1950 ◽  
Vol 40 (1-2) ◽  
pp. 150-156 ◽  
Author(s):  
F. L. M. Dawson

The genitalia of a control series of nineteen animals, slaughtered for other reasons than reproductive failure, were studied. Of these six were in various stages of pregnancy, one was in a ‘proliferative phase’, being slaughtered probably just before the first oestrus after calving, and twelve represented different phases of the oestrous cycle, more than half exemplifying the last 4 days before heat. Stages were judged from the appearance of the ovaries, and checked in five instances by repeated rectal examinations, and observation of behaviour during life. Of the nineteen uteri eight yielded bacteria on culture, sometimes in moderately high density; from two of them, pure cultures were recovered respectively of Pseudomonas and Neisseria catarrhalis; and in another, probably Proteus was found. No previous records of these three genera at such a site have been found. Only aerobic blood agar plate cultures, and those for tuberculosis organisms were made. Dissection results unequivocally supported the view of Tagliavini in opposition to that taken by Hammond, that the sanguineous elements in post-oestral discharge originated from endometrial extravasation. The cow slaughtered 4 days after heat indicated that congestion disappears from the caruncles before leaving the areas between them. Microscopically, no mast cells, as observed by the Italian workers, could be seen; it appeared that a ‘proliferative phase’ occurs in every cycle during the three pre-oestral days, when gland tissue proliferates from its nadir of development, surface epithelium grows in height, and vascularization progresses. The rate and interrelations of these changes seemed variable. Arterioles appeared to be withdrawn from the superficial mucosa during the secretory phase. Tagliavini's claim to have observed sloughing of epithelium about the 17th day, strictly equivalent to the process of menstruation in the Primates, must on the evidence be regarded with considerable reserve.


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.


2005 ◽  
Vol 1041 (1) ◽  
pp. 136-143 ◽  
Author(s):  
COURTNEY P. BOND ◽  
LAURA J. PARRY ◽  
CHRISHAN S. SAMUEL ◽  
HELEN M. GEHRING ◽  
FIONA L. LEDERMAN ◽  
...  

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