Expression of the insulin-like and platelet-derived growth factor genes in human uterine tissues.

The human uterus repeatedly exhibits cyclic biochemical and cytological changes during the reproductive period of life. These changes are the result of a well-characterized endocrine network involving the hypothalamus, pituitary, and ovary. The exact nature of the mechanism(s) by which the sex steroids act on the uterus remains to be elucidated. Possible local mediators of hormonal action on the uterus include polypeptide growth factors. Using the method of RNA transfer blot hybridization, we have analyzed tissue samples from the cycling human endometrium and tissue samples of human myometrium and myometrial benign tumor (leiomyoma) for the presence of platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF) RNA. All the uterine tissues examined possessed RNA for PDGF-B chain and IGF-I and -II. Two transcripts were observed for PDGF-B chain, four were observed for IGF-I, and eight were observed for IGF-II. Overall, the relative abundance of PDGF-B chain RNA was consistent in all of the uterine tissues examined. In contrast, IGF RNA relative abundance varied. IGF-I RNA was highest in late proliferative stage endometrium, and IGF-II RNA was highest in early proliferative stage endometrium. Both IGF-I and IGF-II RNAs were greater in amount of leiomyoma than in myometrium. The increased IGF-I RNA in late proliferative-stage human endometrium correlates with the known elevation of estradiol secretion by the ovary and the increased concentration of uterine estradiol receptors during this stage of the menstrual cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of total progesterone receptor levels in various segments and tissues of the normal human uterus: the effect of short-term estrogen administration.

Total progesterone receptor levels (TRP) were measured in various tissues and segments of normal human uteri in basal conditions (late proliferative phase, control group, n = 6) and after short term estrogen administration (test group, n = 8). Similar trends of distribution were observed in both groups in basal endometrial TRP levels along the longitudinal axis, i.e. the highest levels were found at the height of the body and the lowest at the height of the internal os. Differences were found in the trends of distribution of the TRP levels between the two groups along the transverse axis of the uterus at the height of the fundus. In the control group TRP levels in the functional endometrium were higher than those in the basal endometrium and myometrium. In the test group, however, the trend was reversed. Since the RP is estradiol induced and dependent, these results indicate the possibility of a selective estrogen effect on various segments or tissues in the human uterus.

Progesterone challenge test in postmenopausal women with pathological endometrium.

Cytosolic and nuclear progesterone receptor levels (RPC, RPN) were measured in normal and in pathological human endometria after single-dose progesterone injection 1-3 h before tissue collection (test subjects) and the results compared to those obtained in controls (no progesterone treatment). In test cases of late proliferative or midcycle normal endometria and in estrogen-primed normal postmenopausal endometria, RPN levels were higher and RPC levels were lower compared with those obtained in control samples. In test cases of postmenopausal pathological endometria, histologically normal endometria of women with postmenopausal bleeding and in one case of endometrial polyp, RPN levels were also higher and RPC levels lower than those in the respective controls, but the change of distribution of the RP (cytosol/nuclear extract) was significantly lower than in normal endometrium.

Distribution of total estradiol receptor levels in various segments and tissues of the normal and pathological human uterus.

Estradiol receptor (RE2) levels were measured in normal (n = 22) and pathological (n = 14) human endometria and in various segments and tissues of the same uteri (n = 8). The highest total estradiol levels (TRE2) were found in midcycle normal cyclic endometria and the lowest in the secretory phase of normal cyclic endometria and in normal postmenopausal endometria (the TRE2 levels in the latter two groups were within similar ranges). The highest nuclear RE2 levels were found in proliferative-phase normal cyclic endometria. TRE2 levels in pathological postmenopausal endometria were high, in the range of those found in proliferative normal cyclic endometria, but the nuclear RE2 levels were low as compared with those in normal proliferative endometria. Examination of the distribution of the TRE2 levels in various segments and tissues of normal proliferative uteri revealed similar trends in all cases as follows: the highest levels were measured in the functional endometrium (fundus) and the lowest in the myometrium (fundus). Basal endometrial TRE2 levels decreased along the longitudinal axis from fundus to isthmus. In 4 cases, TRE2 levels in leiomyoma tissues were higher than those in the corresponding myometrium. These results indicate the possibility of a differing regulating mechanism of the RE2 in various segments or tissues of the human uterus.

