Late Secretory Stage Research Articles

SEM Study of the Development of Rat Incisor Enamel Hypoplasia Under Hypocalcemia Induced by Thyro-Parathyroidectomy

Several clinical studies have reported the presence of enamel hypoplasia in congenital hypoparathyroidism or hypocalcemia. In previous studies we showed that thyro-parathyroidectomy (TPTX) induced perturbations of the ameloblast morphology and secretion, of the rod pattern and of the enamel surface at late secretory stage and beginning of maturation, and limited hypoplasia in the erupted enamel of rat incisor. The aim of the present study was to evaluate by SEM, the extent and evolution of the enamel alterations of thyro-parathyroidectomized rats during the maturation stage. Wistar rats were thyro-parathyroidectomized and sacrificed 57 days later. The incisors were dissected out and processed for SEM. The surface of the incisor was observed from the end of secretion/beginning of maturation to its incisal erupted end. Transverse sections were prepared to study the structural defects and the prism pattern at different stages. The results showed that the surface of the TPTX incisors presented large hypoplastic defects at the end of secretion/beginning of maturation and only small defects in the erupted part. Transverse sections showed that, at the transition from secretion to maturation, the enamel defects extended to the mid-thickness of the tissue. At the incisal end the defects were limited to the outer enamel. As it is difficult to understand how the large apical defects could recover to appear as small hypoplasia at the incisal end, these results raise new questions concerning: (1) the effect of a long term calcium deficiency upon the cellular activity of the ameloblasts, and (2) the capacity of the enamel organ to compensate structural abnormalities.

Genomic Imprinting and the Endometrial Cycle

H19 is an imprinted maternally expressed gene, which is not translated to protein and functions as an RNA molecule. It is closely related to the oppositely imprinted paternally expressed insulin-like growth factor 2 (IGF-2). While the biological function of H19 is not understood IGF-2 is a growth factor that plays a role in human follicular and endometrial differentiation. We examined the expression of H19 in the endometrium and ovary during the menstrual cycle by in situ hybridization applied to paraffin sections of human endometrium and ovaries at different stages of differentiation. In the endometrium, H19 expression was confined to the stroma and fluctuated with endometrial dating to reach its peak in the late secretory stage. IGF-2 was also prominently expressed in late secretory endometrium, but its expression was evident both in the stroma and glandular epithelium. Expression of H19 was not found in primordial, primary, and preantral follicles of the ovary, but prominent expression was evident in the theca of antral and cystic atretic follicles, and focal expression was noted in the granulosa of corpora lutea. An association between H19 expression during the menstrual cycle and the differentiation state of the human female reproductive tract, which is under hormonal control, is suggested.

Recent observations on enamel crystal formation during mammalian amelogenesis.

Enamel mineralization taking place during amelogenesis is a unique model to investigate carbonatoapatite formation in vivo. The abundance of proteinaceous crystal growth inhibitors, in particular amelogenins, contributes significantly to the mineralization process. Their putative roles are to prevent random proliferation of crystal nuclei and to regulate the growth kinetics and orientation of the formed enamel crystals. The enamel fluid surrounding the forming enamel crystals contains high concentrations of carbonate and magnesium ions, both of which seem to modulate the mineralization process. Particularly, Mg ions can adsorb onto enamel crystal surfaces in a manner to compete with Ca ions. Enamel mineral formed during amelogenesis is featured as calcium-deficient, acid phosphate-rich carbonatoapatites. Currently the most putative stoichiometry model for enamel mineral is (Ca)5-x(HPO4)v(CO3)w(PO4)3-x (OH)1-x. Very significant changes in the morphology, stoichiometry, and solubility of enamel crystals occur during the various stages of amelogenesis. The early enamel mineralization comprises two events: the initial precipitation of the well-documented thin ribbons and the subsequent overgrowth of apatite crystals on those templates. The thin ribbons precipitated in the vicinity of the secretory ameloblasts have the highest contents of acid phosphate, particularly in the form of exchangeable species, whereas both the exchangeable and unexchangeable acid phosphate decrease concomitantly with the progress of the apatite overgrowth and the appearance of elongated hexagonal crystals in the late secretory stages. Those morphological and compositional features seem to be consistent with the formation of precursors, such as octacalcium phosphate.

