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Biomedical subjects

G Dörner

Publications and source records attributed to G Dörner.

At least 109 records · Page 6Linked to original sources

Varying sensitivity to the negative oestrogen feedback during the ovarian cycle of female rats: evidence for the involvement of oestrogen and the medial preoptic area.

The gonadotrophic response to a single injection of oestradiol benzoate (OB) was studied in acutely ovariectomized adult rats during the different stages of a 4-day ovarian cycle. The results showed a sudden decline of the sensitivity to the gonadotrophin-inhibiting effect of OB between metoestrus and dioestrus. This desensitization to the negative oestrogen feedback was probably caused by an oestrogen action on the medial preoptic area (MPOA). In rats ovariectomized and implanted with OB in the MPOA in metoestrus, an s.c. injection of OB on the presumptive day of pro-oestrus did not lower the circulating LH and FSH levels, whereas a clear suppression of gonadotrophin secretion was seen in females implanted with cholesterol in the MPOA or implanted with OB in the hypothalamic ventromedial-arcuate region. Similar findings were obtained in rats which had been ovariectomized 3-4 weeks before implantation. A final experiment demonstrated that bilateral lesioning of the MPOA also reduced the sensitivity to the negative feedback action of oestrogen in long-term ovariectomized rats. In all experiments performed, diminution of the oestrogen-induced inhibition of LH secretion was more marked than that of suppression of FSH secretion. It is proposed that desensitization to the negative oestrogen feedback, probably resulting from an inhibitory oestrogen action on medial preoptic neurones, is a prerequisite for adequate gonadotrophic support of preovulatory follicle maturation in the presence of a continuously rising oestrogen concentration in the blood.

Animals↗

[Significance and mechanism of desensitization to the gonadotropin-inhibiting effect of estrogen. 1. Studies on prepubertal desensitization].

In immature female rats, both a distinctive diminution of the gonadotrophin-inhibiting effect of s. c. or intrahypothalamically implanted estradiol and a simultaneous rise of the estrogen and gonadotrophin levels in the blood were revealed during the last days preceding the onset of puberty. Based on these findings, studies on the neurohormonal mechanism underlying this prepubertal desensitization to the negative estrogen feedback were performed. Bilateral lesioning of the medial preoptic area (MPOA) which induced precocious puberty also diminished significantly the gonadotrophin-inhibiting effect of s. c. or intrahypothalamically administered estrogen. Similar responses were recorded following the implantation of very low quantities of estrogen into the MPOA, whereas medial preoptic implants of the antiestrogen clomiphene citrate impaired the spontaneous prepubertal desensitization and delayed the onset of puberty. It is concluded from the results that the prepubertal increase of the estrogen concentration in the blood itself induces the desensitization to estrogen by an inhibitory effect on medial preoptic neurons. Preliminary clinical and experimental findings suggest that a comparable mechanism may be operative in humans, too.

Animals↗

Hormone-dependent brain development.

Hormones may be defined as chemical messengers that are produced in specialized cells and exert biological effects on other cells of the same organism by acting either locally (as local hormones) or on distant target cells (as systemic hormones). Hence, neurotransmitters may be regarded as local hormones of the brain, and two different hormonal actions can be distinguished for neurotransmitters as well as for systemic hormones: (1) transient, i.e. reversible activational or inactivational effects and (2) persistent, i.e. more or less irreversible differentiational or organizational effects, if the hormones act during critical developmental periods, especially of the brain. Abnormal levels of systemic hormones and neurotransmitters produced by genetic defects or deficient environments and occurring during brain differentiation can act as 'teratogens'. They lead to malorganizations of the brain and permanent dysfunctions of fundamental processes of life, such as reproduction, metabolism, and/or information processing. Such malorganizations of the brain appear to be preventable by improving the external environment and/or by diagnosing and correcting abnormalities of systemic hormones and neurotransmitters during brain development. These principles of 'teratophysiology and teratopsychology' open new possibilities for preventive therapy.

Animals↗

Stressful events in prenatal life of bi- and homosexual men.

