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A Psychoyos

Publications and source records attributed to A Psychoyos.

At least 37 records · Page 2Linked to original sources

Hormonal dependence of the metrial gland: further studies on oestradiol and progesterone receptor levels in the rat.

The main objective of the present study was to analyse the hormonal dependence of the metrial gland formed in pseudopregnant animals following massive decidualization. On day 13 of pseudopregnancy (when the metrial gland reaches its maximal development) animals were ovariectomized and given s.c. implants of oestradiol and/or progesterone. A new implant technique for oestradiol delivery is described which provides circulating concentrations of oestradiol in the physiological range. In addition, we extended our previous work concerning oestradiol receptor and progesterone receptor concentrations in the metrial gland of pseudopregnant rats. The low oestradiol receptor concentration which we previously reported up to day 17 was maintained until the end of pseudopregnancy (day 21-1.5 fmol/micrograms DNA), whereas the progesterone receptor concentration remained raised (congruent to 3.5 fmol/micrograms DNA) from day 13 to day 19 and then decreased on day 21. The correlation of metrial gland weight and kinetics of the tissue oestradiol and progesterone receptors contents with the circulating oestradiol and progesterone concentrations lead to the following conclusions. First, the maintenance of the metrial gland is strictly progesterone-dependent. It is unlike the deciduoma which regresses spontaneously, even in the presence of progesterone. Secondly, the production of oestradiol receptor, but not of progesterone receptor, appears to be repressed in the metrial gland under the influence of progesterone. Thus, the tissue retains its ability to respond to progesterone because of a high concentration of progesterone receptor. It is difficult to attribute this high tissue progesterone receptor concentration to oestradiol stimulation since, even at low levels, oestradiol induces tissue regression. We suggest that the high progesterone receptor concentration could be due to constitutive (basal) progesterone receptor production.

Animals↗

Displacement of receptivity for nidation in the rat by the progesterone antagonist RU 486: a scanning electron microscopy study.

In the rat, the period of receptivity for nidation (implantation window) is characterized by specific change of the apical surface of the luminal uterine epithelium, such as the presence of large ectoplasmic projections (pinopodes). Under the conditions of this study, fully developed pinopodes appeared during normal pseudopregnancy on day 5 only. When RU 486 (5 mg/kg s.c.) was given once on day 1, the chronological limits of the appearance of these projections were changed. Fully formed pinopodes were observed on days 6-8 instead of day 5, indicating a displacement and enlargement of the receptive period. This property of the progesterone antagonist could be of clinical interest if it could be used to enlarge the 'implantation window' in women after replacement of in-vitro fertilized eggs.

Animals↗

Inhibition of egg development and implantation in rats after post-coital administration of the progesterone antagonist RU 486.

RU 486 was administered to rats on Day 1 or Days 1 + 2 of pregnancy. Endometrial sensitivity (i.e. decidualization in response to oil instillation) was delayed by 2.5 mg/kg injected s.c. on Day 1, and almost half of the animals also exhibited a delay in implantation of 1-2 days. Higher doses (5 or 10 mg/kg) administered on Days 1 + 2 reduced the number of implantations to zero in all animals. Apparently normal morulae were found up to the evening of Day 4 in the oviduct and/or the uterus of most animals. However, on the morning of Day 5, ova were detected in only 25% of the animals and all were in the uterus: none was at the blastocyst stage and they appeared to be degenerated or compacted morulae. Egg survival and rate of egg recovery from the uterus was not improved by early ovariectomy, showing that this antiprogestagen acts on these events independently of the presence of circulating oestrogens.

Abortifacient Agents↗

Scanning electron microscopy of postovulatory human endometrium in spontaneous cycles and cycles stimulated by hormone treatment.

The ultrastructure of the luminal surface epithelium was compared in endometrial samples taken from 23 normally cycling women and from 22 patients submitted to ovarian stimulation with clomiphene citrate (100 mg/day for 5 days), human menopausal gonadotrophin (hMG) and human chorionic gonadotrophin (hCG). On day 2 after ovulation, only four out of nine specimens taken from the women in the hormone-treated group were identical to those of normally cycling women. On day 6 after ovulation, only two out of the 13 biopsy specimens from the treated group were the same as those from normally cycling women at that stage. Apical protrusions (pinopodes), typical for this period of the cycle, were missing in 11 of the 13 endometrial samples from the treated group. These observations suggest that the hormonal treatment applied to induce ovulation (clomiphene citrate, hMG and hCG) can modify the normal development of the prenidatory endometrium, and may thus have a negative effect on the rate of egg implantation.

Adult↗

Influence of the embryo on the distribution of maternal immunoglobulins in the mouse uterus.