Regulated expression of cadherin-11 in human epithelial cells: a role for cadherin-11 in trophoblast-endometrium interactions?

Cadherin-11 is a novel member of the cadherin supergene family. Cadherin-11 expression is localized to mesenchymal tissue and specific regions of the neural tube during mouse embryogenesis. Here we report that cadherin-11 is spatiotemporally expressed in the epithelial cells of the human placenta. Cadherin-11 mRNA levels were low in freshly isolated cytotrophoblast cells but increased as the cytotrophoblast cells aggregated and fused to form syncytiotrophoblast cells in vitro. The increase in cadherin-11 mRNA levels was concomitant with a decrease in E-cadherin expression. Cadherin-11 was localized to the syncytial trophoblast and extravillous cytotrophoblasts, but not the villous cytotrophoblasts of the human placenta by immunohistochemistry. As both of the former cell types have intimate interactions with the endometrium, we examined cadherin-11 expression in the human endometrium. Cadherin-11 was detected in the glandular and surface epithelium of the endometrium at all stages of the menstrual cycle. However, cadherin-11 was abundant only in the stroma in the late secretory stage of the menstrual cycle. The accumulation of cadherin-11 in the stroma correlated with decidualization. Taken together, our observations demonstrate that cadherin-11 is expressed in certain epithelial cell lineages and suggest the possibility that cadherin-11 plays an important role in mediating trophoblast-endometrium interactions.

Regulated expression of cadherin‐11 in human epithelial cells: A role for cadherin‐11 in trophoblast‐endometrium interactions?

Cadherin-11 is a novel member of the cadherin supergene family. Cadherin-11 expression is localized to mesenchymal tissue and specific regions of the neural tube during mouse embryogenesis. Here we report that cadherin-11 is spatiotemporally expressed in the epithelial cells of the human placenta. Cadherin-11 mRNA levels were low in freshly isolated cytotrophoblast cells but increased as the cytotrophoblast cells aggregated and fused to form syncytiotrophoblast cells in vitro. The increase in cadherin-11 mRNA levels was concomitant with a decrease in E-cadherin expression. Cadherin-11 was localized to the syncytial trophoblast and extravillous cytotrophoblasts, but not the villous cytotrophoblasts of the human placenta by immunohistochemistry. As both of the former cell types have intimate interactions with the endometrium, we examined cadherin-11 expression in the human endometrium. Cadherin-11 was detected in the glandular and surface epithelium of the endometrium at all stages of the menstrual cycle. However, cadherin-11 was abundant only in the stroma in the late secretory stage of the menstrual cycle. The accumulation of cadherin-11 in the stroma correlated with decidualization. Taken together, our observations demonstrate that cadherin-11 is expressed in certain epithelial cell lineages and suggest the possibility that cadherin-11 plays an important role in mediating trophoblast-endometrium interactions. © 1996 Wiley-Liss, Inc.

Nuclear DNA fragmentation during postnatal tooth development of mouse and hamster and during dentin repair in the rat.

The TUNEL (transferase-mediated, dUTP-biotin nick end labeling) method for in situ labeling of DNA strands was utilized to localize DNA fragmentation in cells involved in tooth formation in the neonatal mouse and hamster. Positive reactions for the presence of DNA fragments were obtained in some epithelial cells of the cervical loop region of incisors, late secretory, transitional and early maturation stage ameloblasts, stratum intermedium cells and in shortened ameloblasts just before eruption. Also, cells of the periodontal ligament of the continuously erupting incisors stained positive shortly before eruption. Odontoblasts were negative but became strongly positive during the formation of physiological osteodentin at the tip of developing incisors. Osteodentin matrix and the surfaces of unerupted enamel and cementum just prior to eruption stained for DNA fragments as well. DNA fragmentation could be elicited in odontoblasts and underlying pulpal tissues of mature erupted molars after mechanical injury to the odontoblast processes during cavity preparation. We conclude that, in rodents, DNA fragmentation and cell death are biological processes which take place in a variety of cells involved in formation of teeth. The TUNEL staining technique is a simple but powerful tool to examine the fate of cells and tissues undergoing either programmed cell death (apoptosis) or fragmentation of nuclear DNA induced by external factors leading to pathological changes.

