Biomedical subjects

G Dörner

Publications and source records attributed to G Dörner.

At least 19 recordsLinked to original sources

PubMed1992

Dehydroepiandrosterone (DHEA) levels in patients with prostatic cancer, heart diseases and under surgery stress.

DHEA levels in patients with prostatic cancer were significantly lower, but total and free testosterone (T) significantly higher as those in an age-matched control group. Therefore, the calculated quotients DHEA/free T and DHEA/T were especially different between both groups. DHEA and DHEAS levels in patients with heart diseases were also significantly lower but cortisol (F) levels were significantly higher as those in a control group. The quotients DHEA/F and DHEAS/F were also of greater significance between both groups than the hormone values alone. The response of DHEA and F levels in patients undergoing surgery showed an increase of both steroids under surgery. On the second postoperative day, however, F levels were still significantly higher but DHEA levels were significantly lower as the initial values. The differences between the initial values and those on the second postoperative day of F and DHEA showed a significant correlation, i.e. the higher the elevation of F levels above the initial values the greater was the diminution of DHEA levels below the initial values.

Adult↗

PubMed1992

Lifelong enhanced diabetes susceptibility and obesity after temporary intrahypothalamic hyperinsulinism during brain organization.

Newborn male Wistar-rats received bilateral intrahypothalamic insulin-agar-implants on the 2nd or 8th day of life. In male control animals only the insulin-free indifferent agar-vehicle was implanted at the same age. In both experimental groups with temporary intrahypothalamic hyperinsulinism during brain organization the following results were obtained: 1) Higher body weight gain starting at the end of the hypothalamic differentiation period and continuing during juvenile life until adulthood, resulting in increased relative body weight as a sign of obesity; 2) A tendency to basal hyperinsulinaemia in juvenile and adult age; 3) Impaired glucose tolerance in adulthood; 4) Increased diabetes susceptibility to a single "subdiabetogenic" dose of streptozotocin in adult age. In view of these and previous observations a teratogenetic role of high insulin concentrations during the organization of glucoregulatory hypothalamic structures is hypothesized and the possible relevance of such hyperinsulinism as a predisposing factor for a lifelong enhanced diabetes and/or obesity risk is suggested.

Animals↗

PubMed1992

Obesity and enhanced diabetes and cardiovascular risk in adult rats due to early postnatal overfeeding.

To investigate possible permanent consequences of an early postnatal overfeeding, the following experimental model was used: Male Wistar rats were divided into three groups after birth: (1) Small litters with 3-4 newborns (overnutrition), (2) normal litters with 12 animals (normonutrition), and (3) large litters with 20-24 newborn rats (undernutrition). After weaning all animals had free access to tap water and standard pellet diet. The serum insulin level of animals from small litters on day 15 of life was highly significantly increased as compared to the other groups. These overfed hyperinsulinaemic rats showed a higher body weight gain during the suckling period trough juvenile life until adulthood, associated with enhanced mean food intake and resulting in an increased relative body weight (per body length) as a sign of obesity. The obesity was found to be correlated with basal hyperinsulinaemia and increased systolic blood pressure in the small-litter-adults. Moreover, the early postnatally overnourished animals developed an increased type I-like diabetes susceptibility to a "subdiabetogenic" dose of streptozotocin in adulthood. These results suggest once more that hyperinsulinism during brain differentiation, in the present experiment induced by early postnatal overnutrition, may represent a predisposing factor for the development of obesity, of increased diabetes susceptibility and also of increased cardiovascular risk in later life.

Animals↗

PubMed1991

Short- and long-term effects of a dopamine agonist (lisuride) on sex-specific behavioural patterns in rats.

Lisuride induces in juvenile male and especially in female rats a significant increase of the male-typical initiating activity in tests on social play-fighting behaviour. In neonatally castrated as well as in prenatally stress exposed males, castrated in adulthood, which exhibit under androgen substitution alone bisexual or even predominantly heterotypical sexual behaviour, additional treatment with lisuride resulted in a temporary normalization of sexual orientation in the homotypical male direction, limited to the duration of treatment. In castrated androgen-treated females, lisuride induces a partial conversion of sexual orientation to the heterotypical male direction. When intact newborn females or neonatally castrated males were treated with lisuride during the early postnatal differentiation period of the brain (day 2-12) or, on the other hand, during the peripuberal maturation period (day 26-40), it was found that early postnatal as well as peripuberal activation of the dopaminergic system in females resulted in permanent partial masculinization of sexual orientation. Comparable trends were observed after peripuberal androgen administration in females. In neonatally castrated males, the demasculinized play-fighting as well as the sexual orientation could be normalized--at least in part--by early postnatal or peripuberal lisuride administration. These findings confirm once more our previous reports that neurotransmitters can act directly as organizers of the brain. This holds true not only for the differentiation period but also for the maturation period of the brain.

