External dose measurements to investigate the body-size dependence of personal dosemeter responses in areas affected by the Fukushima Daiichi nuclear accident.

To formulate necessary protective measures after a large-scale nuclear accident, it is crucial to understand the levels of radiation to which persons living in radionuclide-contaminated areas are exposed. Individual monitoring using personal dosemeters (PDs) plays a role in this, although PDs were not originally intended to be used by members of the public. The present study investigated PD responses in areas highly affected by the Fukushima Daiichi nuclear accident, as well as the dependence of those measurements on body size. Three types of commercially available electronic PDs, including D-shuttle, which has often been used in Fukushima, were placed on the front surfaces of three age-specific anthropometric phantoms imitating a 5-y-old, a 10-y-old and an adult male, and these phantoms were then exposed to radiation in an open field in the affected area. In the case of D-shuttle, the ratios of PD readings to the ambient dose rate for the 5-y-old phantom and the adult male phantom were 0.79 and 0.72, respectively. The ratios were somewhat higher for the other PDs; any PDs showed higher readings than the effective doses estimated by simulations based on the assumed ground deposition of 134Cs and/or 137Cs over the affected areas.

Distribution of natural radionuclides in NORM samples from North Abu Rusheid area, Egypt.

The North Abu Rusheid area in Egypt is a well-known high background natural radiation area (HBNRA) due to the existence of naturally occurring radioactive materials (NORMs) in mylonitic rocks. In this study, 27 rock samples were selected for dose estimation studies. 238U and 232Th were measured using inductively coupled plasma mass spectrometry (ICP-MS) and 40K was measured using sodium iodide (thallium) gamma-ray spectroscopy. The ranges of activity concentrations (Bq/kg) of 238U, 232Th and 40K in the samples varied from 270 ± 2 to 2120 ± 29, 350 ± 2 to 1840 ± 27 and 20 ± 2 to 1390 ± 35 with mean values of 980 ± 349, 770 ± 351, and 640 ± 402 Bq/kg, respectively. The radiological hazard parameters were estimated from activity concentrations of 238U, 232Th and 40K and compared to United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) values. The present study revealed that the hazard parameters were several times higher than the worldwide averages. The U/Th concentration ratio ranged from 0.7 to 3 and could be attributed to the presence of kasolite, uranothorite, zircon, and columbite in mylonitic rocks. From the radiological protection viewpoint, it is necessary to monitor natural radionuclides in these rocks prior to their use in residential and commercial construction materials.

Measurement of uranium isotope ratios in Fukushima-accident contaminated soil samples using multi collector inductively coupled plasma mass spectrometry.

In the present study, 137Cs and 238U activity concentrations, 234U/238U activity ratio, and 235U/238U isotope ratio were measured in fifteen soil samples collected from the exclusion zone around the Fukushima Daiichi Nuclear Power Station (FDNPS). The 137Cs activity concentrations of Fukushima-accident contaminated soil samples ranged from 29.9 to 4780 kBq kg-1 with a mean of 2007 kBq kg-1. On the other hand, the 238U activity concentrations of these soil samples ranged from 5.2 to 22.4 Bq kg-1 with a mean of 13.2 Bq kg-1. The activity ratios of 234U/238U ranged from 0.973 to 1.023. The 235U/238U isotope ratios of these exclusion zone soil samples varied from 0.007246 to 0.007260, and they were similar to the natural terrestrial ratio confirming the natural origin. Using isotope dilution technique, the 235U/137Cs activity ratio was theoretically estimated for highly 137Cs contaminated soil samples from Fukushima exclusion zone ranged from 5.01 × 10-8 - 6.16 × 10-7 with a mean value of 2.51 × 10-7.

Sorption-desorption coefficients of uranium in contaminated soils collected around Fukushima Daiichi Nuclear Power Station.

