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Biomedical subjects

W Rohde

Publications and source records attributed to W Rohde.

At least 109 records · Page 6Linked to original sources

The effect of an acute maternal stress on beta-endorphin and growth hormone releasing factor in the rat fetus.

Pregnant rats were injected with saline or L-tyrosine methylester HCl (200 mg/kg) and subjected to an acute forced immobilization stress on day 20 of gestation. At 10, 30, 60, and 120 minutes after the onset of stress, their fetuses were dissected out, and the contents of hypothalamic and pituitary immunoreactive beta-endorphin (IR-beta-EP) and hypothalamic immunoreactive growth hormone-releasing factor (IR-GRF) were determined by specific radioimmunoassays. The maternal stress arose a significant decrease of hypothalamic IR-beta-EP at 30 minutes, while pituitary IR-beta-EP slightly elevated at 30 minutes, then declined at 60 minutes. Hypothalamic IR-GRF showed a gradual increase during the maternal stress. Tyrosine supplementation tended to attenuate stress-induced changes in hypothalamic and pituitary IR-beta-EP, but the response of hypothalamic IR-GRF was less modified by tyrosine. These results showed the functional changes in fetal central beta-EP and GRF under maternal stress in the late gestational life, and suggested that catecholaminergic regulations participate, at least in part, in the fetal neuroendocrine response to maternal stress.

Animals↗

Effect of medial preoptic oestradiol implants on hypothalamic beta-endorphin concentration.

Twenty-four-day-old immature and cyclic female rats in metoestrus were ovariectomized and bilaterally implanted with oestradiol benzoate (OB) and cholesterol at a ratio of 1:360 or with cholesterol alone in the medial preoptic area (MPOA), or, for control, the hypothalamic dorsomedial nucleus. Estimation of beta-endorphin immunoreactivity in the ventromedial-arcuate-median eminence region at 6 and 3 days after implantation, respectively, revealed a significantly higher concentration in rats implanted with OB in the MPOA as compared to those implanted with cholesterol. OB implants placed in the dorsomedial nuclei were ineffective in this regard. The hypothesis is put forward that inhibition of hypothalamic beta-endorphin release as probably resulting from the implantation of OB in the MPOA may be related to desensitization of the negative oestrogen feedback that is induced by similar preoptic oestrogen implantation.

Animals↗

Teratogenetic maternofoetal transmission and prevention of diabetes susceptibility.

Gestational diabetes and impaired glucose tolerance in pregnancy were found to be important teratogenetic risk factors for the development of diabetes in the offspring. Mechanisms of action and prevention of maternofetal transmission of teratogenetic susceptibility to diabetes are presented. Gestational diabetes induced in the F0 generation produced the following effects in the F1 and/or F2 generation: Early postnatal hyperinsulinaemia, decreased noradrenaline and serotonin and increased endorphin concentrations in specific brain regions, permanent hypoplasia of the hypothalamic ventromedial nuclei, decreased insulin responsiveness to glucose, impaired glucose tolerance and increased diabetes susceptibility.

Animals↗

Sex-specific postnatal development of negative oestrogen feedback in rats.