Androgens↗

PubMed1991

Effect of an acute maternal stress on the fetal hypothalamo-pituitary-adrenal system in late gestational life of the rat.

We investigated in this study the response of the fetal hypothalamo-pituitary-adrenal (HPA) system during an acute maternal stress in rats, in order to find out a possible role of developing fetal hypothalamus and to correlate its function to the androgen unbalance during the critical period of sex-specific brain differentiation. Pregnant rats of days 18-22 of gestation were subjected to an acute forced immobilization, and plasma levels of corticosterone (B) and ACTH were measured in mothers and fetuses. Hypothalamic contents of CRH and beta-endorphin (EP), pituitary content of ACTH, and plasma levels of B and ACTH were measured in mothers and fetuses under the maternal stress on day 20 of gestation. By an acute exposure to the 20 minutes' stress, plasma levels of B and ACTH elevated significantly in mothers on each day of gestation. A significant increase of fetal plasma ACTH was detected from day 18 in males, and from day 20 in females. During the maternal stress on day 20 of gestation, hypothalamic contents of CRH and EP decreased significantly in male and female fetuses, when plasma levels of B and ACTH elevated significantly. These results indicate that fetal HPA axis seems to actually respond to the maternal stress during the late gestational period. Further, a release of CRH under the stress together with an activation of EP system in the fetal hypothalamus suggests a possible mechanism regulating the androgen secretion by the fetal hypothalamus via changes of the LH levels.

Adrenocorticotropic Hormone↗

PubMed1991

The influence of fetal adrenals on the androgen levels during brain differentiation in human subjects and rats.

Measurements of plasma total and free testosterone (T) levels in human subjects from fetal to postpubertal life showed about twofold higher total T and 15-fold higher free T levels in female fetuses than in female adults. The ratios between the sexes were only moderate in fetal life. Between the 17th and 31st week of pregnancy the ratios (male:female) of total T were found to be 6.6 in week 17, 1.5 in week 22, 2.3 in week 28 and 1.2 in week 31 of pregnancy compared to 16.2 in adulthood. The corresponding ratios of free T were calculated to be 5.6 in week 17, 1.4 in week 22, 0.9 in week 28 and 0.7 in week 31 of pregnancy compared to 34 in adulthood. In amniotic fluids, we measured even an overlapping of T values between the two sexes. The reason for the observed striking difference of T levels between the sexes in fetal and postpubertal life may be the high adrenal activity and secretion rate in fetal life during brain differentiation. In rats, the contribution of adrenals to plasma T levels is only moderate and much smaller than in human beings. As measured in adult female rats, the portion was found to be about 20% only, contrary to about 60% in women. The main sources of T in female rats appear to be the gonads. The mainly gonadal secretion may be the reason that exposure of pregnant rats to stress diminished the T levels in male fetuses, but did not significantly elevate the T levels in females.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1991

Gene- and environment-dependent neuroendocrine etiogenesis of homosexuality and transsexualism.

Sexual brain organization is dependent on sex hormone and neurotransmitter levels occurring during critical developmental periods. The higher the androgen levels during brain organization, caused by genetic and/or environmental factors, the higher is the biological predisposition to bi- and homosexuality or even transsexualism in females and the lower it is in males. Adrenal androgen excess, leading to heterotypical sexual orientation and/or gender role behavior in genetic females, can be caused by 21-hydroxylase deficiency, especially when associated with prenatal stress. The cortisol (F) precursor 21-deoxycortisol (21-DOF) was found to be significantly increased after ACTH stimulation in homosexual as compared to heterosexual females. 21-DOF was increased significantly before and even highly significantly after ACTH stimulation in female-to-male transsexuals. In view of these data, heterozygous and homozygous forms, respectively, of 21-hydroxylase deficiency represent a genetic predisposition to androgen-dependent development of homosexuality and transsexualism in females. Testicular androgen deficiency in prenatal life, giving rise to heterotypical sexual orientation and/or gender role behavior in genetic males, may be induced by prenatal stress and/or maternal or fetal genetic alterations. Most recently, in mothers of homosexual men--following ACTH stimulation--a significantly increased prevalence of high 21-DOF plasma values and 21-DOF/F ratios was found, which surpassed the mean + 1 SD level of heterosexual control women. In homosexual men as well--following ACTH stimulation--most of the 21-DOF plasma values and 21-DOF/F ratios also surpassed the mean + 1 SD level of heterosexual men. In only one out of 9 homosexual males, neither in his blood nor in that of his mother increased 21-DOF values and 21-DOF/F ratios were found after ACTH stimulation. In this homosexual man, however, the plasma dehydroepiandrosterone sulfate (DHEA-S) values and the DHEA-S/1000 x A (A = androstenedione) ratio were increased before and after ACTH stimulation. Furthermore, highly significantly increased basal plasma levels of dehydroepiandrosterone sulfate were found in male-to-female transsexuals as compared to normal males, suggesting partial 3 beta-ol hydroxysteroid dehydrogenase deficiency to be a predisposing factor for the development of male-to-female transsexualism.

