Glucocorticoid receptors in the spinal cord.
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Biomedical subjects
Publications and source records attributed to F Naftolin.
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Sexual differentiation of reproductive and behavior patterns is largely effected by hormones produced by the gonads. In many higher vertebrates, an integral part of this process is the induction of permanent and essentially irreversible sex differences in central nervous function, in response to gonadal hormones secreted early in development.
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There is an increasing frequency of early diagnosis of unruptured tubal ectopic pregnancy. This is due primarily to better diagnostic testing, such as the use of ultrasound and radioimmunoassay for the beta-subunit of human chorionic gonadotropin. The more stable conditions of the patients at the time of surgery caused us to reconsider the need for laparotomy in these cases. Therefore, an attempt was made to definitively treat 18 patients with ectopic pregnancy utilizing laparoscopic techniques. Eighteen patients had signs, symptoms, and diagnostic test results suggestive of unruptured ectopic pregnancy. Laparoscopy was employed to confirm the diagnosis. If the tubal swelling was less than 3 cm in diameter, a linear salpingostomy was carried out on the antimesenteric side of the fallopian tube, utilizing a cutting current. The contents were expressed and removed through a second puncture site. Vigorous lavage was used to cleanse the abdomen, and bleeding was controlled with electrocautery. All tubes which were operated upon were patent at the time of postoperative hysterosalpingography. Fifty per cent of those patients actively trying to conceive have achieved pregnancy. There were not repeat ectopic pregnancies or abortions. There were no immediate or long-term postoperative complications. This method represents an alternative to the treatment of unruptured tubal ectopic pregnancies in early gestation.
The association between the use of diethylstilbestrol (DES) and vaginal and cervical adenocarcinoma and adenosis in the progeny was first reported by Herbst et al. in 1971. This progeny will reach a peak as far as reproduction is concerned in this decade. It is estimated that 2 million women may be involved to varying degrees. Changes in uterine and cervical contour and structure have been detailed. Thus DES exposure and anatomic changes in the Müllerian system have been documented. In this report 16 women in the reproductive age group who were exposed to DES in utero and presented with infertility are discussed. On workup for infertility they were found to have unique tubal morphologic features consisting of a foreshortened, convoluted tube with "withered" fimbria with a pinpoint os at laparoscopy. The diagnosis could not be made at the time of hysterosalpingogram. Three patients had surgery in an attempt to correct this condition; and in all cases the surgery was unsuccessful. No statistical data is offered as to epidemiologic factors or incidence rates, but the suspected increase in infertility and ectopic pregnancy rates in patients with DES exposure may corroborate these findings.
The catechol oestrogen 2-hydroxyoestrone has been reported to lower serum prolactin concentrations acutely in normal women and it has been proposed that it may be effective in suppressing prolactin secretion in hyperprolactinaemic patients. Five women with hyperprolactinaemia and anovulation were studied. Following a control infusion, 2-hydroxyoestrone was given at a rate of 80 micrograms/h for 4 h. In no patient was there a fall in prolactin levels and no changes were observed in gonadotrophin concentrations. We conclude that a short-term infusion of 2-hydroxyoestrone, at a dose which will produce high blood levels of the steroid, does not affect prolactin or gonadotrophin secretion in hyperprolactinaemic states.
Sprague-Dawley rats were fed Purina Lab Chow with or without propylthiouracil (PTU), 0.001%, 0.01% or 0.1% PTU, ad libitum from weaning to vaginal opening. Mean values for all pubertal measurements are included in Tables 1 and 2. Growth rate (mean +/- S.E.) was significantly reduced (Neuman-Keuls test; P less than 0.05 level) in all PTU-fed rats (controls 4.9 +/- 0.1 g/day, 0.001% PTU 4.2 +/- 0.2 g/day, 0.01% PTU 3.4 +/- 0.2 g/day, 0.1% PTU 2.5 +/- 0.1 g/day), while age at vaginal opening in rats fed 0.001% PTU (35.8 +/- 0.6 days) or 0.01% PTU (36.1 +/- 0.9 days) was not significantly different from controls (36.0 +/- 0.6 days). Nevertheless, body weight at vaginal opening was lower in rats fed 0.1% PTU (87.6 +/- 4.7 g) than in controls (113.6 +/- 3.7 g). Pubertal body weight of rats fed 0.1% PTU was also reduced (88.6 +/- 3.7 g) but vaginal opening delayed (40.4 +/- 0.8 days). Proportions of body fat (6.1 - 5.1%), protein (15.0 - 14.1%), and water (72.4 - 71.3%) at vaginal opening