Heterotopic pregnancy.

Three cases of heterotopic pregnancy, i.e. combined intra-uterine and extra-uterine pregnancy are reported. The complexities of diagnosis and management are presented.

Total estradiol and progesterone receptor levels and DNA concentrations in human endometrium with nonuniform postovulatory delay of maturation.

Total estradiol and progesterone receptor levels and DNA concentrations were measured in endometria of four women with nonuniform postovulatory delayed maturation of the epithelium. All four women underwent curettage on Days 21 to 23 of their cycle. The results in these women were compared with results obtained from a control group of women with histologically normal cyclic endometrium. In three women with corpus luteum defect, total estradiol and progesterone receptor levels and DNA concentrations were in the range of midcycle or early secretory normal (control) endometria. In one patient with a normally functioning corpus luteum, the above parameters were similar to those found in the late secretory phase of controls. Summation of the results of the present study along with those previously reported in endometria of women, both with uniform and nonuniform delayed maturation, indicate the possibility of endometrial postacceptorial progesterone defect, which may either be secondary to corpus luteum defect or a result of primary endometrial defect.

The diagnostic value of laparoscopy in women with chronic pelvic pain.

Laparoscopy was performed in 130 patients with chronic pelvic pain. Laparoscopy confirmed the preoperative diagnosis of pelvic inflammatory disease (PID) in 41 of 63 women with preoperative diagnosis of chronic PID (65%), whereas in 8 (13%), no pathologic findings were revealed. Laparoscopy directed the management in all 67 women who underwent the procedure to establish a diagnosis; in 16 (24%) of these, no pathologic findings were revealed. Of the total group, laparoscopy prevented laparotomy in 20 cases. These results are in accord with those of previous studies and emphasize the importance of laparoscopy in the management of women with chronic pelvic pain.

The effect of placenta previa localization upon maternal and fetal-neonatal outcome.

The present study evaluated the association between maternal and fetal-neonatal outcome in women with placenta previa (PP) and the site of PP, i.e. low lying, marginal, partial or total. The study group was composed of 154 women (159 newborns) and the control group of 300 woman (305 newborns). Of the various parameters examined, the following 3 were associated with PP localization: advanced maternal age was associated with major types of PP, while focal accretion of the placenta and neonatal mortality in cases of vaginal delivery were associated with minor types of PP. No connection was found between antepartum, intrapartum or postpartum blood loss and any specific type of PP. A review of the literature and the results of the present study revealed that the use of the modern aggressive (conservative-active) management protocol in women with PP has resulted in a significant reduction in the maternal and perinatal complication rates, as well as a relative decrease in the importance of major types of PP and a relative increase of that of the minor types.

Decreased induced retention of the progesterone receptor in the nuclear extract in human uterine leiomyoma in vivo.

Progesterone receptor (RP) levels were measured in the cytosol and in the 0.4 M KCl nuclear extract of human uterine leiomyoma, myometrium and endometrium; the synthetic progestin [3H]-R5020 was used as a ligand. The women were divided into groups A-D as follows: A, 7 women with no treatment; B, 7 women who received progesterone injection 1-3 h before tissue collection; C, 4 women who received conjugated estrogens 7-11 days before tissue collection; D, 5 women who received both conjugated estrogen and progesterone treatments. The following results were demonstrated: Total RP levels in the leiomyoma were significantly higher than the corresponding levels in the myometrium of the same uterus; after estrogen treatment these differences diminished. Leiomyoma challenged with progesterone expressed significantly lower RP levels in their nuclei than did the corresponding endometrium and myometrium. These results indicate the possibility of a defect of RP dynamics in human uterine leiomyoma.

Progesterone (P) receptor dynamics in estrogen primed normal human cervix following P injection.