Various radionuclides including fission products and heavy nuclides were released into the environment during the Fukushima Daiichi Nuclear Power Station (FDNPS) accident. The dissolution followed by migration of deposited radionuclides of Cs, Sr and U on soils could take place to the local environment. Therefore, it is necessary to determine sorption-desorption coefficients of U in soil-water system around the FDNPS from a migration viewpoint. The determination of sorption coefficient Kd(S) as well as desorption coefficient Kd(D) for U has been carried out in the present study using a laboratory batch method. Stable U was used for sorption from simulated ground water onto contaminated soil samples collected from Okuma Town, Fukushima. Different soil parameters were measured to understand their effects on sorption and desorption processes. The obtained Kd(S) and Kd(D) values of U were compared with values of Kd(S) and Kd(D) of Cs and Sr and Kd(S)-U in known Fukushima accident contaminated soils reported in the literature for better understanding. It was observed that Kd(S)-U varied from 160 to 5100 L/kg, whereas Kd(D)-U ranged from 200 to 11000 L/kg. Kd(D) was higher than Kd(S) for U in these soils implying irreversibility of the sorption process. Pearson's correlation of Kd(S) values suggested that U sorption is affected by various soil parameters. However, desorption is decided by the nature of U species formed in sorption process and soil parameters like pH, presence of carbonates, Ca ions, clay minerals etc. to some extent. The comparison between Kd(S) and Kd(D) values for Cs, Sr and U revealed that unsorbed Sr could migrate farther than unsorbed Cs or U under the present experimental conditions. Both sorption and desorption studies are of great importance to understand migration of metal ions from contaminated sites to local uncontaminated areas.

Concentration ratios of stable elements for selected biota in Japanese estuarine areas.

For the estimation of radiation doses to organisms, concentration ratios (C ( R )s) of radionuclides are required. In the present study, C(R)s of various elements were obtained as analogues of radionuclides for algae, molluscs, and crustaceans, in eight estuarine areas around Japan. The elements measured were Na, Mg, K, Ca, V, Mn, Fe, Co, Ni, Cu, Rb, Sr, Y, Mo, Cd, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Pb, and U. The geometric mean (GM) values of C(R)s (GM-C(R)s) for alkali and alkaline earth elements, Mo, and U for all biota, as well as V for crustaceans, were less than 100 L/kg, while GM-C(R)s for the other elements were higher. When the obtained GM-C(R)s were compared with the C(R)s recommended in IAEA Technical Report Series 422 for marine organisms, no big differences between them were found; however, several elements (i.e. Cd and U for algae, Mn for molluscs, and Pb for crustaceans) were lower than the recommended C(R)s. In the present study, conversion factors (the ratio of C(R) for the whole body to that for muscle) for molluscs and crustaceans were also calculated, since data on edible parts of these organisms are generally available in the literature. For crustaceans, GM conversion factors of all the elements were more than one. For molluscs, GM conversion factors of rare earth elements and U were slightly higher than those for crustaceans, while GM conversion factors of the other elements were almost the same and less than 10. These results indicate that some elements tend to be concentrated in the internal organs of biota collected in the estuarine areas. For environmental radiological assessment, conversion factors from tissue to whole-body C(R) values are useful parameters.

URANIUM, THORIUM AND RARE EARTH ELEMENTS DISTRIBUTION IN FUKUSHIMA SOIL SAMPLES.

Uranium, thorium and rare earth elements (REEs) in soil samples contaminated by Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident was determined using inductively coupled plasma-mass spectrometry (ICP-MS). This information provides knowledge about concentration levels of REEs in soil samples as a background data after FDNPP accident. Chondrite-normalised REEs pattern does not show enrichment in concentrations of REEs, which could be related to FDNPP accident. The high concentration of these elements at few sampling points may be due to soil formation process from granitic rocks.

Expression of Tn and sialyl-Tn antigens in the neoplastic transformation of uterine cervical epithelial cells.