Environment↗

PubMed1990

Escherichia coli DNA polymerase I: inherent exonuclease activities differentiate between monofunctional and bifunctional adducts of DNA and cis- or trans-diamminedichloroplatinum(II). An exonuclease investigation of the kinetics of the adduct formation.

[3H]dGMP-3'-labelled, activated salmon testis DNA and [32P]dGMP-5'-labelled open circular M13 DNA were reacted with cis-diamminedichloroplatinum(II), cis-diamminechloroaquaplatinum(II), cis-diamminediaquaplatinum(II) or trans-diamminechloroaquaplatinum(II). The reaction was arrested after arbitrary times by adjustment to slightly alkaline solution conditions. The platinum-containing DNA was digested with Escherichia coli DNA polymerase I. The progress of nucleotide release was measured by acid precipitation of undigested DNA. Solubilized nucleotides and adducts were analyzed by HPLC. The 3'-5'-exonuclease activity liberated single-coordinated dGMP-platinum(II) adducts from both cis- and trans-platinum(II) treated salmon testis DNA and a small fraction of adducts of cis-platinum(II) that coordinated two molecules of dGMP. The bisadduct was derived from non-neighboring guanine residues probably located at or close to 3'-termini. This nuclease activity neither cut between nor after neighboring guanine residues crosslinked by cis-platinum(II). No bisadduct was liberated for trans-platinum(II). The 5'-3'-exonuclease activity did not liberate any nucleotide adducts from cis-platinum(II)-treated DNa. However, it removed single-coordinated guanine adducts of trans-diamminedichloroplatinum(II). From the kinetics of the appearance of dGMP monoadducts and the inhibition of digestion, a reaction scheme is formulated for the reaction of platinum(II) complexes with DNA that confirms and extends the previously published one [W. Schaller, H. Reisner & E. Holler (1987) Biochemistry 26, 943-950]. The longevity of the dGMP monoadduct intermediate is discussed in the context of the efficiency of cis-diamminedichloroplatinum(II) as an antitumor drug.

Animals↗

PubMed1990

Increased cell-mediated cytotoxicity against beta-cells in streptozotocin-treated offspring of mother animals with gestational hyperglycaemia.

The offspring of mother animals with mild gestational hyperglycaemia exhibited basal hyperinsulinism, decreased glucose tolerance and increased susceptibility to streptozotocin diabetes. Following low-dose successive streptozotocin treatment a significantly increased spleen cell cytotoxicity against beta-cells was found in these animals as compared to the offspring of gestational normoglycaemic control mothers. Such increased cell-mediated cytotoxicity, considered as enhanced autoimmune reactivity, was positively correlated to blood glucose levels and negatively correlated to pancreatic insulin contents. Thus, hyperinsulinism, occurring during pre- and neonatal brain organization and produced by gestational hyperglycaemia, is a predisposing teratogenetic risk factor not only for the development of type II, but also of type I diabetes. Thus, it is comprehensible that the prevalence of type I diabetes in children could be decisively reduced by preventing gestational hyperglycaemia in their mothers (Dörner et al., 1985).

Animals↗

PubMed1990

Perinatal hyperinsulinism and perinatal obesity as risk factors for hyperinsulinaemia in later life.

In the offspring of gestational or long-term diabetic mothers the following findings were obtained: (1) Immunoreactive plasma insulin levels on the first day of life were weakly correlated to the thickness of the skin-fold at the neck on the third day of life (n = 82; r = 0.27; P less than 0.05). (2) A significant correlation was found between the plasma insulin levels at birth and the basal as well as the maximal plasma insulin values after glucose loading (1.75 g/kg b. wt.) at 2 years of age (for basal values: n = 25; r = 0.53; P less than 0.01; and for maximal values: n = 21; r = 0.63; P less than 0.01). (3) A highly significant correlation was even observed between the thickness of the neck-fold at 3 days of age and the fasting plasma insulin levels at 3-8 years of age (n = 26; r = 0.61; P less than 0.001). These findings suggest that perinatal hyperinsulinism and perinatal obesity, induced by maternal hyperglycaemia and/or overnutrition during pregnancy, are risk factors for persistent hyperinsulinaemia predisposing to diabetes mellitus and cardiovascular disease in later life.

