[Prevention: problems of iodide administration in women, pregnant women and nursing women].
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Biomedical subjects
Publications and source records attributed to H G Bohnet.
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OBJECTIVES: To compare a composite ultrasonometry variable, the stiffness index (SI), with its two component variables of speed of sound (SOS) and broadband ultrasound attenuation (BUA), in identifying post-menopausal women with low bone mineral density (BMD) and/or osteoporotic fracture. METHODS: A cross sectional sample of 1217 women (mean (S.D.) age 53.9 (9.7) years) was studied. Risk factors for osteoporosis were assessed by detailed questionnaire and women with diseases, or those taking treatments known to affect bone metabolism were excluded. Women were allocated to one of four groups: pre-menopausal women (n = 476), healthy post-menopausal women (n = 583), post-menopausal women with low BMD (n = 101), and post-menopausal women with osteoporotic fracture (n = 57). An Achilles ultrasonometer was used to perform quantitative ultrasonometry (QUS) at the os calcis. The SI. calculated mathematically from SOS and BUA, was computed. RESULTS: Analysis of receiver operating curves (ROC) between healthy post-menopausal women and post-menopausal women with low BMD but no fracture, showed that the area under the curve (AUC) for SI was significantly greater than that for BUA (P < 0.001) or SOS (P < 0.05). For healthy post-menopausal women compared to women with fracture, the area AUC for SI was significantly greater than that for BUA (P < 0.05) or SOS (P < 0.001). No significant difference was found for AUC between BUA and SOS. CONCLUSION: QUS variables discriminated women with low density or fracture from healthy postmenopausal controls. The SI was a significantly better indicator than BUA or SOS in this retrospective study.
OBJECTIVE: To compare two new transdermal, continuous, combined formulations and an oral regimen of hormone replacement therapy (HRT) with respect to endometrial hyperplasia, bleeding patterns, and climacteric symptoms in postmenopausal women. METHODS: This was a randomized, open, parallel-group trial during 1 year in 441 postmenopausal women who received either a 10-cm2 patch of 0.025 mg estradiol (E2) and 0.125 mg norethisterone acetate, a 20-cm2 patch of 0.05 mg E2 and 0.25 mg norethisterone acetate twice weekly, or tablets of 2 mg E2 and 1 mg norethisterone acetate once daily. The efficacy variables were frequency of endometrial hyperplasia after 1 year of treatment, number of bleeding and spotting days from the fourth to sixth treatment months, relief of climacteric symptoms, and tolerability. RESULTS: The frequency of endometrial hyperplasia was no more than 2% after 1 year of treatment in all groups. One case of simple hyperplasia was detected among the women treated with 10-cm2 patches and two among those treated with oral HRT. From the fourth to sixth treatment months, amenorrhea occurred in 73%, 47%, and 66% of the women in the 10-cm2, 20-cm2, and oral HRT groups, respectively. The 10-cm2 patches and oral treatment were associated with fewer bleeding days than were the 20-cm2 patches (P<.001). During the last 3 months of the treatment year, amenorrhea was found in 100 subjects (86%) for 10-cm2 patches, 61 (65%) for 20-cm2 patches, and in 85 (79%) for oral HRT. All treatments alleviated the climacteric symptoms to a comparable extent. CONCLUSION: In postmenopausal women, 10-cm2 patches relieved climacteric symptoms and prevented endometrial hyperplasia at least as effectively as oral HRT. Amenorrhea was induced early in a high percentage of women using 10-cm2 patches and oral HRT, and these therapies seemed to be convenient, effective, and safe for estrogen deficiency symptoms in postmenopausal women.