Vascular smooth muscle alpha-actin distribution around endometrial arterioles during the menstrual cycle: increased expression during the perimenopause and lack of correlation with menorrhagia.

Menorrhagia affects approximately 9% of all women, increasing to 20% during the perimenopause. The majority of menstrual loss occurs through the spiral arterioles - specialized endometrial vessels that are intimately involved in controlling menstruation. Our aim was to compare the distribution of vascular smooth muscle alpha-actin using immunohistochemical techniques in the endometrium of women before and during the perimenopause and with or without menorrhagia. We hypothesized that differences in vessel numbers and types exhibiting alpha-actin staining would exist between these groups, reflecting structural/functional differences. The results showed that perimenopausal menorrhagic women had significantly more smooth muscle alpha-actin expression than non-perimenopausal controls in four out of five menstrual cycle stages (P < 0.05), while perimenopausal non-menorrhagic women demonstrated a significant increase at the mid-proliferative stage only (P < 0.007). No significant differences occurred between women with or without menorrhagia before or during the perimenopause. Perimenopausal women had significantly more straight arterioles (P < 0.02) than women prior to perimenopause at the late secretory stage, while non-perimenopausal women demonstrated significantly higher numbers of spiral arterioles (P < 0.002) in the early secretory stage, although this difference had disappeared by the late secretory stage. In conclusion, we found no major differences in endometrial vascular smooth muscle alpha-actin staining between women with and without menorrhagia, but significant increases in alpha-actin staining in women showing perimenopausal symptoms.

Evidence for oestrogenic regulation of heat shock protein expression in human endometrium and steroid-responsive cell lines

Gene amplification with target-specific primers (reverse-transcription polymerase chain reaction (RT-PCR)) was used to monitor the relative expression of oestrogen and progesterone receptor mRNAs alongside the mRNAs for heat shock proteins HSP 90 alpha, HSP 90 beta and HSP 70a in normal samples of human endometrial tissue over the whole menstrual cycle and in short-term cultures of steroid-responsive (T47-D) and unresponsive (HRT-18) cell lines exposed to oestradiol and progesterone over a 24-h incubation period. In endometrium, oestrogen and progesterone receptors followed the expected patterns of expression at the protein level during the menstrual cycle and also showed a positive correlation of expression with each other throughout (r = 0.514). Of the HSPs only HSP 90 alpha expression correlated positively with oestrogen receptor (r = 0.687), while HSP 70a expression, which peaked in the late secretory stage, displayed a significantly inverse correlation with HSP 90 beta expression (r = -0.526). All p values < 0.05. In T47-D cell cultures, oestrogen receptor expression was stimulated transiently by oestradiol (10(-7) mol/l) and more persistently by progesterone (10(-7) mol/l). Progesterone receptor expression was depressed by progesterone and weakly stimulated by oestradiol. HSP 70a and HSP 90 alpha expression were stimulated by oestradiol. Progesterone generally depressed HSP 90 alpha expression and simultaneous addition of both oestradiol and progesterone to the culture medium was antagonistic to HSP 90 alpha expression. No clear effect of agonist addition on HSP mRNA expression was apparent in the HRT-18 cultures. A possible mechanism for observed oestrogenic effects on HSP expression is put forward.

Morphological study of changes in the baboon oviductal epithelium during the menstrual cycle.

Oviductal epithelium of the baboon, Papio cynocephalus, was studied utilizing light, scanning, and transmission electron microscopy. Results of counts made of nonciliated, ciliated, and ciliogenic cells were analyzed statistically. The percentages of nonciliated cells of the fimbria and ampulla during the early proliferative and late secretory stages of the menstrual cycle were significantly greater than those during the mid-proliferative and late proliferative-early secretory stages, due to deciliation. This paper emphasizes previously unreported apical surface morphology as viewed by scanning and transmission electron microscopy. The microvillar pattern of the fimbrial secretory cells differs from that of the ampullar and isthmic cells in that the microvilli originate from thick apical protrusions and vary greatly in length and number as related to the cycle. A ridge demarcating the apical intercellular junction is composed of rows of microvilli during the early proliferative and late secretory stages. During the early proliferative and late secretory stages an increased degree of invagination of the basal and lateral plasma membranes occurs as the height and width of the cells decreases. The general numbers and distribution of the organelles of the various types of oviductal cells agree with that described for the ampulla and isthmus by Verhage et al. [(1990) Am. J. Anat., 187:81-90]; however, fimbrial epithelium was not included in that study. Other cyclic ultrastructural changes not examined previously include variation in the number of lipid droplets and their location, and in the number and relationships of glycogen particles to other structures.