Progesterone (P) receptor levels were measured in the cytosol and in the 0.4 M KCl nuclear extract in human cervical tissues with [3H]-R5020 as a ligand and the results compared with those obtained in the myometrium and endometrium of the same uteri. Tissue samples were obtained from 28 women, grouped as follows: group A, 12 premenopausal controls; group B, 7 perimenopausal women who received estrogen 7 to 11 days before operation; and group C, 9 perimenopausal and postmenopausal women who received estrogen as in group B plus P injection 1 to 3 hours before operation. Estrogen administration resulted in a significant rise in total P receptor levels in the cervix, compared with the endometrium and myometrium. P injection after estrogen priming resulted in down-regulation of the P receptor in the cervix to undetectable levels, whereas in the endometrium and myometrium it resulted only in redistribution of the P receptor, with higher nuclear levels and lower cytosol levels. These results indicate the possibility of a different mechanism of regulation of the P receptor in the human cervix, compared with that in the endometrium and myometrium.

Tubal pregnancy--reappraisal of incidence.

A longitudinal study of tubal pregnancies diagnosed and treated from 1967 to 1980 revealed a biphasic incidence with a rise after 1975. This rise was in effect due to a 'jump' in the rate of early diagnosed unruptured tubal pregnancies. The study results suggest that with the use of modern diagnostic methods, we are now detecting early cases of tubal pregnancy some of which, had they not been diagnosed, might have self-terminated.

Characterization of the nuclear progesterone receptor in normal human endometrium after progesterone injection.

Nuclear progesterone receptors (RPN) were characterized in the 0.4 M KCl nuclear extract of the endometrium using [3H]R5020 as a ligand, in women in the proliferative phase of the cycle (n = 5), in the midcycle (n = 5), in the secretory phase (n = 4), and in premarin-treated women (n = 3), 1-3 h following progesterone injection. The receptor character of the binding was demonstrated by high specificity for progestin binding, high saturable affinity for R5020 and a sedimentation constant of about 3S in sucrose density gradient. The RPN characteristics were similar in all 4 groups and were also similar to those of the remaining cytosolic RP. Despite the fact that total RP levels differed in all 4 groups, the percentage of the receptor that was measured in the nuclear extract was similar in all groups and ranged from 52 to 61% of the total RP levels.

Characterization of the nuclear progesterone receptor in normal Premarin-primed post-menopausal endometrium.

Nuclear progesterone receptors (RPN) were characterised in a 0.4 M KCl nuclear extract of Premarin-primed normal post-menopausal human endometrium after progesterone injection using [3H]R5020 as a ligand. The receptor character of the binding was demonstrated by the following findings: the high specificity for progesterone binding; the high saturable affinity (dissociation constant approx. 2.5 nM) for R5020; the sedimentation coefficient at high salt concentration (approx. 3 S); and the change in distribution of the RP following progesterone administration. These results indicate that normal post-menopausal human endometrium retains the property of translocation (2-step model) or nuclear activation and retention (nuclear receptor model) of the RP if it is exposed to the appropriate oestrogenic and progestational hormonal milieu.

Effect of progesterone injection on progesterone receptor levels and distribution in untreated and short-term Premarin-primed pre-menopausal and post-menopausal endometrium.

Cytosolic and nuclear progesterone receptors (RPC, RPN) were measured in post-menopausal endometria, using [3H]R5020 as the radioligand, and the findings compared with those in pre-menopausal endometria. Total RP levels (RPC + RPN) in post-menopausal endometria were low, i.e. less than 2000 fmol/mg DNA. A 7-11 day course of Premarin (conjugated equine oestrogen) treatment in post-menopausal subjects resulted in RP levels in 11818 +/- 3008 fmol/mg DNA, which were higher than those in proliferative, mid-cycle and Premarin-primed pre-menopausal endometria. Progesterone injection 1-3 h before tissue collection resulted in a change in the distribution of the RP in both premenopausal and post-menopausal Premarin-primed endometria and pre-menopausal proliferative and mid-cycle endometria. Following the progesterone injection RPN levels increased to 57 +/- 9% of the total as compared with 23 +/- 8% in endometrial samples from women who received no progesterone.

Progesterone receptor levels and distribution in different phases of the menstrual cycle and in estrogen-primed postmenopausal endometrium.