Experiments were performed in immature and adult male and female rats to study the postnatal development of the negative oestrogen feedback in males and to investigate the mechanisms underlying this development. The following results were obtained: 1. Immature male and neonatally androgenized female rats were less responsive to the LH-inhibiting effect of oestradiol benzoate (OB) than untreated females. In contrast, long-term castrated adult males and females with the androgen-induced persistent oestrus syndrome were distinctively more sensitive than cyclic females to the negative feedback action of oestrogen. 2. The low oestrogen sensitivity in prepubertal males is probably caused by the testicular androgen secretion during the perinatal critical differentiation phase, because after neonatal castration, the LH response to OB injected at 21 days of age did not differ between both sexes. 3. As opposed to the peripubertal desensitization to the negative feedback action of testosterone, the sensitivity to the inhibitory effect of oestrogen on LH secretion did not decrease in males at the time of puberty. 4. Whereas former studies have shown that implantation of OB in the medial preoptic area results in significant reduction of the oestrogen sensitivity in female rats, medial preoptic implants containing oestradiol, testosterone or 5 alpha-dihydrotestosterone did not diminish the LH-suppressing effect of s.c. injected OB in males. The results suggest that 1. a marked sex difference exists in the postnatal development of the negative oestrogen feedback in rats. 2. Higher oestrogen sensitivity in adult male as compared to adult female rats may depend, at least partly, on prepubertal and cyclic desensitization of the negative oestrogen feedback in females and more or less constant sensitivity in males from infancy to adulthood. 3. In males the oestrogen sensitivity seems to be settled for long by the testicular androgen secretion during the perinatal critical differentiation phase. 4. The prepubertal increase of gonadotrophin secretion necessary for the induction of male puberty may mainly be caused by diminution of the gonadotrophin-inhibiting effect of androgens and by the decline of testicular release of inhibin. 5. The oestrogen-induced desensitization of the negative oestrogen feedback mediated by the medial preoptic area is probably a sex-specific mechanism that is only operative in female rats.

Aging↗

Diminished oestrogen sensitivity and increased ovulation rate in adult female rats after prepubertal treatment with oestrogen or pimozide.

Immature female rats were implanted with oestradiol benzoate or cholesterol in the medial preoptic area at different ages, and the inhibition of the ovariectomy-induced increase of LH secretion by s.c. injected oestradiol was investigated. Medial preoptic oestrogen implants reduced the inhibition of LH secretion in 4-week-old rats, but not in younger animals. Elevation of the circulating oestrogen concentration or suppression of the central nervous dopamine activity by daily injections of oestradiol and pimozide, respectively, from Day 26 to the day of vaginal opening, i.e. during the time when the mechanism of the oestrogen-induced desensitization of the negative oestrogen feedback matures, resulted in considerable diminution of the LH-inhibiting effect of oestradiol in ovariectomized adult females. In intact cyclic rats, both prepubertal treatments led to a significant increase of the average number of eggs per ovulation that was mainly caused by reduction of the number of animals with a low ovulation rate.

Animals↗

[Immunohistochemical detection of growth hormone-releasing factor (GRF) in neuroendocrine tumors].

We examined formalin-fixed, paraffin-embedded human tumors (42) from autopsies and surgical specimens for the presence of human pancreatic GRF-40 using the unlabeled antibody peroxidase-antiperoxidase method to assess the prevalence of tumors containing GRF, to define their primary sites and cellular derivations, and to correlate clinical and pathological features. Two paragangliomas, 1 pancreatic endocrine tumor, 1 bronchial carcinoid and 1 ganglioneuroma were immunoreactive for GRF. Of the GRF-containing tumors, only one bronchial carcinoid and one paraganglioma were associated with acromegaly.

Carcinoma, Adenoid Cystic↗

Somatomedin-C in active and successfully treated acromegaly.

Sm-C concentrations in serum were found significantly different in either active acromegaly or following successful treatment with pituitary adenomectomy. Although after normalization of serum GH the Sm-C levels sometimes exceeded the normal range no overlap was found between both groups. Exceptionally two acromegalic patients showed elevated Sm-C levels in spite of normal GH values. Likewise, a high Sm-C concentration was found in one patient suspective of ectopic GH secretion with only moderately elevated serum GH. Sm-C determinations are judged as a good adjunct to usual diagnostic methods which in special cases of acromegaly can be even superior to measurements of serum GH.

Acromegaly↗

Influence of transposable elements on the structure and function of the A1 gene of Zea mays.