Expression of mRNA for keratinocyte growth factor and its receptor in human endometrium.

The aim of the present study was to evaluate the expression of mRNA for the keratinocyte growth factor and the keratinocyte growth factor receptor in human endometrium at different stages of the menstrual cycle. The role of estrogen and progesterone in regulating the expression of the mRNAs encoding keratinocyte growth factor and its receptor was further examined by studying the effect of continuous progestin (endometrium exposed to levonorgestrel releasing intrauterine contraceptive device), and continuous estrogen (endometrium hyperplasia) on the endometrium. The expression of mRNA in endometrial samples was evaluated using reverse transcriptase polymerase chain reaction. The expression of KGF mRNA was found to vary during the menstrual cycle, with the highest levels in the progesterone-dominated late-secretory stage endometrium. Keratinocyte growth factor mRNA expression was low in both the endometrium that had been under the influence of continuous progestin (atrophic endometrium) and continuous estrogen (hyperplastic endometrium). The highest level of keratinocyte growth factor receptor mRNA expression was seen in late-proliferative stage of the menstrual cycle and in hyperplasia when the estrogen exposure to endometrium is high. A low receptor mRNA level was found in endometrium exposed to continuous progestin. The results suggest that keratinocyte growth factor mRNA expression is progesterone dependent, whereas keratinocyte growth factor receptor mRNA expression seems to be more estrogen than progesterone dependent.

Physiology: Immunohistochemical characterization of human endometrial microvascular basement membrane components during the normal menstrual cycle

The expression of three basement membrane components [collagen IV (CIV), laminin and heparan sulphate proteoglycan (HSPG)] and platelet endothelial cell adhesion molecule (PECAM) were examined by immunohistochemistry in cryostat sections of normal human endometrium. Alkaline phosphatase (ALP) was detected using enzyme histochemistry. Endometrial biopsies from the menstrual (n = 4), mid-late proliferative (n = 5), early-mid secretory (n = 5) and late secretory (n = 5) stages were collected from women with a normal menstrual cycle. At all four stages of the menstrual cycle, CIV, laminin and HSPG were expressed on basement membranes of both vessels and glands whilst PECAM expression was localized specifically to endothelial cells. A similar number of vessels/mm2 stained for CIV and laminin, as well as for PECAM at each stage of the menstrual cycle, demonstrating that all vessels in endometrium stain for these two basement membrane components. By contrast, the number of vessels/mm2 that stained positively for HSPG and ALP was significantly lower, averaging approximately 55% of the total that stained positively for PECAM, CIV and laminin. During the menstrual stage, HSPG staining intensity remained strong in glandular basement membranes but decreased dramatically in vascular basement membranes. ALP activity was variable in both the vessels and glands throughout the four stages of the menstrual cycle studied. This study demonstrates heterogeneity in basement membrane components within the endometrial microvasculature. It is postulated that the disappearance of HSPG from vascular basement membranes may play a role in the process of vascular remodelling during the menstrual stage of the cycle.

Yeast ts secretory mutation rgs1 is suppressed by the SEC4 gene of Saccharomyces cerevisiae.

Yeast rgs1 cells accumulate secretory vesicles in the cytoplasm and stop the secretion of proteins at the restrictive temperature. The ts mutation rgs1 may be suppressed by several different genes; the S. cerevisiae SEC4 gene, encoding the small G-protein involved in the late secretory stage, is one of them. Synthetic lethality of the double rgs1 sec4 mutant is demonstrated.

Immunolocalization of enamel proteins during amelogenesis in the cat.