The effect of the embryo on the distribution of IgA, IgG and IgM was studied by an immunoperoxidase technique on mouse uterine sections, (1) during the first part of pregnancy and pseudopregnancy, and (2) in delayed implantation combined with different progesterone-oestradiol treatments designed to extend the delay or induce implantation, and in nonpregnant ovariectomized mice similarly treated. The number of glandular lumina containing IgA increased particularly from the implantation period, but in pseudopregnancy this number decreased from the morning of Day 4, and afterwards continued to decline. In delayed implantation, the number of glandular lumina containing IgA also rose considerably when implantation was induced by oestradiol, whereas under the same progesterone-oestradiol treatment, nonpregnant ovariectomized animals displayed no such increase. Significant staining for IgG in the stroma was observed on Day 4 of pregnancy and pseudopregnancy but prolonged staining for IgG was observed only during pregnancy. In addition, significant numbers of IgA-plasma cells in the stroma were observed mostly in uteri containing embryos. These results indicate that embryos might affect the process by which ovarian hormones regulate IgA and IgG distribution.

Animals↗

Failure to detect specific binding sites for prostaglandin F-2 alpha in membrane preparations from rat endometrium.

Membrane preparations from endometria of rats in different physiological states (e.g. pseudopregnancy, ovariectomized animals receiving progesterone + oestradiol or oestradiol alone) were studied for [3H]PGF-2 alpha binding by methods which detected PGF-2 alpha binding in ovary preparations and PGE binding in the same endometrial preparations. There was no evidence of high-affinity binding sites for [3H]PGF-2 alpha. Saturable [3H]PGF-2 alpha binding that increased with the onset of uterine sensitivity was detected but this binding does not fulfil all the criteria required for a PGF-2 alpha receptor and is probably due to binding to PG metabolizing enzymes in our preparations, or to binding of [3H]PGF-2 alpha to PGE binding sites. The failure to detect specific PGF-2 alpha binding sites seems to reflect a true absence of these sites in the rat endometrium.

Animals↗

Estrogen and progesterone receptors in the endometrium, myometrium, and metrial gland of the rat during the decidualization process.

Uterine cytosolic and nuclear receptors for estradiol (E2) and progesterone (P), were simultaneously determined in pseudopregnant rats subjected to a traumatic decidualizing stimulus (knife-scratch). The entire decidualizing endometrium, myometrium, and metrial gland were separated, homogenized, and studied on alternate days beginning with day 1 post trauma (pt) and extending to day 13 pt when even the metrial gland is regressing. The rise and fall in E2 and P receptors during the earlier stages of deciduoma differentiation confirmed the work of others. Splitting of the deciduoma on day 5 pt into antimesometrial and mesometrial segments showed a higher concentration of cytosolic P receptor in the well differentiated antimesometrial segment, whereas there was a higher concentration of E2 cytosolic receptor in the still differentiating mesometrial segment. The differences, measured as femtomoles per microgram DNA or per mg protein were statistically significant. The receptor changes in the myometrium were not as pronounced as in the endometrium especially with regard to the low myometrial levels of nuclear E2 and P. The metrial gland which comes into prominence while the deciduoma is regressing, showed sustained high concentrations of cytosolic P receptor. It is suggested that although initiated by the same decidualizing stimulus, the hormonal and receptor interplay in the metrial gland may be somewhat different from that of the deciduoma. The metrial gland merits further study because of an implied immunological role.

Animals↗

Endometrial prostaglandin E2 binding: characterization in rats sensitized for the decidual cell reaction and changes during pseudopregnancy.

As an initial step in testing the hypothesis that uterine receptivity for blastocyst implantation and sensitivity for decidualization are controlled in part by the presence of functional receptors for prostaglandin E2 (PGE2) in the endometrium, we have characterized the high-affinity binding of [3H]PGE2 to an endometrial membrane preparation from ovariectomized rats treated with progesterone and estradiol so that their uteri were sensitized for the decidual cell reaction. As determined by Scatchard analysis, a single class of [3H]PGE2 binding sites with an apparent Kd ranging from 2 to 6 nM and a capacity of approximately 100 fmol/mg protein was found. Prostaglandins E1 and E2 competed equally for binding while relative cross-reactivity of other prostanoids and compounds tested was less than 3%. Binding was temperature-dependent and reversible. Under the assay conditions used, no metabolism of [3H]PGE2 was detectable. Pretreatment of the membrane preparation with proteolytic enzymes, or by heating, reduced subsequent specific [3H]PGE2 binding. These data are consistent with the presence of endometrial PGE receptors in the sensitized endometrium. The binding of [3H]PGE2 to endometrial membrane preparations from rats on Days 2 to 7 pseudopregnancy was determined. No specific binding could be detected on Day 2. A low binding capacity was found on Days 3 and 4; this increased markedly on Day 5 and reached a maximum on Day 6. These data indicate that the onset of uterine receptivity/sensitivity is temporally correlated with the appearance of endometrial PGE binding sites.