were the same in control and PTU groups. Serum T4 was greatly diminished and similar in all 3 PTU groups, 0.2 - 0.3 microgram/100 ml, vs 4.8 +/- 0.2 microgram/100 ml in controls; in rats fed 0.1% and 0.01% PTU, T3 was 0.9 +/- 0.4 ng/100 ml and 0.9 +/- 0.6 ng/100 ml, respectively vs 72.6 +/- 5.6 ng/100 ml in controls, but not significantly reduced in the 0.001% PTU-fed group (60.7 +/- 7.9 ng/100 ml). In a second experiment, a group of weanling rats (pair-fed) was selected in which each member was fed the daily amount of control diet eaten by a corresponding age- and weight-matched 0.01% PTU-fed rat. During the experiment, both groups maintained the same body weight, growth rate, and food intake, however, only 45% (n = 11) of the pair-fed animals had vaginal opening by the time their 0.01% PTU-fed counterparts attained first estrus. Although one of the pair-fed (undernourished) rats attained first estrus, no eggs were found. Despite greatly reduced body weight (105.3 +/- 3.5 g vs controls 127.5 +/- 6.6 g), growth rate (3.5 +/- 0.2 g/day vs controls 5.5 +/- 0.1 g/day) and food intake (13.9 +/- 0.7 g/100g BWt/day vs controls 10.1 +/- 0.3 g/100g BWt/day), the 0.01% PTU-fed rats exhibited vaginal opening (36.9 +/- 0.8 days vs controls 35.6 +/- 1 days) and first estrus (39.6 +/- 0.9 days vs controls 36.4 +/- 1 days) at the usual age. In contrast, pair-fed rats had a lower % fat (4.5 +/- 0.1% vs PTU 6.8 +/- 0.4%) and higher % protein (16.5 +/- 0.3% vs PTU 14.3 +/- 0.3%) at the age when 0.01% PTU-fed rats attained first estrus. Serum prolactin levels at first estrus did not differ in rats fed control diet (26.5 +/- 12.4 ng/ml) or 0.01% PTU (8.8 +/- 1.9 ng/ml), or in pair-fed animals (8.8 +/- 4.5 ng/ml) at the age when PTU-fed rats reached first estrus.
The pharmacological effect of 2-hydroxyoestradiol (2-OHE2) and 4-OHE2 on concentrations of LH in the chronically castrated rat have been compared with that of oestradiol in order to determine whether the in-vivo activity is altered by insertion of a hydroxyl group at position 2 or 4 of the aromatic A ring; these derivatives are naturally occurring oestrogen metabolites. Four groups of six adult male rats were used 4 weeks after bilateral orchidectomy. The right jugular vein was exposed under ether anaesthesia and a basal blood sample taken (10.00 h) immediately before an intravenous injection of vehicle alone (0.1 ml ethanol with 0.01% ascorbic acid), oestradiol, 2-OHE2 or 4-OHE2 (10 micrograms of each in 0.1 ml vehicle). Blood was taken from each animal at 2, 4, 6, 8 and 24 h after treatment and serum assayed for LH. Baseline LH levels were similar in the four groups. At 2 h there was no change in 2-OHE2-treated rats but there was a significant decrease of serum levels of LH in rats treated with oestradiol and 4-OHE2 compared with vehicle-treated controls. The decrease in LH was quantitatively similar in oestradiol- and 4-OHE2-treated groups and was sustained at 4, 6 and 8 h, returning to control values at 24 h. In subsequent experiments the effects of lower doses of these two steroids were compared and the potency of 4-OHE2 was estimated to be about 25% that of oestradiol. In a further experiment, 2-OHE2 (100 micrograms) had no effect when given alone, but when injected i.v. immediately before treatment with 1 microgram oestradiol, it was able to inhibit the suppression of LH by oestradiol. In conclusion, 4-OHE2 had a potent effect in lowering plasma LH levels whereas 2-OHE2, even at a high dose (100 micrograms), did not suppress LH but it was able to inhibit the effect of oestradiol. These differences in biological activity may reflect more rapid metabolism of 2-OHE2 or differences in binding properties of these catechol oestrogens to the oestrogen receptor.
We have examined the effect of the catechol oestrogens 2-hydroxyoestradiol (2-OHE2), 4-hydroxyoestradiol (4-OHE2) and 2-hydroxyoestrone (2-OHE1) and their corresponding primary oestrogens on secretion of LH and FSH by enzymatically dispersed rat anterior pituitary cells in monolayer culture. Basal LH levels in the medium were significantly higher than in control wells when cells were exposed to 10(-8) M-oestradiol-17 beta for 40 h: oestrone and all three catechol oestrogens (in the same doses) also stimulated basal LH concentrations to levels quantitatively similar to those seem after oestradiol treatment. The same effects were observed when steroids were given at 10(-9) mol/l. Oestradiol, 2-OHE2, and 4-OHE2 but not 2-OHE1 increased pituitary responsiveness to LH releasing hormone (LH-RH) (given in a range of doses from 10(-11) to 10(-6) mol/l). The responses of cells treated with 2-OHE2 and 4-OHE2 were similar, though less than the response seen after treatment with oestradiol. This contrasts with the very different oestrogenic effects of 2- and 4-OHE2 previously observed in vivo. Neither oestradiol nor the catechol oestrogens had any effect on basal or LH-RH-stimulated FSH release.