One hundred bi- or homosexual men as well as 100 heterosexual men of similar age were asked about maternal stressful events that may have occurred during their prenatal life. A significantly increased incidence of prenatal stress was found in bisexual and, particularly, in homosexual men. This finding suggests that prenatal stress in males may represent a risk factor for the etiogenesis of sexual deviations in later life.

Adult↗

Prevention of demasculinization and feminization of the brain in prenatally stressed male rats by perinatal androgen treatment.

Female rats were exposed to immobilization and illumination stress from day 15-22 of pregnancy. Their male offspring showed demasculinization, i.e. significantly decreased male sexual behaviour, and feminization, i.e. significantly increased female sexual behaviour, in adulthood. This permanent demasculinization and feminization of the brain, induced by prenatal stress, could be prevented by perinatal androgen treatment.

Androgens↗

The influence of adrenaline on plasma testosterone in adult and newborn male rats.

In adult male intact and adrenalectomized rats a significant decrease of plasma testosterone was found following five days of subcutaneous treatment with adrenaline. LH was significantly decreased in adrenalectomized, adrenaline treated males. Plasma testosterone was also found to be diminished in the male offspring of females treated with adrenaline during pregnancy. In view of these findings catecholamines may also play a role in the stress-induced drop of plasma testosterone in adult animals as well as in the production of androgen deficiency in male fetuses and newborns of stress-exposed pregnant females.

Adrenalectomy↗

Effects of tamoxifen on the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), 17 beta-oestradiol (E2), total and free testosterone (T) and total and free dihydrotestosterone (DHT) in blood of patients with benign prostatic hyperplasia.

Treatment of 9 patients with benign prostatic hyperplasia with 20 mg tamoxifen daily for 6 weeks resulted in a significant increase of LH (211%), FSH (215%), E2 (231%), total T (157%), free T (148%) and total DHT (148%) levels in blood. The increase of plasma free DHT (152%) levels was not significant and PRL concentrations in serum were unchanged during treatment. Comparison of the increases between total T and free T, total T and total DHT as well as free T and free DHT failed to reveal any significant differences. These results imply (1) a marked anti-oestrogenic effect of tamoxifen at the level of hypothalamo-hypophysial axis (2) no effect at the hepatic oestrogen receptor sites indicated by unchanged SHBG-bound T and DHT in plasma and (3) no significant inhibitory effect of tamoxifen on 5 alpha-reductase activity concluded from the T/DHT ratio in peripheral circulation. In view of these findings tamoxifen appears to be unsuitable for therapy of benign prostatic hyperplasia.

Dihydrotestosterone↗

Long-term effects of early postnatal nutrition on subsequently body weight gain, emotionally and learning behaviour in male rats.

Male rats have been reared as litters of 2 pups (group A) or 12 pups (group B) during the first 3 weeks of life. Males of group A exhibited higher body weights from day 10 to day 430, reached puberty at earlier age and showed lower emotionality as well as diminished learning capability and decreased memory capacity in adulthood as compared to males of group B. Furthermore, adult males of group A developed an increased ratio of insulin to glucose serum concentration at 90 minutes after glucose administration.

Animals↗

On the LH response to oestrogen and LH-RH in transsexual men.

In male rats, androgen deficiency during a critical period of sexual brain differentiation was shown to give rise to a predominantly female-differentiated brain. Such animals displayed "homosexual behaviour", i.e., they were sexually attracted preferentially to partners of the same sex. In addition, they exhibited a sex-specific evocability of a positive oestrogen feedback effect. A positive oestrogen feedback effect on LH secretion was also induced in homosexual transsexual men, in contrast to hetero- or bisexual transsexual men. Thus in homosexual transsexual men, an intravenous injection of 20 mg Presomen (Premarin) produced a significant decrease of serum LH levels followed by a significant increase above the initial LH values. In hetero- or bisexual transsexual men, by contrast, intravenous oestrogen administration, while producing a significant decrease of serum LH levels, was not followed by an increase above the initial LH values. A positive oestrogen feedback effect on LH secretion was also found in homosexual non-transsexual men, in contrast to heterosexual men. These findings suggest that transsexual as well as non-transsexual homosexual men possess a predominantly female-differentiated brain which may be based, at least in part, on androgen deficiency during sexual differentiation of the central nervous system. Homosexual transsexual men also showed an increased LH and FSH response to LH-RH as compared to hetero- or bisexual transsexual men.