Animals↗

Endometrial prostaglandin E2 binding during the estrous cycle and its hormonal control in ovariectomized rats.

Binding of [3H] prostaglandin E2 ([3H]PGE2) to endometrial membrane preparations obtained from rats at known stages of the estrous cycle and from ovariectomized rats treated with various combinations of progesterone and estradiol was determined. No specific, high-affinity binding of [3H]PGE2 could be detected by endometrial membrane preparations obtained throughout the estrous cycle. In ovariectomized rats treated with progesterone and estradiol to induce either the neutral, receptive or postreceptive phase of the endometrium for blastocyst implantation, the greatest concentration of endometrial PGE binding sites was found in the preparations from the neutral phase. Treatment of ovariectomized animals with estradiol and progesterone, alone or combined, revealed that endometrial PGE binding sites were progesterone-dependent, and were first detectable 48 h after the initiation of progesterone treatment. Following separation of the endometrial luminal epithelium and stroma in progesterone-treated ovariectomized rats, PGE binding sites were detected only in the stromal membrane preparation. The results indicate the endometrial PGE binding sites in the rat are under hormonal control and that no simple relationship exists between the concentration of endometrial binding sites and uterine sensitization for the decidual cell reaction.

Animals↗

Immunoglobulins in the mouse uterus during the oestrous cycle.

The distribution of IgA, IgG and IgM was studied by an immunoperoxidase technique on sections of mouse uteri at each stage of the oestrous cycle. Staining for IgG and IgA was highest at pro-oestrus, declined at oestrus and was very low during the other stages. At pro-oestrus IgG was found throughout the stroma, in the uterine lumen, and in 10% of glandular lumina; very few IgG-containing plasma cells were present. At pro-oestrus, IgA was found in the uterine lumen, and in most of the uterine glands, both in the lumen and in the epithelium; little IgA was present in the stroma. IgA-plasma cells were detected at each stage of the cycle and were particularly numerous at pro-oestrus and oestrus. These results suggest that IgA is secreted locally from plasma cells into the uterine gland through the glandular epithelium, but that IgG enters the stroma from the local capillaries. The obvious increase in IgG and IgA secretion at pro-oestrus, when plasma oestradiol levels are highest, supports the hypothesis that, during the oestrous cycle, the humoral immune response is regulated in the uterus by ovarian hormones.

Animals↗

Different responses of rat endometrial epithelium and stroma to induction of oestradiol binding sites by progesterone.

Rats were ovariectomized for 3 weeks and then treated for 3 days with 4 mg progesterone. The cytosolic oestradiol receptor content in the stroma cells was very high (approximately 21,000 binding sites/cell) as compared with that in the epithelial cells (approximately 3000 binding sites/cell). The nuclear receptor values were low (approximately 500 binding sites/cell) in both types of cell.

Animals↗

Estrogen receptors in the nidatory sites of the rat endometrium.

In ovariectomized rats treated with progesterone, implantation was induced by a minute dose of 17 beta-estradiol. Twenty-four hours later, the concentrations of estradiol receptor in nuclear and cytosol fractions prepared from the endometrium surrounding the blastocyst and the inter-implantation areas remained very low. This indicates that estrogen was not secreted by the blastocyst. The higher receptor content in cytosol from inter-implantation sites may reflect modifications accompanying the decidual reaction since our results show that there is no translocation of the receptor to the nuclei. The choice of the dye used to reveal the implantation sites is critical, since Trypan blue but not Evans blue binds steroids and thereby interferes with receptor measurements.

Animals↗

Oestrogen receptor in the baboon endometrium: cytosolic receptor, detection, characterization and variation of its concentration during the menstrual cycle.

A cytosolic oestrogen receptor from baboon endometria was detected and partially characterized. The apparent dissociation constant for oestradiol was 1.5 x 10(-10)--4 x 10(-10) mol/l. Steroids that competed with the [3H]oestradiol binding to the receptor were oestradiol and ethynyloestradiol greater than oestriol greater than 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.

Animals↗

Progesterone-induced oestrogen receptors in the rat uterus.

In ovariectomized rats progesterone acts like oestradiol at the endometrial, but not at the myometrial level, by increasing the number of oestrogen receptors in the cytoplasm. After 3 days of progesterone priming, the number of endometrial oestrogen receptors was found to be three times higher (P less than 0.05, Student's t-test) than control values. This progesterone-induced oestrogen receptor molecule appears identical in its physico-chemical properties (sedimentation coefficient, kinetic constants, steroid specificity) to that induced in the endometrium and myometrium under the influence of oestradiol. However, in the myometrium progesterone acts antagonistically reducing significantly (P less than 0.001, Student's t-test) the oestradiol-induced increase in the number of oestrogen receptors.

Animals↗