The structure of the A1 gene of Zea mays was determined by sequencing cDNA and genomic clones. The gene is composed of four exons and three short introns. The 40.1-kd A1 protein is an NADPH-dependent reductase. Germinal derivatives of the mutable a1-m1 allele with either recessive or wild-type phenotype have been isolated. Sequence analysis of these revertant alleles indicates that frame-shift mutations abolish A1 gene function, whereas one additional amino acid within the protein sequence still allows wild-type gene expression. The presence of a second, promoter-like structure, upstream of the functional A1 gene promoter is discussed with respect to its possible involvement in differential expression of the A1 gene. The structure of the a1-m2 8004, 3456 and 4412 alleles, featuring distinguishable phenotypes in the presence of Spm(En), was also determined. In all alleles the 1080-bp-long inhibitor (I) element is located 15 bp upstream of the CAAT box of the A1 gene promoter. The unusual response of a1-m2 alleles to trans-active signals of the Spm(En) element is discussed with respect to the position of the I inserts. Also presented are data on the structure and insertion sites of transposable elements determined by cloning and sequencing of the mutable a1 alleles a1-mpapu, a1-mr 102 and a1-ml.

Alcohol Oxidoreductases↗

Sexual differentiation of gonadotrophin secretion, sexual orientation and gender role behavior.

The positive estrogen feedback was found to be a relatively sex-specific reaction of the hypothalamo-hypophyseal system in rats as well as in human beings. It is dependent--most of all--on the estrogen convertible androgen level during sexual brain differentiation, but also on an estrogen priming effect in adulthood. The lower the estrogen convertible androgen or primary estrogen level during brain differentiation, the higher is the evocability of a positive estrogen action on LH secretion in later life. In clinical studies, we were able to induce a positive estrogen feedback on LH secretion in most intact homosexual men in clear-cut contrast to intact hetero- or bisexual men. These findings were strongly confirmed by Gladue and associates. In addition, the evocability of a positive estrogen feedback was also demonstrable in most homosexual male-to-female transsexuals in significant contrast to hetero- or bisexual male-to-female transsexuals. These findings suggest that homosexual males possess, at least in part, a predominantly female-differentiated brain, which may be caused by a low estrogen convertible androgen level during brain organization. Recently, the following relations were found between sex hormone levels during brain differentiation and sex-specific responses in adulthood: (1) estrogens--which are mostly converted, however, from androgens--are responsible for the sex-specific organization of gonadotrophin secretion and hence the evocability of a positive estrogen feedback in later life; (2) estrogens and androgens, occurring during brain differentiation, predetermine synergistically sexual orientation and (3) androgens--without conversion to estrogens--are responsible for the sex-specific organization of gender role behaviour in later life. Furthermore, the organization periods for sex-specific gonadotrophin secretion, sexual orientation and gender role behaviour are not identical but overlapping. Thus, combinations as well as dissociations between deviations of the neuroendocrine organization of sex-specific gonadotrophin secretion, sexual orientation and gender role behaviour are conceivable. Most recently, female-type sexual orientation could be converted to male-type sexual orientation in adult rats by administration of the dopamine agonist and serotonin antagonist lisuride.

Androgens↗

Influence of the medial preoptic dopaminergic activity on the efficiency of the negative estrogen feedback in prepubertal and cyclic female rats.