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OBJECTIVE: To investigate whether various types of ovarian stimulation induce differences in endometrial development at the midluteal phase in infertile women. DESIGN: Assessment of stromal and glandular compartments in endometrial biopsies using morphometric criteria. SETTING: Institute for Hormone and Fertility Research, Hamburg, Germany. PATIENTS: The study included 18 women after treatment with human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) (group I), 23 women after clomiphene citrate (CC)/hMG/hCG treatment (group II), and 12 women after CC stimulation (group III). INTERVENTIONS: Endometrial biopsies and blood samples were taken simultaneously in the early to midluteal phase. To assess the time of ovulation, hormone analysis and regular checks by ultrasonography were performed. MAIN OUTCOME MEASURES: Morphometric evaluation of glandular and stromal structures revealed an impaired endometrial development after various treatment protocols. CONCLUSION: Ovarian stimulation in infertile women results in most cases in an elevation of steroid levels; however, the occurrence of an inadequate endometrial development might have an unfavorable influence on the outcome of implantation. Therefore, these findings may be of importance to the choice of treatment for infertility.
The human myometrium, in addition to the decidualized endometrium of the late luteal phase and of pregnancy, has been proposed as a second source of uterine PRL, since immunoreactive PRL was found in supernatants from myometrial explant cultures. We demonstrate here that: 1) the human (h) PRL gene is expressed in the myometrium in vivo; 2) myometrial PRL is identical to pituitary hPRL; 3) the encoding transcript differs from pituitary hPRL messenger (m) RNA but is homologous to decidual and IM-9-P3 lymphoid hPRL mRNA; and 4) the expression of myometrial hPRL mRNA is inhibited by progestin. hPRL mRNA was detected in freshly isolated myometrium by Northern blot hybridization and was larger than the pituitary message. Sequence and primer extension analyses revealed that the transcript is identical to pituitary hPRL mRNA downstream of the pituitary cap site and carries an extension of the 5'-untranslated region homologous to that of decidual/IM-9-P3 lymphoid hPRL mRNA. This mRNA species results from alternative transcription initiation and comprises exon 1a of the hPRL gene, which is not transcribed in the pituitary. hPRL mRNA steady state levels and hPRL secretion increased dramatically when myometrial explants were maintained in long term culture. In addition to the 23,000 mol wt form, myometrial explants synthesized a glycosylated hPRL variant (G-hPRL) which was approximately 500 Daltons larger than pituitary G-hPRL but of similar size as lymphoid G-hPRL (26,500). Lactogenic activity of myometrial conditioned medium paralleled that of pituitary hPRL in the Nb2 lymphoma bioassay and was neutralized by the addition of monoclonal antibody to hPRL. hPRL secretion and hPRL mRNA abundance were not affected by estrogen but were markedly reduced by medroxy-progesterone acetate, which was maximally effective at a dose as low as 10(-10) M.
The IM-9-P cell line is a variant of the human B-lymphoblastoid cell line IM-9 which ectopically secretes prolactin (hPRL). The heterogeneous line IM-9-P and three sublines of clonal origin, two of them positive and one negative for PRL gene expression, were subjected to cytogenetic analysis and compared with the reference line IM-9 which showed a normal female diploid karyotype. G-banding revealed several rearrangements in the chromosomes. Nine altered chromosomes including one stable marker chromosome were common to all analysed karyotypes of IM-9-P cells and their clones. A second marker chromosome 'mar2' occurred only in the karyotypes of the hPRL producing clones, but not in the non-producing clone. None of the visible alterations involve chromosome 6 which carries the PRL gene in humans.
Endogenous-luteinizing hormone (LH) surges may complicate the management of in vitro fertilization cycles. To investigate the effects of LH surges after hormonal stimulation 53 IVF cycles were analyzed by assessing LH levels three times daily until egg collection. In 43% the LH rise started before the planned exogenous trigger for ovulation was given, in 11% the rise occurred simultaneously with and in 45% after the injection of human chorionic gonadotropin. Three main patterns of serum LH surges were identified: (A) low-LH tonus with straight increase to maximum; (B) low tonus with elevation before straight increase; (C) high tonus with large variations but no prominant peak. These patterns were not related to the follicular estradiol increase, luteal steroid concentrations or resulting pregnancy rates.