The expression of simple mucin-type carbohydrate antigens, Tn and sialyl-Tn antigens, was evaluated by immunohistochemical staining with monoclonal antibodies in normal squamous epithelium, dysplasia, carcinoma in situ, and invasive squamous cell carcinoma of the uterine cervix. The expression of the Tn antigen detected by HB-Tn1 and B1.1 was found in 17 (20%) and 19 (23%) of the 83 invasive carcinomas, respectively, but was not found in the 36 normal squamous epithelia, 22 severe dysplasias, or 24 carcinomas in situ. The sialyl-Tn antigen was detected by HB-STn1 and TKH-2 in 14 (64%) and 11 (50%) of the 22 severe dysplasias, 13 (54%) and 10 (42%) of the 24 carcinomas in situ and 48 (58%) and 42 (51%) of the 83 invasive carcinomas, respectively, but was completely absent in 36 normal squamous epithelia. Coexpression of the sialyl-Tn antigen was observed in 89% of the cases expressing the Tn antigen. No significant difference was observed between the immunoreactivities of the antigens in the metastatic lymph nodes and primary tumors. No correlation was found between the expression of each antigen and clinical state, histologic type, depth of invasion, parametrial spread, lymphatic and vessel permeation, lymph node metastasis, or 5-year survival rate. The expression of Tn and sialyl-Tn demonstrates a specific change in the neoplastic progression from carcinoma in situ to invasive carcinoma and from normal to dysplasia, respectively, in squamous cell neoplastic lesions of the cervix. Tn and sialyl-Tn antigens may be useful markers for biologic investigation of neoplastic transformation in cervical squamous cell carcinoma.

Characterization of a unique nuclear estrogen-binding component in an estrogen-responsive mouse Leydig cell tumor.

An estrogen-responsive mouse Leydig cell tumor line (Tumor 124958) has been shown to contain only a low-affinity binder for estradiol in the cytosol fraction. This differed from the putative estrogen receptor in terms of its hormone-binding specificity as well as affinity. In addition, the possibility that an estrogen receptor-like molecule exists in the nuclei even without hormonal stimuli was examined using purified nuclei. Scatchard plot analyses showed that these nuclei possessed a large amount of estrogen binder having a high affinity for estradiol and diethylstilbestrol. The content of this nuclear binding component was not diminished by using molybdate, a potent inhibitor for receptor activation, and in vitro incubation of collagenase-dispersed cells with estradiol did not cause significant increase in the number of nuclear binding sites when compared with the values obtained by direct incubation of isolated nuclei with estradiol. These results support the view that this nuclear estrogen binder is not due to artificial migration of the cytosol receptor into nuclei during homogenization. The characterization of this nuclear binding component under cell-free conditions revealed that its affinity for estradiol in Mg2+-containing buffer was temperature dependent (Kd 3 nM at 30 degrees and 12 nM at 0 degrees) without significant alteration in the number of maximum binding sites. Introduction of a chelating agent (ethylenediaminetetraacetate) into the buffer system abolished the temperature effect on the affinity, resulting in high affinity for estradiol at both low and high temperatures. These Mg2+ and temperature effects were reversible. In addition, when compared with putative nuclear estrogen receptors, this nuclear binding was observed to be relatively resistant to high salt or micrococcal nuclease treatments in relation to solubilization from nuclei. However, trypsin digestion was found to result in a marked decrease in the nuclear binding sites, indicating that this unique nuclear binding component contains a protein unit(s). These results suggest the possibility that this tumor line contains a unique unoccupied nuclear estrogen binder which might be able to transmit estrogen signals to tumor cell nuclei with regard to tumor growth.

Functional and morphological characteristics of transplantable rat pituitary tumors established in nude mice.