Immature and adult female rats were bilaterally implanted in the medial preoptic area (MPOA) or hypothalamic ventromedial-arcuate region (VMAR) with the dopamine (DA) antagonist, pimozide, or the DA agonist, apomorphine, and the sensitivity to the LH-inhibiting effect of a subcutaneous injection of estradiol benzoate (EB), the onset of puberty and ovarian cyclicity were investigated. Diminution of the inhibitory effect of EB on LH secretion was recorded in ovariectomized immature and adult females implanted in the MPOA with pimozide. This response was not obtained in rats implanted in the VMAR. In contrast, medial preoptic, but not intrahypothalamic, implantation of agar pellets containing apomorphine resulted in enhanced sensitivity to estrogen both prepubertally and during the ovarian cycle. The sensitizing effect of apomorphine was completely prevented in prepubertal rats by pretreatment with EB for 6 days. Bilateral implantation of pimozide-agar pellets in the MPOA of 28-day-old intact females induced significant advancement of the onset of puberty, whereas sexual maturation was not affected by daily subcutaneous injections of the DA antagonist from day 28 till the day of vaginal opening. In adult 4-day-cyclic rats fitted with guide cannulae, the forthcoming ovulation was delayed for about 7 days as compared to the controls implanted with agar if apomorphine was placed in the MPOA from the morning of metestrus to the morning of diestrus. Similar implants located in the VMAR were ineffective in this regard. The results suggest that: (1) low DA activity in the MPOA reduces and high activity enhances the sensitivity of the negative estrogen feedback in immature and adult female rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Retardation of preovulatory desensitization to negative oestrogen feedback: mechanism of the effect of progesterone in 5-day cyclic rats.

Recent studies have shown that oestrogen can induce desensitization to its own gonadotrophin-inhibiting effect in female rats by an action on the medial preoptic area (MPOA). Probably as a consequence of this action, sensitivity to the negative oestrogen feedback declines markedly between metoestrus and dioestrus of the 4-day ovarian cycle. To study this desensitization process in 5-day cyclic rats, females exhibiting regular 5-day vaginal cyclicity were ovariectomized on consecutive days of the cycle, injected with oestradiol benzoate (OB) or oil on the day of ovariectomy and autopsied 24 h after the injection. Estimation of the serum concentration of LH revealed that desensitization to negative oestrogen feedback occurred only between day 2 of dioestrus and pro-oestrus, i.e. 2 days later than in females with a 4-day cycle. In the latter animals, an injection of progesterone in metoestrus or early dioestrus, which induced lengthening of the ovarian cycle for 1 day, delayed the onset of desensitization to a degree similar to that found in spontaneously 5-day cyclic rats. In acutely ovariectomized females, progesterone implants placed in the MPOA, but not those located in the mediobasal hypothalamus, increased the LH-inhibiting effect of low doses of OB. The results suggest that the prolonged secretion of progesterone recorded in 5-day cyclic rats retards follicle maturation and delays the forthcoming ovulation by acting, at least partly, on the MPOA and antagonizing the desensitizing effect of oestrogen. In this way, inhibition of gonadotrophin secretion by oestrogen is enhanced and the increase in tonic LH secretion necessary for the completion of follicle maturation is retarded.

Animals↗

[Conservative therapy of prostate cancer using Turisteron].

Turisteron is an orally highly effective depot estrogen (ethinylestradiol sulfonate) with relatively slight side effects. The treatment with Turisteron is very effective and is well tolerated by the patient. A strong antiandrogenic effect could be produced which had as its sequel a significant increase of the survival rates of patients with carcinoma of the prostate gland. The weekly dosage of 2 mg Turisteron led to a decrease of the biologically active, free testosterone to less than 2% compared with the initial value. The decrease of the total testosterone to castration values and the decrease of the free testosterone still significantly below values of castration are evidences for the strong antiandrogenic effect in exclusive estrogen treatment with Turisteron. From this conclusions relevant to practice were derived and finally therapy recommendation for the conservative treatment of the carcinoma of the prostate gland were given.

Aged↗

[Behavior of LH, FSH, total testosterone, free testosterone and SHBG serum levels in the therapy of prostatic cancer with Turisteron (ethinyl estradiol sulfonate)].

45 patients with prostatic cancer were treated conservatively with Turisteron at a dosage of 2 mg per week. After 2 months the serum levels of total testosterone were reduced to castration values and thereafter furthermore to 6% of the pretreatment values. The free testosterone (FT) serum level did show a decrease to 2%, while the binding capacity of the sexual hormone binding globulin (SHBG) was increased from 4,1% to 97,9%. The serum levels of the two gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were decreased only to nearly 20% of the pretreatment value. The investigations confirm the definite "antiandrogenic" effect of Turisteron, which is 10-times higher than the antigonadotropic effect.