In an attempt to identify factors that may be responsible for reproductive failure, we compared endometrial biopsies taken from infertile patients during the luteal phase of spontaneous cycles (n = 18) with those taken after ovarian stimulation (n = 18). Morphometric analyses were performed and compared with peripheral estradiol (E2) and progesterone levels at the time of supposed implantation. In stimulated cycles the number of glands per square millimeter was positively correlated to the E2 level. The morphometric data point to a measurable difference between the study groups, indicating an insufficient secretory transformation of the tissue in infertile women when compared with a group of fertile women. The observations suggest that hormonal stimulation occasionally results in impaired development of the endometrial glands.
The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulated prolactin (PRL) release from the PRL producing human B-lymphoblastoid cell line IM-9-P3 within 30 min with an EC50 of 5 x 10(-9) M. Increased release was entirely attributable to a loss from intracellular PRL pools. No change in hPRL mRNA was observed during 8 h of exposure to TPA. Prolonged exposure of the cells to 2 x 10(-7) M TPA, however, led to a maximal reduction of hPRL mRNA levels after 24 h and a subsequent recovery by 72 h. Secretory rates followed a corresponding kinetic. The relative abundance of c-myc mRNA was not affected, although a persistent inhibition of cellular proliferation occurred upon chronic exposure to TPA. The addition of dibutyryl cAMP caused a minor transient increase in hPRL secretion by 35% after 1 h.
The expression of the human prolactin (hPRL) gene is normally restricted to the anterior pituitary and the decidualized endometrium of the uterus. The human B-lymphoblastoid cell line IM-9-P3 ectopically expresses a PRL mRNA which is about 150 nucleotides larger than its pituitary counterpart even though the mature protein products appear identical. In the present study we show that human decidual and IM-9-P3 PRL mRNAs are similar in size, both being elongated relative to the pituitary transcript. The size difference persisted after removal of the 3' end poly(A) tract, whereas the PRL precursors synthesized in a cell-free translation system using mRNAs from the three tissues showed identical apparent molecular weights upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The elongation could therefore not be attributed to differences in the protein coding region or in the degree of polyadenylation and is suggested to reside in the 5' untranslated region of the molecule.
IVF techniques have recently attracted interest as a possible treatment of male subfertility. In order to clarify if semen profiles of men fathering a child after IVF differ significantly from those patients initiating a pregnancy after timed intercourse or AIH, we retrospectively compared sperm parameters in 67 males whose female partners were treated by IVF with those of 102 couples treated conservatively. In all male partners stimulation tests for FSH and LH, TSH and prolactin (PRL) had been performed as well as measurement of testosterone (T) levels. No significant differences were revealed for mean values of any of the classical semen parameters: volume, concentration, vitality, motility, normal morphology and results of the hypoosmotic swelling test between groups for men initiating a conception. Endocrine evaluation of the male patients detected no major hormonal imbalances associated with specific subnormal sperm parameters although regression analyses demonstrated relationships between semen volume and TSH as well as T, and between sperm concentration and PRL as well as FSH levels. We conclude that IVF techniques are not superior to cycle optimization with timed insemination in the treatment of andrological subfertility.
We examined whether the ectopic production of human(h) PRL by the human B-lymphoblastoid cell line IM-9-P3 is under hormonal control. We demonstrate that PRL secretion in this cell line is regulated by dexamethasone but not by other hormones known to modulate PRL secretion in the pituitary or decidua. Dexamethasone caused a reduction of secretion rates to 30% of control values after 3 day paralleled by a decrease in hPRL mRNA levels, without affecting cell viability. Half-life determinations of hPRL mRNA in control and dexamethasone-treated cells revealed a reduction of t1/2 from 16 to 4 h. PRL secreted by IM-9-P3 cells did not control its own secretion in an autocrine loop, nor did it serve as an autocrine growth factor.