Two strains of transplantable rat pituitary tumors, MtT SA5 and MtT SA6, have been established in female nude mice from a single original pituitary tumor which had spontaneously occurred in a female Wistar rat at 759 days of age. MtT SA5 tumor produces prolactin (PRL), growth hormone, and adrenocorticotropic hormone, and MtT SA6 tumor secretes PRL and growth hormone. Additionally, both tumors induce severe nephropathy and promote pathogenicity of murine hepatitis virus, resulting in hepatic necrosis. Electron micrographs of MtT SA5 and MtT SA6 tumors revealed three and two types of cells, respectively, in reference to secretory granules. The tumors seem to consist of mixed population, each cell secreting each hormone. Since marked adrenal enlargement and relatively low serum corticosterone levels were found in MtT SA5-bearing rats, it is suggested that MtT SA5 tumor secretes adrenocorticotropic hormone and/or its related peptides which induce adrenal hyperplasia with little or no stimulation of corticoid production. In nude mice bearing MtT SA5 tumor, concentrations of growth hormone in serum and tumor tissue were exceedingly higher than those of PRL, while they were in the same magnitude in MtT SA6-bearing nude mice. We also found that PRL levels in serum and tumor tissue of MtT SA5-bearing nude mice were much higher in males than females, although those of MtT SA5-bearing rats were not significantly different in both sexes.

Growth inhibition by progestins in a human endometrial cancer cell line with estrogen-independent progesterone receptors.

The presence of estrogen-independent progesterone receptors (PgR) was demonstrated in a subline of a human endometrial cancer cell line, Ishikawa cells, although the original Ishikawa cells contained estrogen-inducible PgR. Scatchard plot analysis of cytoplasmic binding data in our subline (IK-90) revealed a high affinity binding site for R5020 (Kd, 1.0 nM) with maximum binding sites of 158 fmol/mg protein. Competition experiments showed a binding specificity similar to that of typical PgR. By low-salt sucrose gradient centrifugation, radioactive 8S and 4S peaks were found. The addition of 1 microM progesterone in culture medium resulted in a rapid nuclear translocation of cytoplasmic PgR. In contrast to the original cells, estrogen receptors could not be detected in IK-90 cells, and an addition of 17 beta-estradiol (10 nM) to culture medium failed to increase PgR. Accumulation of glycogen in cytoplasm of IK-90 cells in response to R5020 (0.1-1 microM) was observed by periodic acid-Schiff staining. The addition of R5020 to culture medium (0.1-1 microM) also caused a marked decrease in the growth of IK-90 cells, whereas the other steroids including 17 beta-estradiol, tamoxifen, testosterone, and cortisol had no significant effects. These results demonstrate for the first time the presence of a progestin-responsive human endometrial cancer cell line that contains estrogen-independent functional PgR. IK-90 cells appear to be an ideal model for studying the mechanism of the antiproliferative effect of progestin on endometrial cancer cells.

beta-Microseminoprotein/prostatic secretory protein is a member of immunoglobulin binding factor family.

Human seminal plasma contains a factor that binds human IgG, designated as immunoglobulin binding factor (IgBF). Under reducing condition IgBF interacts with anti-Leu-11b, a murine monoclonal antibody raised against human FcgammaRIII/CD16. IgBF shows no binding activity under non-reducing condition. Three components having IgBF activity were separated by HPLC and their amino acid sequences determined. The main IgBF showed structural identity to beta-microseminoprotein (beta-MSP), prostatic secretory protein of 94 amino acids (PSP94) and beta-inhibin. The slight variation in the reported sequences of these proteins has been attributed to analytical error. In the present study the molecular masses of main IgBF and beta-MSP/PSP94 were found to be identical by mass spectrometry. In addition, a large component of IgBF and a shorter beta-MSP consisting of 93 amino acids were identified. The binding of beta-MSP for human IgG and anti-Leu-11b antibody is demonstrable only under reducing condition, determined by Western blot analysis. The present data clearly show that IgBF is a family composed of at least three isoforms. One of the members is beta-MSP/PSP94. This family should be designated as IgBF.

Insertion/deletion polymorphism in the angiotensin-converting enzyme gene affects heart weight.