The effects of acute surgical stress and the accompanying anesthesia on anterior pituitary function in female subjects was studied by means of frequent perioperative determinations of the circulating concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), growth hormone (GH), and thyroid-stimulating hormone (TSH). No appreciable alteration in the circulating concentrations of either LH or FSH could be detected. In contrast, the levels of PRL and GH were found to be markedly increased during the perioperative period, with the increase in pRL invariably preceding any noticeable alteration in GH levels. In addition, perioperative PRL but not GH levels were significantly higher (p < 0.01) in patients undergoing a major surgical procedure, in contrast to a minor one. Finally, this study furnishes detailed evidence of a small but significant (p < 0.05) increase in TSH levels in patients undergoing a major surgical procedure. These data indicate that augmentation of pituitary secretion of three stress-related hormones, but not gonadotropins, occurs during surgical procedures.
Immunohistochemical techniques were used to search for the presence of 17beta-estradiol dehydrogenase activity in human endometrial and placental tissues, with the use of antibodies raised against highly purified human placental 17beta-estradiol dehydrogenase. Sensitivity and specificity of the antibodies were documented by radioimmunoassay and immunodiffusion on cellulose acetate. Although staining was consistently demonstrated in the syncytiotrophoblast layer of term placentas, in both cytoplasm and nuclei, no immunohistochemical reaction was observed in endometrial samples. These results support the contention that placental 17beta-estradiol dehydrogenase is immunologically dissimilar from the endometrial enzyme.
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Five catechol estrogens and two 2-methoxyestrogens were compared for their relative affinity of binding to hypothalamic, pituitary, and uterine cytosol estrogen receptors; and for the kinetics of the catechols' methylation by hepatic catechol-0-methyltransferase. All of the catechol estrogens tested have similar Km's for 0-methylation (9-14 muM). Estrogen receptor affinities, however, differ widely. In hypothalamus, for example, where estradiol-17 beta has a Kd of 0.039 +/- 0.008 nanomolar, 4-hydroxyestradiol also binds tightly (0.12 +/- 0.02 nM), 2-hydroxyestradiol and 4-hydroxyestrone with intermediate affinity (0.26 +/- 0.06 and 0.28 +/- 0.07 nM, respectively), and 2-hydroxyestrone and 2-hydroxyestriol much less well (1.68 +/- 0.79 and 1.27 +/- 0.26 nM, respectively). The binding of the 2-methoxyestrogens is extremely weak. These receptor affinities roughly parallel the potencies of these compounds in altering gonadotropin secretion.
2-Hydroxyest radiol-17 alpha and 4-hydroxyestradiol-17 alpha, the catechol derivatives of estradiol-17 alpha, have reduced affinity for hypothalamic, pituitary, and uterine estrogen receptors, but retain a potency for interaction with catechol-0-methyltransferase equal to that of the natural, 17 beta-hydroxy catechols. This dissociation of receptor binding and catecholamine interactions may allow the use of the 17 alpha catechols as a probe for the mechanism of action of the catechol estrogens.
Serum prolactin and cortisol levels were measured in 24 patients entering the Royal Victoria Hospital infertility center both before and after a thorough physical examination that included a pelvic examination and a search for galactorrhea in both breasts. There was no significant change in the levels of prolactin or cortisol in the group as a whole in those with normal prolactin values and those with high basal prolactin values (P less than 0.05). The possible role of stress in the mediation of occasional elevation of basal prolactin values is discussed in relation to the serum cortisol levels.
The rising emphasis on conservative surgical treatment of the fallopian tube has generated a greater demand for methods of reparative surgery. Thus far, the use of surrogate tubes and allotransplantation of the fallopian tube hae not fulfilled the requirements for success. A case of homotransplantation of the human fallopian tube is presented. At surgery, a midsegment anastomosis was performed by grafting the good portion of the left tube to a viable segment of the right tube. The arteries and veins were then anastomosed with 9-0 silk and a single-layer closure; an operating microscope was used. Patency was documented with chromotubation, and bleeding was controlled with microcautery. Decadron and Phenergan were placed in the patient's abdomen along with 150 ml of saline. She was given systemic Decadron, Phenergan, and antibiotics pre- and postoperatively. Three months after surgery hysterography revealed a viable-appearing fallopian tube. The patient subsequently aborted an 8-week intrauterine gestation. Fallopian tube homotransplantation has a role in the treatment of infertility, but the patient population for which this procedure is applicable is limited.