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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.
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Yolk sac and endometrial tissue were obtained from tammar wallabies between 11 and 25 days after the removal of pouch young. Tissues were examined histologically and steroid-metabolizing enzymes were identified by incubation for 3 h at 37 °C in Medium 199 containing labelled steroid precursors. Yolk sac membrane (YSM) incubated with labelled pregnenolone produced a small amount of progesterone and pregnanediols; 80·5 ± 8·4 (s.e.m.) % of the original substrate remained unmetabolized. Labelled androstenedione was metabolized to 5α-androstane-3,17-dione and androsterone, and only 5·8 ± 3·8% of the original substrate remained at the end of incubation. Incorporation of androstenedione or dehydroepiandrosterone (DHA) into phenolic compounds was low (0·5 ± 0·1%). There was no evidence for the enzymes, arylsulphatase or sulphotransferase, in YSM. Endometrial tissue from the same animals metabolized pregnenolone, DHA and androstenedione, converted progesterone to androstenedione, and produced aqueous-soluble steroid conjugates. The results demonstrated that YSM contains enzymes associated predominantly with steroid catabolism and with incipient progesterone synthesis. The findings are discussed in relation to the histological appearance of the tissues and compared with placental steroid synthesis in eutherian mammals.
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ABSTRACT
The inhibition of endometrial phospholipase A2 activity by the non-steroidal anti-inflammatory agents mefenamic acid and indomethacin was studied over the concentration range 1 mmol/l–0·1 μmol/l. Both phospholipase A2 type 1 (a calcium-dependent enzyme) and phospholipase A2 type 2 (a calciumindependent enzyme) were inhibited by mefenamic acid, but the magnitude of the inhibition was dependent on calcium concentration. Phospholipase A2 type 1 was inhibited 50% by 10 μmol mefenamic acid/1 in the presence of 1·25–5 mmol calcium/l, but a concentration of 2·2 mmol mefenamic acid/l was required for 50% inhibition in the absence of calcium. On the other hand, phospholipase A2 type 2 was inhibited 50% by 22 μmol mefenamic acid/1 in the absence of calcium and by 100 μmol mefenamic acid/l in the presence of calcium (2·5 mmol/l). Although indomethacin was a less effective inhibitor of phospholipase A2 activity, a similar relationship with calcium was demonstrated. However, indomethacin also had a stimulatory effect on phospholipase A2 type 1 activity in the absence of calcium. Our findings suggest that the two endometrial enzymes may be inhibited by different mechanisms and that the dependence of the enzyme on calcium for activation may be a contributing factor.
J. Endocr. (1988) 119, 141–145
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ABSTRACT
Patterns of induced protein synthesis and secretion in guinea-pig endometrial epithelial cell cultures in response to oestrone sulphate alone and oestrone sulphate plus progesterone were investigated. Epithelial cells were cultured for 3 days in growth medium, then washed three times in a steroid-free medium. For each experiment, anticytokeratin immunostaining was used to discriminate the epithelial cells from the stromal cells. Only experiments in which the control dishes displayed more than 80% of anticytokeratinimmunostained cells were further processed. After this period oestradiol-17β (20 nmol/l; control), oestradiol-17β (20 nmol/l) plus progesterone (0·5 μmol/l), oestrone sulphate (1 μmol/l) or oestrone sulphate (1 μmol/l) plus progesterone (0·5 μmol/l) were added to the medium for 48 h. An immunocytochemical progesterone receptor assay showed that oestradiol-17β increased the progesterone receptor content of cells, and progesterone added to cultured cells in the presence of oestradiol-17β induced a significant increase in oestrogen sulphotransferase activity assessing the hormone responsiveness of the cultured cells.
In these culture conditions and after 16 h of incubation, oestradiol-17β induced a 1·7-fold increase in [3H]thymidine incorporation into DNA, and [35S]methionine incorporation into cellular proteins was linearly increased up to 8 h. Biochemical changes induced by the different hormone treatments were studied by labelling the proteins with a 6-h pulse of [35S]methionine. The proteins present in the medium and in cells were analysed by two-dimensional polyacrylamide gel electrophoresis, followed by fluorography. Addition of oestrone sulphate alone or with progesterone produced a change in the patterns of cellular and secreted proteins compared with those in cells cultured with either oestradiol-17β or oestradiol-17β plus progesterone. Three cellular proteins (M r < 14 000, isoelectric point (pI) 5·2 and 5·3; M r 75 000, pI 4·9) and one secreted protein (M r 155 000, pI 5·6–5·9) were specifically induced and could serve as markers of oestrone sulphate action.