BACKGROUND: Angiotensin (Ang) II, a major regulatory factor for left ventricular mass, is generated from Ang I by ACE. ACE levels are associated with an insertion/deletion (I/D) polymorphism in the ACE gene. The ACE polymorphism should result in varied Ang II concentrations and hence affect left ventricular mass. We therefore investigated whether ACE genotype is a predictor of heart weight. METHODS AND RESULTS: From 693 consecutive patients autopsied between 1994 and 1998 in our hospital, patients with valvular disease, myocardial infarction, or cardiomyopathy were excluded. The remaining 443 autopsy patients were the subjects of our study. The heart weight at autopsy was corrected for body surface area. Genomic DNA was purified from the kidney, and ACE genotype was determined by polymerase chain reaction. Heart weight in the DD genotype (249. 9+/-49.9 g/m(2)) was significantly higher than that in the ID (230. 0+/-51.2 g/m(2); P<0.05) and II (226.8+/-49.8 g/m(2); P<0.01) genotypes. Heart weight was also positively related to age (r=0.145, P<0.0001) and coronary stenosis index (r=0.147, P=0.0019). Multiple regression analysis showed that a history of hypertension (P<0.0001), age (P=0.0001), and DD genotype (P=0.0154) were independent predictors of heart weight. CONCLUSIONS: ACE genotype predicts cardiac mass; however, it was less effective than epigenetic factors such as hypertension or age.

Formation of 5alpha-reduced C19-steroids from progesterone in vitro by a pathway through 5alpha-reduced C21-steroids in ovaries of late prepubertal rats.

Ovarian homogenates from 10-150-day-old rats were incubated with [3H]progesterone and NADPH. Also, ovarian homogenates from 28-day-old rats were incubated for 5-180 min with either [14C]progesterone, [3H]5alpha-pregnane-3,20-dione or [14C]progesterone plus [3H]5alpha-pregnane-3,20-dione. Following incubation, radioactive metabolites were isolated, identified, and measured by column and paper chromatography, with derivative formation and recrystallizations to constant specific activity. Prepubertal ovaries (10, 20, and 28 days of age) converted 15-60% of progesterone to C21-17-hydroxysteroids and C19-steroids. At 40 and 150 days of age (postpubertal), the formation of these steroids decreased to less than 2%. At 10 and 150 days of age, the major C19-steroids formed from progesterone were androstenedione and testosterone. At 20 and 28 days of age, however, no accumulation of these C19-delta4-3ketosteroids was found (less than 0.1% of each), at which time the conversion of progesterone to 5alpha-reduced C19-steriods, such as androsterone and 5alpha-androstane-3alpha,17beta-diol, reached 30%. In ovaries of 28-day-old rats, the results from incubation studies for the detection of metabolic pathways indicated two biosynthetic pathways leading to 5alpha-reduced C19-steroids, one from progesterone via 5alpha-reduced C21 steroids, such as 3alpha-hydroxy-5alpha-pregnan-20-one and 3alpha,17alpha-dihydroxy-5alpha-pregnan-20-one, and a second via 17-hydroxyprogesterone, androstenedione, and testosterone. It seems that the active 5alpha-reduction of C19-delta4-3-ketosteroids and the formation of 5alpha-reduced C19-steroids by the pathway through 5alpha-reduced C21-steroids, are present in the ovaries of older prepubertal rats and may be the biological significance.

Stimulatory effect of prolactin on luteinizing hormone-induced testicular 5 alpha-reductase activity in hypophysectomized adult rats.

Two pituitaries from 7-week-old female rats were grafted under the capsule of the left kidney of 50-day-old male rat to induce hyperprolactinemia. All of the pituitary-grafted and sham-operated rats were hypophysectomized at 56 days of age. The hypophysectomized rats in groups of 4 were given daily sc injections of saline or 9 micrograms NIADDK-ovine-(o)LH-23 for 4 and 5 days starting from days 58 and 70, respectively (short and long term hypophysectomized groups). The metabolism of [3H]progesterone or [14C]androstenedione by testicular homogenates, concentrations of testosterone and 5 alpha-androgens (androsterone plus 5 alpha-androstane-3 alpha, 17 beta-diol) in the serum and testes, and testicular LH receptors were estimated. Hypophysectomy caused significant decreases in testicular enzyme activities per gram of tissue, androgen production, and testicular LH receptors. In the testes of hypophysectomized rats, LH treatment significantly stimulated 5 alpha-reductase and 17-hydroxylase activities. Although pituitary grafts alone showed little or no effect on these testicular enzyme activities, hyperprolactinemia induced by the grafts markedly enhanced the LH-stimulated 5 alpha-reductase activity in both groups, especially in the long term hypophysectomized group. Therefore, androsterone and 5 alpha-androstane-3 alpha,17 beta-diol were shown to be the major C19-steroid products (immature type of testicular androgen production) in the LH- and PRL-stimulated testes of long term hypophysectomized adult rats. On the other hand, hyperprolactinemia was associated with a significant inhibition and a slight increase of the LH-stimulated 17-hydroxylase activities in the short and long term hypophysectomized groups, respectively. This difference can be attributed to both a PRL-induced increase in testicular LH receptors and a PRL-induced inhibition of 17-hydroxylase via a postreceptor mechanism(s). The present findings demonstrate for the first time that PRL directly stimulates LH-induced 5 alpha-reductase activity in the testes. It appears that PRL may play a role in the increased production of 5 alpha-C19-steroids and the parallel decrease of testosterone production in immature rat testes.