Amelogenesis in the cat has been suggested to closely resemble enamel formation in human teeth. In order to further characterize the sequence of events leading to enamel formation in the cat, the expression and distribution of enamel proteins throughout amelogenesis were examined by postembedding immunocytochemistry using an antibody to mouse amelogenins and the high resolution protein A-gold technique. Enamel proteins were first immunodetected in ameloblasts and in the extracellular matrix during the presecretory stage. Secretory stage ameloblasts showed the most intense cellular reactivity. In these cells, protein synthetic organelles, secretory granules, and large lysosome-like structures were all intensely labeled. Extracellularly, numerous gold particles were observed over enamel and over patches of material found at the baso-lateral surfaces of these ameloblasts. During the early maturation stage, the protein synthetic organelles and secretory granules of ameloblasts still showed some immunoreactivity, although the most conspicuous labeling at this later stage was found over enamel and over material present among the extensive apical membrane infoldings of ruffle-ended ameloblasts. Qualitative analysis of lysosome-like elements in ameloblasts suggested that their frequency and immunoreactivity in the maturation stage were relatively lower than in the secretory stage, where some groups of cells often showed numerous large labeled structures. The enamel matrix was intensely labeled at all stages; however, cervical-occlusal and surface-depth gradients were readily apparent by conventional staining and by quantitative analysis of immunolabeling in the late secretory and early maturation stages. These data suggest that the cellular and extracellular distribution of enamel proteins in the cat is generally similar to that reported in other species, although some particularities were observed, perhaps reflecting variation in the timing of developmental parameters.

Properties of phosphorylated 32 kd nonamelogenin proteins isolated from porcine secretory enamel

Enamel proteins were isolated from specific locations of permanent porcine incisors at various developmental stages, namely, the outer (young) and inner (old) secretory, and maturing (chalk-like in appearance) enamel. The selective adsorption of these matrix proteins onto hydroxyapatite (HA) crystals was investigated in the presence of dissociative agents. The results showed that the proteins with the highest adsorption affinity were present at the highest concentration in the vicinity of the ameloblasts, i.e., in the outer enamel layer; a substantial reduction of these proteins was observed in the older (inner) secretory enamel and in the tissue in the maturing stage. An interesting finding was that a group of proteins having molecular masses of 32 kd present only in the inner secretory enamel, adsorbed strongly onto the HA crystals and were potent inhibitors of HA crystal growth. This 32 kd group contains phosphorylated glycoproteins; they are rich in Pro, Glu, Gly, and Asp and the N-terminal sequence was LXQVPGRIPPGYGRPPTP-, having no resemblance to the reported sequences of amelogenins. It was also found that the 32 kd moieties remained only as trace constituents in the maturing enamel, suggesting that most of them were removed as soluble constituents in the tissue fluid or further degraded by enzymatic activity during the late secretory stage. The results obtained support the view that amelogenetic mineralization is regulated by the presence of various organic matter and, importantly, that their efficacy as inhibitors of mineralization may be modulated through their degradation.

Tetracycline as a marker in hard tissue research: effects on enamel formation in rat maxillary incisors.

Tetracycline in low dose is often used as a marker in hard tissue research. A low dose effect on enamel formation has never been proven despite well known toxic reactions in enamel after higher doses. The purpose of the investigation was to evaluate enamel formation in maxillary incisors of rats given a single low dose of a tetracycline with low toxicity, commonly used in research. Eight young rats received an intraperitoneal injection of 2 mg oxytetracycline per 100 g. The rats were terminated after periods between 1 h until 5 days. Undemineralized ground sections were prepared and studied under fluorescence microscopy. Microradiograms were taken to study the degree of mineralization. A diffuse uptake was seen within enamel in areas corresponding to late secretory stage and incisally in maturing enamel with a low mineralization degree. Tendencies of enamel aberrations were seen in all rats. These appeared as splittings within the formed enamel. In conclusion, low toxicity tetracycline disturbs normal amelogenesis, even if administered in low doses. It should therefore be avoided in hard tissue research where enamel formation is studied.