Adult↗

Acute effects of maternal stress on fetal blood catecholamines and hypothalamic LH-RH content.

The acute effects of maternal stress (restraint for 20 to 140 min) on the plasma levels of epinephrine, norepinephrine and dopamine in pregnant rats and their fetuses as well as on the catecholamine content of fetal adrenals and the LH-RH content of fetal hypothalami, were investigated at day 22 of gestation. Despite of a relatively moderate increase of maternal plasma catecholamines a significant increase of norepinephrine (p less than 0.05) and dopamine (p less than 0.05) levels in plasma of the fetuses 30 min after starting maternal stress was observed. The fetal blood concentrations of catecholamines before and during maternal stress were significantly higher than those of the mothers (p less than 0.05 to p less than 0.001). A gradual decrease of the fetal adrenal content of epinephrine and norepinephrine was found, whereas an unchanged content of dopamine of fetal adrenals was registered during maternal restraining. The LH-RH content of fetal hypothalami rose significantly (p less than 0.005) 60 min after starting maternal stress and returned to initial values 140 min after starting restraining.

Adrenal Glands↗

Changes of the plasma tryptophan to neutral amino acids ratio in formula-fed infants: possible effects on brain development.

The ratio of plasma concentrations of tryptophan to the sum of neutral amino acids (valine, isoleucine, leucine, phenylalanine and tyrosine) was found to be significantly lower in formula-fed infants as compared to breast-fed infants and to newborns at birth. This tryptophan to neutral amino acids ratio in the blood is thought to control the synthesis of serotonin in the brain. Serotonin deficiency in the developing brain based on a decreased plasma tryptophan to neutral amino acids ratio may contribute to developmental obesity and/or permanent changes of mental capacity and social adaptability as observed in human subjects who had been formula-fed as compared to those who had been breast-fed in neonatal life.

Amino Acids↗

Increase of FSH secretion in immature female rats following lesioning of the medial amygdaloid nucleus.

Immature female rats were bilaterally lesioned or sham-lesioned in the anterior part of the medial amygdaloid nucleus (AMN) at 21 days of age, and the serum FSH and LH concentrations were estimated in groups of rats autopsied at daily intervals from day 21 through day 28. Whereas the LH concentration did not differ between lesioned females and the controls, a highly significant elevation of the circulating FSH level was recorded in the lesioned rats from day 22 till day 24. A further experiment demonstrated that similar lesions did not change the FSH and LH-inhibiting effect of estrogen in rats that were ovariectomized on day 22, daily injected with 0.05 microgram estradiol benzoate per 100 g b.w. on days 22 and 23, and sacrificed 24 hr after the last injection. The results suggest that the AMN exerts a restraining influence on the hypophyseal FSH secretion around 21 days of age, and that this inhibitory activity does not depend upon sensitization to the negative feed-back of estrogen.

Amygdala↗

Influence of neonatally administered dehydroepiandrosterone on reproduction of rats.

Male and female rats were injected with dehydroepiandrosterone (DHEA) from day 2 after birth to day 12 on alternate days. The inhibition of the growth of testes, seminal vesicles, adrenal glands and pituitary was found immediately after cessation of treatment. When adult, the neonatally DHEA treated males showed diminished copulatory activity. In contrast, no impairment of sexual behaviour could be found in females. However, neonatal DHEA treatment resulted in a dose dependent impairment of cyclicity in the females, accompanied by sub- or infertility. These findings suggest that DHEA shows some dissociation between its organizing influence on gonadotropin secretion and sexual behaviour.

Animals↗