Child↗

PubMed1990

Early postnatal overfeeding and diabetes susceptibility.

Milk intake of suckling rats was controlled by adjusting little size at birth to maximum (small litter, overnutrition), ten (normal litter, normal nutrition) or about 19 (large litter, undernutrition) pups. After weaning all animals received the same diet ad libitum. Overnutrition before weaning resulted in an early postnatal hyperinsulinaemia, decreased glucose tolerance and increased susceptibility to streptozotocin-induced diabetes in adulthood. However, the preweaning undernutrition seemed to have no preventive effect on diabetes susceptibility in adulthood. The study suggested that early postnatal overnutrition, which is associated with an early postnatal hyperinsulinemia, can increase diabetes susceptibility in adult life.

Animals↗

PubMed1990

Evidence that desensitization of the negative feedback of oestrogen and priming for the positive feedback of oestrogen depend upon a common mechanism of oestrogen action in rats.

Oestrogen priming of the central nervous system is required for the positive feedback of oestrogen, and the sensitivity of the negative feedback of oestrogen can be reduced by oestrogen itself. Using adult female and male rats we examined the possibility that these effects depend upon a common mechanism of oestrogen action that is mediated by the medial preoptic area (MPOA). Guide cannulae were implanted in the MPOA of 4-day cyclic rats which were ovariectomized during the evening of day 1 of dioestrus. Glass capillary tubes containing different substances were placed in the cannulae between 09.00 and 12.00 h on the presumptive day 2 of dioestrus. The effectiveness of oestrogen priming was evaluated by examining whether an s.c. implant of oestradiol-17 beta (OE2) induced an LH surge, and the inhibitory effect of oestrogen on tonic LH secretion was investigated by injecting the rats with 3 micrograms oestradiol benzoate (OB)/100 g body weight. The priming effect of an s.c. implant of OE2 could be imitated by the bilateral implantation in the MPOA of a mixture of OB and cholesterol at a ratio of 1:360 for 3 h only. Similar medial preoptic oestrogen implantation also significantly reduced the LH-inhibiting effect of OB. In accord with findings obtained in former studies on desensitization of the negative oestrogen feedback, oestrogen priming resulting from the s.c. administration of OE2 could be suppressed by short-term medial preoptic implantation of clomiphene citrate or apomorphine; bilateral electrical stimulation of the medial amygdaloid nucleus induced an increase in the serum concentration of LH in ovariectomized females implanted with OB in the MPOA, but not in castrated males pretreated and implanted with OB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Hormone-dependent brain development and neuroendocrine prophylaxis.

During the pre- and/or early postnatal life, systemic hormones and neurotransmitters are acting as organizers of the brain, which is the controller of the neuro-endocrine-immune system. Thus, the quantity of systemic hormones and neurotransmitters codetermines during critical periods of brain development the quality, i.e., the responsiveness, of their own central nervous controllers and hence the functional and tolerance ranges of their own feedback control systems throughout life. Abnormal levels of systemic hormones and neurotransmitters, which can be induced by abnormal conditions in the psychosocial and/or natural environment, can act as teratogens and lead to permanent physiological and/or psychological dysfunctions in later life. Thus, many deviations and malfunctions of reproduction, metabolism, information processing and immunity called up to now idiopathic, essential, cryptogenic, primary or genuine can be explained by abnormal pre- and/or early postnatal psycho- and/or physiological processes. Therefore, "structural teratology" (teratomorphology) was supplemented by "functional teratology" (teratopsychophysiology). Such deviations, dysfunctions or diseases based on abnormal brain development can widely be prevented either by optimizing the psychosocial and/or natural environment or by well-timed correcting abnormal concentrations of systemic hormones and/or neurotransmitters.

Animals↗

PubMed1989

Influence of a dopamine agonist (lisuride) on sex-specific behavioural patterns in rats. I. Short term effects.

Lisuride induces in juvenile male and especially in female rats a significant increase of the initiating activity in tests on social play-fighting behaviour. In neonatally castrated as well as in prenatally stress exposed males, castrated in adulthood, which exhibit under androgen alone bisexual or even predominantly heterotypical sexual behaviour, additional treatment with lisuride resulted in a temporary normalization of sexual orientation in the homotypical male direction. In castrated androgen treated females, lisuride induces a partial conversion of sexual orientation to heterotypical male direction.