Retinoic acid enhances cell responses to epidermal growth factor in mouse mammary gland in culture.

Addition of epidermal growth factor (EGF) at up to 100 ng/ml to the medium of cultured explants of mouse mammary gland increased thymidine incorporation into DNA dose dependently. Addition of retinoic acid alone at 10 micrograms/ml to the medium had no significant effect on DNA synthesis, but addition of EGF with retinoic acid enhanced the EGF-stimulated DNA synthesis. Furthermore, pretreatment of mammary explants with retinoic acid enhanced the effect of EGF plus retinoic acid on cell growth. EGF inhibited the synthesis of casein and decreased alpha-lactalbumin activity of mammary explants in culture in the presence of insulin, cortisol, and PRL. Retinoic acid alone had no significant effect on the synthesis of casein, but suppressed alpha-lactalbumin activity dose dependently. Concomitant addition of retinoic acid with EGF had no significant effect on EGF-induced inhibition of casein synthesis, but enhanced EGF-induced inhibition of alpha-lactalbumin activity dose dependently. Measurement of specific binding of [125I]EGF to mouse mammary glands in culture demonstrated that pretreatment of the explants with retinoic acid slightly, but significantly, enhanced the specific binding of EGF to its cellular receptors.

Monoamine oxidase in rat ovary during the estrous cycle. A histochemical study by a new coupled peroxidatic oxidation method.

A new coupled peroxidatic oxidation method for histochemical detection of monoamine oxidase (MAO) was applied to rat ovary. With this new method, fixed tissues could be used, and two forms of MAO could be identified by use of selective inhibitors. MAO activity was observed in the corpora lutea, interstitial gland cells, and blood vessels. In the corpora lutea, no activity was detected during the first estrous cycle, but strong activity was observed in the next two cycles. MAO in blood vessels showed characteristic changes of activity during the estrous cycle. The results suggest that MAO activity might possibly be involved in ovulation and progesterone metabolism in the ovary. Like other organs, rat ovary was found to contain two types of MAO; type A MAO was predominant in the corpora lutea. On the other hand, only one type of MAO, type B, was found in the blood vessels.

Effect of calmodulin inhibitors on thyroid hormone secretion.

The effect of calmodulin inhibitors, N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) and trifluoperazine, on TSH-induced thyroid hormone secretion from rat thyroid was examined in vivo and in vitro. The ip administration of 5 mg W-7 to the rat inhibited T4 and T3 secretion from rat thyroids at 2, 3, and 4 h after the ip injection of 2 IU TSH, and so did the ip injection of trifluoperazine at 3 and 4 h. However, the ip injection of N-(6-aminohexyl)-1-naphthalene sulfonamide as a control substance did not show any significant inhibition of T4 and T3 release. To identify the site of action of calmodulin, the effect of W-7 on (Bu)2cAMP-induced thyroid hormone secretion was tested in vitro. One hundred micromolar W-7 completely inhibited T4 release from the rat thyroid when it was enhanced by TSH or (Bu)2cAMP, suggesting that the inhibitory effect of W-7 is subsequent to cAMP formation. These results suggest that calmodulin may play a role in thyroid hormone secretion from the thyroid, acting beyond cAMP formation.