Ethinyl Estradiol↗

[Inhibition of the free, biologically active testosterone level by Turisteron in patients with prostate cancer].

Apart from their antigonadotropic effect oestrogens also directly inhibit the androgen secretion of the testicles. Thus, on the 20th day of treatment the LH-level after 12 g diethylstilbestrol diphosphate (DSDP) decreases only to approximately 50% of the initial value, while the whole testosterone (T), however, is reduced to less than 5%. The sexual hormone binding globulin is significantly more increased (p less than 0.001) by the estrogen treatment than after orchidectomy only. Therefore, the free, biologically active T-level in the plasma consists of more than one third of the level after exclusive orchidectomy. The treatment with the depot estrogen Turisteron is clarly superior to the usual treatment Oestrasid implants. Both with and without orchidectomy the free testosterone level is significantly lower than after Oestrasid implants plus orchidectomy. Therefore, this therapy can successfully be used in the treatment of the carcinoma of the prostate also without orchidectomy.

Administration, Oral↗

Some methodic aspects in optimizing the radioimmunoassay of beta-endorphin.

A specific double antibody radioimmunoassay (RIA) for human beta-endorphin (beta-EP) using an antibody to synthetic beta h-endrophin was established. This antibody cross-reacted with beta-Lipotropin (beta-LPH) at 42 per cent on molar basis and allowed a usable range of 20 pg to 4 ng of beta-endorphin per ml in the assay. Comparing the efficiency of the conventional extraction procedures under various conditions using Corning glass, Vycor glass, QUSO G-32, silicic acid and controlled pore glass 75, the optimal result was obtained by Corning glass, with a recovery rate of more than 80 per cent. The most simple and rapid method with an extraction efficiency of more than 90 per cent was found to be the extraction by use of Sep-Pak C18 cartridges. The separation of beta-endorphin from beta-LPH was studied using Sephadex G-50, G-75, G-100 and Bio-Gel P-60 columns and different elution media. The use of a Sephadex G-50 column (0.9 X 55 cm) and elution with 0.1 N acetic acid-0.05 per cent HSA gave the best result. The reliability of the radioimmunoassay was shown under physiological and pathophysiological conditions.

Chromatography, Gel↗

[Importance of immunohistochemistry for neuro-oncology. IV. Distribution model of beta human chorionic gonadotropins in intracranial germ cell tumors].

beta-Human choriogonadotropic hormone (beta-HCG) is considered a good marker for trophoblastic differentiation of germ cell tumors. 34 primary intracranial germ cell tumors (15 germinomas, 6 mature teratomas, 1 embryonal carcinoma, 2 endodermal sinus tumors and 10 mixed germ cell tumors) were immunohistochemically evaluated for the presence of beta-HCG positive cells. In 8 of 15 germinomas and 6 of 10 mixed germ cell tumors beta-HCG cells were demonstrable. In the germinomas such cells included both syncytiotrophoblastic and mononuclear cells which histologically did not correspond to the cytotrophoblast. In one case the patient had exhibited a precocious puberty. Of the 6 beta-HCG positive mixed germ cell tumors, two contained elements of choriocarcinoma. In the cytotrophoblasts of the choriocarcinoma regions, beta-HCG was only sparsely demonstrable. Both of these patients had manifest precocious puberty clinically. The advantage of immunohistochemical demonstration of the beta-HCG compared to conventional histology is in the definite identification of trophoblastic differentiation, in particular the exact recognition of the choriocarcinoma segments, which can be critical for the prognosis. Demonstration of isolated syncytiotrophoblasts and beta-HCG positive mononuclear cells in the seminomas is of no prognostic significance and is primarily of theoretical interest.

Adolescent↗