Animals↗

PubMed1989

Influence of a dopamine agonist (lisuride) on sex-specific behavioural patterns in rats. II. Long-term effects.

Intact female and neonatally castrated male rats were treated with the dopamine agonist/serotonin antagonist lisuride during the early postnatal differentiation period of the brain (Day 2-12) or during the peripuberal maturation period (Day 26-40). It was found that early postnatal as well as peripuberal activation of the dopaminergic system in females resulted in masculinized social play-fighting behaviour, and lisuride application as late as peripuberally resulted in permanent masculinization of sexual behaviour. Comparable trends were found after peripuberal androgen administration. On the other hand, the demasculinized social play fighting as well as the sexual behaviour of neonatally castrated males, which is usually bisexual or even predominantly heterotypical, could be normalized--at least in part-by early postnatal or peripuberal lisuride administration. These findings confirm once more our previous reports that neurotransmitters can act directly as organizers of the brain. This holds true not only for the differentiation period but also for the maturation period.

Animals↗

PubMed1989

Oestrogen priming for the positive oestrogen feedback: site of action.

The significance of oestrogen priming for efficacy of the positive, ovulation-inducing oestrogen feedback has been known for more than 15 years, but the site and mechanism of oestrogen action in the priming effect have not yet been elucidated. Long-term ovariectomized adult female rats were injected once or twice with 20 micrograms oestradiol benzoate (OB), and the serum LH concentration was estimated. Whereas a single injection of OB induced significant inhibition of LH secretion, high circulating LH levels were recorded in rats injected twice with the hormone at an interval of 48 h. This increase was prevented in ovariectomized females fitted with guide cannulae, if the antioestrogen clomiphene citrate was implanted into the medial preoptic area (MPOA) before the first injection of oestrogen and removed prior to the second. On the other hand, replacement of the first oestrogen administration by the implantation of a very low dose of OB into the MPOA resulted in stimulation of LH secretion. OB implants placed into the hypothalamic ventromedial-arcuate region were ineffective in this regard. Taken together, the findings suggest that the priming effect of oestrogen is mediated in rats, at least in part, by the MPOA.

Animals↗

PubMed1989

Suppression of plasma androgen levels with a combination therapy of depot-estrogen (Turisteron) and Dexamethasone in patients with prostatic cancer.

Treatment of patients with prostatic cancer with a combination of 1-2 mg depot-estrogen (ethinylestradiol sulfonate = Turisteron) per week and 1 mg dexamethasone per day suppressed the mean testosterone (T) level to 2.8% (0.53 nmol/l), the free T to 0.8% (1.9 pmol/l) and the adrenal androgens (AA) -- androstenedione (A), dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) -- to more than 40% of the initial values. Treatment with Turisteron alone (2 mg per week) did not change the DHEA and DHEAS levels but decreased plasma A concentration to 65% (2.96 nmol/l) of the initial values.

Aged↗

PubMed1989

The value of cw-Doppler ultrasonography and DSA in the diagnosis of extra- and intracranial stenosis--a comparison with intraoperative findings.

The use of cw-Doppler sonography and digital subtraction angiography (DSA) for diagnosis of cerebro-vascular insufficiency (CVI) was evaluated in a retrospective study. 113 findings obtained by DSA and 315 findings obtained by cw-Doppler sonography were compared to the corresponding intraoperative finding. Furthermore, we examined the incidence of accompanying intracranial stenoses of the carotid artery. The impact of these stenoses on the CVI stage was analyzed by means of 200 transcranial Doppler sonographic studies. Cw-Doppler sonography (sensitivity: 95%) was clearly superior to DSA (sensitivity: 70%) for diagnosis of high grade and subtotal stenoses of the internal carotid artery (ICA). Sensitivity of both methods was insufficient for diagnosis of low grade stenoses (cw-Doppler: 50%, DSA 25%). Analysis of 200 transcranial Doppler sonographic studies did not reveal pathologic changes of intracranial vessels in 67% of all cases. This finding did not depend on the condition of the extracranial vessels and did also not depend on the CVI stage. Additionally, there was no correlation between the incidence and degree of intracranial stenoses and the CVI stage or the degree of stenosis of the ICA. These results support the view that Doppler sonography is the method of choice for diagnosis of high grade stenoses of the carotid artery. The use of DSA is limited to cases in which kinking or occlusion is suspected. Additional intracranial changes did not correlate with the CVI stage.

Angiography↗