Suppression of luteinizing hormone in castrated women by the administration of human chorionic gonadotropin.

The suppressive effect of human chorionic gonadotropin (hCG) on luteinizing hormone (LH) and/or LH-beta was studied by specific LH-beta radioimmunoassay following hCG administration. Eight castrated women were each administered 10,000 IU of hCG in a single intramuscular injection and five women in the control group were injected with saline. The serum level of hCG increased after the injection, reaching 217.6 mIU/ml after 8 h. There was a significant suppression of LH levels as compared to those of the control group and the pre-injection levels: 68.2% 1 h after injection, 64.7% after 2h, 65.5% after 4 h, 77.0% after 8 h, 78.6% after 12 h, and 78.2% after 24 h. There was no significant suppression of the follicle-stimulating hormone (FSH) as compared to the preinjection and control values. Serum concentration of estradiol1 was not detectable either before or after the hCG injection. We conclude that hCG has a suppressive effect on LH and/or LH-beta secretion not mediated by estradiol.

Clinical and endocrinological analyses of patients with galactorrhea and menstrual disorders due to sulpiride or metoclopramide.

The clinical courses of galactorrhea and menstrual disorders were studied in 18 women with galactorrhea induced by sulpiride (SLP) or metoclopramide (MCP) given for the treatment of gastrointestinal diseases. The response of PRL and TSH to 500 micrograms iv TRH and the response of LH and FSH to 100 micrograms LRH were assessed by retrospective analysis during treatment in nine patients (six, SLP; three, MCP) and shortly after the end of treatment in nine patients (seven, SLP; two, MCP). The average time from the initiation of treatment to the onset of galactorrhea was 27.2 +/- 4.7 (mean +/- SE) days in the 13 SLP-treated patients and 23.2 +/- 5.8 days in the 5 MCP-treated patients. Five of the SLP-treated patients experienced amenorrhea, four had oligomenorrhea, and one had dysfunctional bleeding. In the MCP-treated patients, oligomenorrhea and dysfunctional bleeding occurred in one each. The average length of time from the end of treatment to disappearance of galactorrhea was 50.0 +/- 7.3 days in the SLP-treated patients and 56.6 +/- 12.1 days in the MCP-treated patients. Cyclic uterine bleeding returned within 2 months after treatment was stopped. Elevated PRL levels with good response to TRH were observed in four of six patients during SLP treatment, and in two of three patients during MCP treatment. Basal PRL levels and response to TRH were normal in almost all patients after the drugs were withdrawn. Normal HL and FSH levels with exaggerated responses of LH to LRH were observed in most patients during treatment, whereas the response of LH to LRH was normal in about half of the patients after treatment. Our findings suggest that hyperprolactinemia in patients treated with SLP or MCP may be in part the cause of both galactorrhea and menstrual abnormalities, and that these symptoms can be reversed by stopping treatment, provided the patients have not taken the drugs for longer than a year.

Estrogen induces the release of luteinizing hormone-releasing hormone in normal cyclic women.

The plasma concentrations of immunoreactive LRH, LH, and FSH were determined by RIA every 6 h until 72 h after iv administration of conjugated estrogens during the midfollicular phase. The percentage change in LH from the preinjection level showed a biphasic pattern after the injection of conjugated estrogens, i.e. significant suppression (-70%) from 6-42 h after the injection, followed by a rebound increase with a peak (+150%) at 56 h. Plasma FSH after the injection also showed a biphasic pattern. The plasma immunoreactive LRH levels were unchanged until 32 h after the injection, but then increased significantly (P less than 0.02) to 160% of the preinjection level at 42 h and then decreased rapidly. These data indicate that 1) estrogen administration results in increases in plasma immunoreactive LRH and LH, and the peak of plasma LRH precedes that of gonadotropin; and 2) the negative feedback effect of estrogen on gonadotropin secretion may not be mediated through LRH.