Effects of phosphonoformic and phosphonoacetic acids on developing enamel of rat molars

The effect of a single subcutaneous injection of different dosages of phosphonoformic or phosphonoacetic acid on the developing dental tissues of the rat molar was studied. The substances were injected at different rat ages and effects on the developing teeth were analyzed by means of histochemistry of frozen sections and scanning electron microscopy. Molars of rats injected at the age of 10 or 15 days showed no pathologic changes. Administration of phosphonoacetic acid in a dosage of 10 or 20 mg P/kg b.w. had no demonstrable effect on the dental tissues in any of the animals. Phosphonoformic or phosphonoacetic acid in a dosage of 10 or 30 mg P/kg b.w. respectively induced subameloblastic cysts 24 h after injection to 4-7-day-old rats. The cysts were mainly localized on the mesial sides of the cusps under ameloblasts in the late secretory stage. Calcified depositions were seen in the ameloblastic layer lining the cystic cavities. A thin zone, the staining of which indicated a high mineral content, was seen in the outermost enamel layer under the cysts. A few days later, enamel hypoplasias were seen in areas previously occupied by cysts. A lightly stained line was observed in the enamel matrix demarcating the amount of enamel matrix formed before and after the injection. Hypoplastic lesions were also noted in the enamel surface of newly erupted molars. These findings suggest that the two injected monophosphonates can induce pathologic changes in the developing enamel organ and hypoplasias in the enamel.

Localization of two distinct acid phosphatases in secretory ameloblasts of rat molar tooth germs

Acid phosphatases were examined histochemically at the light- and electron-microscopic levels using para-nitrophenyl phosphate (pNPP) and β-glycerophosphate (β-GP) as substrates. By light microscopy, there was intense activity with pNPP in supranuclear and distal regions of the secretory ameloblast, and moderate or slight activity respectively in those regions with β-GP. These enzyme activities were less at the late secretory stage of amelogenesis and disappeared at the transitional stage. By electron microscopy, acid phosphatase activity was seen in the trans side cisternae of the Golgi apparatus, in lysosome-like granules, and in small vesicles in the Tomes' processes. The activity with pNPP but not β-GP was also localized at the plasma membrane (proximal, lateral and distal surface). Activity with β-GP was completely inhibited by 1 mM sodium tartrate and by 1 mM NaF; activity with pNPP was inhibited by 1 mM NaF and 10 mM sodium tartrate, but not by 1 mM sodium tartrate. Thus there are at least two different acid phosphatases, one tartrate-sensitive and the other 1 mM tartrate-resistant, in the secretory ameloblast; the tartrate-resistant enzyme is plasma-membrane bound.

Changes during the menstrual cycle in cytosolic and nuclear concentrations of progestagen receptor in the human Fallopian tube.

[3H]R5020 was bound to cytosolic and nuclear samples of human Fallopian tube with high affinity and specificity. The cytoplasmic and nuclear concentrations of progestagen receptor varied, throughout the menstrual cycle, in the ampulla, isthmus and fimbria. Concentrations were higher at the late proliferative stage of the cycle than at the early proliferative and late secretory stages. A positive linear regression was observed between cytosolic and nuclear progestagen receptor concentrations and plasma oestradiol levels. A negative linear relationship was observed between cytosolic progestagen receptor concentration and plasma progesterone levels during the secretory stages of the menstrual cycle.

Estrogen responsive creatine kinase in normal and neoplastic cells

Estrogen-responsive creatine kinase (uterine estrogen-induced protein, CK-BB) activity was compared during ontogeny of the rat uterus, in the human menstrual cycle and in mouse and human mammary tumors. Between days 2 and 26 of post-natal development of rat uterus, the specific activity of creatine kinase increases 4.5-fold. The glycolytic enzymes, phosphoglycerate kinase and phosphoglycerate mutase, show no increase and pyruvate kinase activity increases 1.5-fold, during this period. Only creatine kinase BB activity was increased by estrogen administration. In human endometrium, the specific activity of creatine kinase increases in the late-secretory stage of the menstrual cycle. During the progression from hormonal dependence to independence shown by the GR mouse mammary tumor in the course of successive transplantations, the total activity of creatine kinase increases. The increase in the MM (muscle type, non-estrogcn responsive) isozyme activity of creatine kinase exceeds the increase in creatine kinase BB activity. Normal human breast and breast tumors display both creatine kinase isozymes. Preliminary evidence for in vitro estrogen responsiveness of creatine kinase, in human breast explants, raises the possibility that creatine kinase BB may be a suitable marker for assessing the hormonal dependence of human tumors.

Concentrations of prostaglandins F2alpha and E2 in the endometrium throughout the human menstrual cycle, after the administration of clomiphene or an oestrogen-progestogen pill and in early pregnancy.

The concentrations of prostaglandins F2alpha (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 microgram/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.