Journal of Endocrinology (1989) 123, 233–241
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The intensity of the reaction for the enzyme alkaline phosphatase in the uterine epithelial cells is increased by oestrogen in the mouse (Atkinson & Elftman, 1946), monkey (Atkinson & Engle, 1947) and rat (Pritchard, 1949). Reports of the influence of progesterone on the response to oestrogen are conflicting. Administered to the intact rat during pro-oestrus it reduces the alkaline phosphatase reaction (Pritchard, 1949), and similarly when given concurrently with oestrogen in the monkey causes a reduction in the response (Atkinson & Engle, 1947). In the mouse, Atkinson & Elftman (1946) report that progesterone does not affect the response to oestradiol. Their conclusions, however, are based on experiments using very large doses of oestradiol (daily injection of 1 μg. oestradiol benzoate for 3 days) which may not reproduce a uterine reaction found in any physiological situation. The present experiments were undertaken to study the effect of progesterone on the distribution and
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A cytosolic oestrogen receptor from baboon endometria was detected and partially characterized. The apparent dissociation constant for oestradiol was 1·5 × 10−10–4 × 10−10 mol/l. Steroids that competed with the [3H]oestradiol binding to the receptor were oestradiol and ethynyloestradiol > oestriol > oestrone; progesterone, testosterone and corticosterone were not competitors. The [3H]oestradiol–receptor complexes migrated as a 3–3·5S peak during sucrose density-gradient centrifugation when endometrial samples were taken during either the proliferative or the secretory phase. A 7S peak was observed for samples taken at the period of ovulation. A [3H]oestradiol exchange technique was used to detect changes in the receptor concentration during the menstrual cycle. This concentration which was high during the early follicular phase fell sharply before the ovulatory peak of ovarian oestrogens. It remained at a base level during the early secretory phase and then rose during the last days of the cycle to the same concentration as that measured at the beginning of the cycle.
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Introduction The human endometrium is a dynamic tissue that lines the uterine cavity. It is composed of both epithelial and stromal cells and is cyclically regenerated. The reproductive cycle in human females is driven through neuroendocrine
Department of Human Pathology and Oncology, University of Siena, Policlinico ‘Le Scotte’ Viale Bracci, 53100 Siena, Italy
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Department of Human Pathology and Oncology, University of Siena, Policlinico ‘Le Scotte’ Viale Bracci, 53100 Siena, Italy
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Department of Human Pathology and Oncology, University of Siena, Policlinico ‘Le Scotte’ Viale Bracci, 53100 Siena, Italy
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Department of Human Pathology and Oncology, University of Siena, Policlinico ‘Le Scotte’ Viale Bracci, 53100 Siena, Italy
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Department of Human Pathology and Oncology, University of Siena, Policlinico ‘Le Scotte’ Viale Bracci, 53100 Siena, Italy
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Department of Human Pathology and Oncology, University of Siena, Policlinico ‘Le Scotte’ Viale Bracci, 53100 Siena, Italy
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Department of Human Pathology and Oncology, University of Siena, Policlinico ‘Le Scotte’ Viale Bracci, 53100 Siena, Italy
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Department of Human Pathology and Oncology, University of Siena, Policlinico ‘Le Scotte’ Viale Bracci, 53100 Siena, Italy
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Department of Human Pathology and Oncology, University of Siena, Policlinico ‘Le Scotte’ Viale Bracci, 53100 Siena, Italy
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Department of Human Pathology and Oncology, University of Siena, Policlinico ‘Le Scotte’ Viale Bracci, 53100 Siena, Italy
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Department of Human Pathology and Oncology, University of Siena, Policlinico ‘Le Scotte’ Viale Bracci, 53100 Siena, Italy
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Introduction The human endometrium expresses several peptides/proteins that are believed to participate in the paracrine signaling to other cell types during the menstrual cycle and in early pregnancy, and dysfunction in synthesis
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SUMMARY
Twenty-five endometrial carcinomas and three non-endometrial carcinomas were studied for the influence of various steroid hormones on the synthesis of DNA and RNA in short-term incubations in vitro. Endometrial carcinomas showed a dose-dependent sensitivity to progesterone in vitro, the response in both nucleic acids sometimes exceeding that of normal endometria. The mean reduction in DNA synthesis was to 46% and in RNA synthesis to 39% of the control values. Poorly differentiated carcinomas showed higher values of DNA synthesis than highly differentiated ones, as did carcinomas from younger women compared with those from older women. The response in vitro to progesterone was not correlated with these factors. Pregnenolone and a synthetic progestogen were less effective in vitro than progesterone. Oestradiol at a high concentration (20 μg/ml) in some cases significantly reduced the synthesis of both nucleic acids, possibly because of a specific 'toxic' action on the cells. No hormonal effects were observed in non-endometrial carcinomas.
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SUMMARY
The succinic dehydrogenase (SDHase) and adenosinetriphosphatase (ATPase) activities were determined in the corpora lutea, ovarian interstitial tissue and endometria of pseudopregnant (PP) rabbits and rabbits in which superovulation was produced by treatment with pituitary gonadotrophins (SO). Statistical analysis of the results showed that the weight, SDHase, ATPase and percentage solids of the corpora lutea, and the SDHase of the endometria of each of the two groups varied significantly (P<0·01) between days. The day values for the SDHase of the endometria, however, were particularly high in SO rabbits at the 2-day stage and low in the 12- to 16-day stages as compared with the PP group. Other differences found were of less statistical significance.
The results are considered in relation to the poor survival of embryos formed from eggs of SO rabbits. The lesser weight of the corpora lutea and the lesser SDHase activity of the endometria of the SO group, as compared with the PP group during the latter half of the experimental period, may be significant in relation to the poorer survival of embryos.