Progesterone receptor levels were measured in the cytosol and in the 0.4 M KCl nuclear extract of normal cyclic endometria in 49 women, classified into four categories: proliferative, midcycle, secretory, and estrogen-primed (four to 11 days); [3H]R5020 was used as a ligand. The women in each category were further subdivided into test and control groups; the women in the test group received a progesterone injection one to three hours before tissue collection. Both the nuclear progesterone receptor levels and the portion of the progesterone receptor in the nuclear extract were significantly higher in the test than in the control groups; among the test groups in the four categories, however, these changes were significantly smaller in women in the secretory category than in the other three categories. These results indicate that the progesterone receptor activation-translocation dynamics in human endometrium are dependent upon the hormonal status of the woman.

Characterization of the nuclear progesterone receptor in human uterine leiomyoma.

Progesterone binding components were characterized and measured in the 0.4 M KCl nuclear extract of Premarin-primed human leiomyoma (LM) following progesterone injection (n = 5) using [3H]R5020 as the ligand. The receptor character of the binding was demonstrated by: high specificity for progesterone and R5020 binding, high saturable affinity (Kd approximately 2.5 nM) for R5020, sedimentation coefficient in high salt concentration (approximately 3 S), change of distribution of the receptor after progesterone administration, i.e. an increase in the nuclear and decrease in the cytosolic receptor levels. Similar results were demonstrated in the corresponding myometria and endometria. The characteristics of the nuclear progesterone receptor in all three tissues of the test group were similar to those of the cytosolic progesterone receptor in the test group and in the control group (no treatment before operation, n = 5). These results indicate that the nuclear progesterone receptor in human uterine LM shares similar characteristics to those of the myometrium and endometrium.

Characterization and assay of the nuclear and cytosolic progesterone (P) receptors in Premarin-primed human endometrium and myometrium after single-dose P administration.

Progesterone receptors (RP) were characterized and measured in the 0.4 M KCl nuclear extract and in the cytosol of 7 to 11 days Premarin (Premarin, Ayerst Laboratories, New York, NY) primed human endometrium and myometrium with [3H]R5020 as the ligand. The test group comprised 12 women who received progesterone injection 1 to 3 hours before tissue collection; the control group numbered 10 women. Receptor characteristics in both the endometrium and the myometrium, in the nuclear extract and cytosol in the test group and in the cytosol in the control group, were similar and were demonstrated by (1) high specificity, (2) sedimentation constant of 4.7 to 6.5S in the cytosols and 2.8 to 3.9S in the nuclear extract, (3) saturable affinity with Kd of 2.2 to 3.5 nM and 1.9 to 3.3 nM, respectively. Total RP levels (nuclear extract and cytosol) ranged from 1030 to 13,270 and 1280 to 17,300 fmol/mg DNA, respectively, in the endometria of women in the test and control groups. In 13 of 14 women myometrial total RP levels were higher than in the endometrium. There was a significant difference in the distribution of the RP between the test and the control groups: 50% and 48% of the receptor were measured in the nuclear extract in the endometrium and myometrium, respectively, in the test group, compared with 25% and 21% in the control group (P less than 0.001).

Case report of two primary tumors: mullerian adenosarcoma and endometrial adenocarcinoma.

A rare case of two concomitant primary uterine neoplasmas in a 64-year-old patient who had received conjugated estrogens for the 3 preceding years is presented. Müllerian adenosarcoma, heterologous type, with stromal components suggestive of rhabdomyosarcoma, and adenocarcinoma of endometrium, were localized in different sites of the endometrium with no intermingling between them (combination tumor). The diagnostic and therapeutic problems are discussed.

Decreased ratio of total progesterone to total estradiol receptor levels in endometria of women with adult dysfunctional uterine bleeding.

Total estradiol and progesterone receptor levels (TRE2, TRP) were measured in endometria of women with adult dysfunctional uterine bleeding (n = 2) and compared to those of controls. The women in both groups were comparable with respect to age, history, light and electron microscopic endometrial morphology and dating; plasma levels of LH, FSH, estradiol and progesterone were similar in both groups. A wide range of TRE2 and TRP levels was measured in both groups; however, the levels of the ratio of TRP/TRE2 for each case were significantly lower in 18 of the 22 women with adult dysfunctional uterine bleeding and were in the range of the controls in the remaining 4. Possible explanations for these findings are presented.