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A variety of cell lines were examined by Northern blot hybridization for the expression of PRL or PRL-related mRNAs. We found that a human B-lymphoblast cell line transcribed a mRNA which hybridized to human PRL cDNA under high stringency conditions. The human lymphoblast cell line of interest is a variant subline of the IM-9 line that we have designated IM-9-P. The lymphoblast-derived PRL mRNA is approximately 150 bases longer than that produced by the human pituitary as determined by Northern blot analysis. IM-9-P PRL was immunoaffinity purified from conditioned medium and found to be identical in mol wt by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to human pituitary PRL. Moreover, IM-9-P PRL is biologically active in the rat Nb2 lymphoma mitogenic assay. Ribonuclease-H digestion of mRNA poly(A) tracts indicated that the size difference between pituitary and IM-9-P PRL transcripts was not due to an elongated poly(A) tail on the lymphoid PRL mRNA. Genomic Southern blot analysis showed no major rearrangements of the PRL gene in IM-9-P cells compared to the parent IM-9 line and human placenta DNA. Thus, it is highly likely that an elongation of the 5' and/or 3' untranslated regions of IM-9-P PRL mRNA account for the size difference with pituitary PRL mRNA. The PRL-producing IM-9-P line was cloned by limiting dilution, and a high PRL-producing clone IM-9-P3 and a non-PRL producer IM-9-P6 were isolated for further analysis. IM-9-P3 cells were found to secrete 40-50 ng PRL/10(6) cells.24 h regardless of cell density. The level of PRL mRNA also remained constant during exponential growth of IM-9-P3 cells. The existence of the PRL-producing IM-9-P3 clone and the IM-9-P6 clone which does not produce PRL as well as the IM-9 progenitor line provides a unique system with which to analyze the molecular mechanism of ectopic human PRL expression.
To elucidate different mechanisms by which bromocriptine, lisuride, and metergoline may inhibit prolactin (PRL) secretion and lactation in puerperal women, the PRL secretion patterns were examined by means of a stimulation test using an intravenous bolus of metoclopramide. After seven and 14 days of treatment, no significant difference in basal serum PRL levels was observed. However, women subjected to metergoline treatment had significantly higher responses of PRL to metoclopramide as compared with those treated with either bromocriptine or lisuride. Thus, the PRL-lowering mechanism of metergoline appears to be different from those of bromocriptine and lisuride.
Serum concentrations of 10 hormones in 162 hirsute women were examined. Mean testosterone, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) concentrations in these patients were 0.7 ng/ml, 10.0 ng/ml and 3.3 micrograms/ml, respectively; testosterone was elevated in 60.4% of the patients, DHEA was in 52.2% and DHEA-S was in 53.2%. Significant correlations were revealed among all these androgens. In the women who had normal testosterone levels DHEA was elevated in 50.0% and DHEA-S was in 22.2%. Cortisol levels did not show any significant correlation with the androgens examined in this study. Progesterone had a negative correlation with testosterone. Elevations of basal luteinizing hormone (LH) (greater than 20 mIU/ml) were seen in 21.7% of the patients. Stimulation tests using 25 micrograms luteinizing hormone-releasing hormone (LHRH) revealed enormous increase of LH (greater than 100 mIU/ml) in 18.7% of the women. Serum prolactin (PRL) was elevated in 38.3% of the patients; a bolus injection of metoclopramide (MCP) induced hypersecretion of PRL (greater than 160 ng/ml) in 48.0% of the women. These results indicate that the estimations of basal and LHRH- or MCP-induced hormone concentrations in hirsute women give useful clinical information for the understanding of their pathogenesis. More attention should be paid to basal hormone levels before suppression or stimulation tests of adrenal glands and ovary are performed.
During a pregnancy of a 35 year old woman, we could not detect HPL in the peripheral serum, whereas other hormones showed normal values. Fetal growth ceased in the 36th week and a live neonate was delivered by caesarean section. The histological findings of the placenta and the perinatal record were not so unusual that they could account for the absence of HPL. This case illustrates that fetal growth is possible without HPL-production.