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Biomedical subjects

F Neumann

Publications and source records attributed to F Neumann.

At least 91 records · Page 5Linked to original sources
PubMed1983

Pharmacological basis for clinical use of antiandrogens.

UNLABELLED: The first antiandrogen which was also of clinical interest--cyproterone acetate (CPA)--was discovered at the beginning of the 60th. CPA acts in all target organs for androgens and in principle affects all functions which are governed or influenced by androgens under physiological or pathophysiological conditions. EXAMPLES: Accessory sexual gland function and spermatogenesis are inhibited, there is a loss of libido in most species, the onset of puberty and bone maturation is delayed, sebaceous gland function and lipogenesis is inhibited, androgen mediated steps in male sexual differentiation do not occur. CPA is also a highly effective progestrogen and it inhibits gonadotrophine secretion. The progestational partial effect is especially important for the use of this drug in women in the treatment of certain dermatological disorders. CPA has certain glucocorticoid-like properties in animals. In humans these effects were only seen under high-dose therapy of children with precocious puberty (greater than 80 to 100 mg/m3 body area) but never in adults. Proven indications for CPA: Prostatic carcinoma, precocious puberty, hypersexuality and sexual deviations, androgenization in women (hirsutism, acne, seborrhoea oleosa, alopecia androgentica).

Androgen Antagonists↗
PubMed1982

Phenotypic modulation of the canine prostate after long-term treatment with androgens and estrogens.

Fine structural alterations of the canine prostate induced by long-term treatment of castrated adult animals with estrogens and/or androgens and also in combination with antiandrogens and/or antiestrogens for six months have been studied with particular respect to their topographic location within the gland. Three major patterns of structural responses of the epithelium have been distinguished: squamous metaplasia, atrophy, and hypertrophy, while in stroma, regression, hypertrophy, or sclerosis were observed. In addition to cellular alterations of stromal fibrocytes and smooth muscle cells, characteristic changes in the arrangement, distribution, and pattern of the different stromal elements occurred. General squamous metaplasia of the epithelium and regressive alterations of stromal cells were most obvious in animals treated with estradiol plus androstanediol. Atrophy of the epithelium and stromal sclerosis were the salient features of antiandrogen-treated castrated animals, while hypertrophy or hyperplasia of both the epithelium and stroma was a major finding in androstanediol-substituted castrated animals. Combined treatment caused rather heterogeneous structural patterns seemingly dependent on the location within the gland. The results indicate that the prostatic epithelial cells dispose of a broad variety of structural reaction patterns that, in case of combined hormonal treatment, are expressed in a manner typical for their locations within the ductal system of the gland. However, with the exception of combined treatment with estradiol, tamoxifen, and androstanediol of castrated dogs, none of the experimental protocols used induced a morphologic response of the gland comparable to that seen in human benign prostatic hyperplasia. The canine prostate therefore is of rather limited value as a model for human BPH.

Androgens↗
PubMed1982

Comparison of the antispermatogenic effects of a new D-homo-steroid and testosterone in rabbits.

In comparison to testosterone, 18 beta-hydroxy-18 alpha-methyl-16 alpha-methylene-D-homo-5 alpha-androstane-3-one (D-homo-S) shows more pronounced anti-gonadotrophic than androgenic properties in rats. The present study was initiated in rabbits to investigate the potential of D-homo-S to suppress spermatogenesis. D-homo-S in sesame oil was administered at the doses of 0.1 (DI), 3 (D II) or 10 mg (D III) per rabbit each day for 8 weeks. During treatment serum testosterone, sperm concentration and quality of sperm motility decreased, whereas sex drive, semen volume and seminal plasma concentrations of fructose and zinc were not changed in any of the groups. Testicular weight and intratesticular testosterone concentration decreased significantly in groups D II and D III, while weights of accessory sex glands increased in those groups. Testosterone in the same dose regimen did not suppress sperm count, motility or serum testosterone, however, seminal plasma zinc concentration in group T III and fructose in group TI increased. Testicular weight and intratesticular testosterone concentration decreased in group TIII only. On the other hand, the weight of the accessory sex glands increased in the same group. In conclusion, D-homo-S suppresses spermatogenesis and increases accessory sex gland weights at doses, when testosterone is still ineffective. Thus, in rabbits D-homo-S appears to be a more potent androgen than testosterone but a dissociation between antigonadotrophic and androgenic properties could not be observed.

Animals↗
PubMed1982

Effects of the antioestrogen tamoxifen on steroid induced morphological and biochemical changes in the castrated dog prostate.

The effect of the antioestrogen tamoxifen (TA) was investigated in different types of steroid-induced benign prostatic hyperplasia (BPH) in the castrated dog by histological, histochemical and biochemical analysis. A 6 months treatment with oestradiol-17 beta (E2) alone resulted in cystic and stromal hyperplasia and squamous epithelial metaplasia with a striking prostatic weight increase DNA and RNA content of the total glands increased significantly. The histochemical results and zinc values indicated the loss of normal epithelial function due to metaplatic transformation. The E2 induced cystic and metaplastic hyperplasia was prevented by TA while the stromal proliferation was significantly decreased but not abolished. Biochemical determinations revealed an effect similar to castration. After combined treatment with E2 and 3 alpha-androstanediol (3 alpha-diol) TA completely suppressed squamous metaplasia. A 3 alpha-diol induced glandular proliferation, monitored by a positive histochemical reaction, and significantly elevated zinc, DNA and RNA contents prevailed. A partial stromal stimulation indicates stimulating effects of 3 alpha-diol too on the stroma. The antioestrogenic effects of tamoxifen on experimentally induced BPH mainly manifest at the E2 induced epithelial alterations. The abolishing effects at the stromal level are distinct but not so impressive.

Androstane-3,17-diol↗
PubMed1982

Microautoradiographic studies on distribution of 5 alpha-dihydrotestosterone, cyproterone acetate and oestradiol-17 beta in human prostatic hyperplasia tissue transplanted to juvenile rats.

While maintaining the actual conditions prevailing in benign prostatic hyperplasia (BPH) in man, transplantation of BPH tissue to new born rats proved a suitable model for examining the distribution of sexual hormones in different tissue compartments of BPH. In combination with the microautoradiographic method, it was possible to demonstrate the residence of the radio-active androgen 5 alpha-dihydrotestosterone (5 alpha-DHT), the antiandrogen cyproterone acetate (CA) and the oestrogen oestradiol-17 beta (E2) in the epithelium and/or stroma of human BPH tissue. Quantitative evaluation in the form of a point per area count on photographic pictures yielded a silver grain distribution ratio in epithelium and stroma of 1.3: 1 and 1.5: 1 for epithelium to stroma after administration of [3H] 5 alpha-DHT and [3H]CA administration respectively and 0.5: 1 after [3H]E2. The high tracer recovery rate throughout the stroma following E2 administration supports the current view that the stromal proliferation is attributable mainly to oestrogen influences. The relatively high silver particle proportion throughout the stroma following 5 alpha-DHT administration corroborates recent findings which suggest that the exclusive androgen dependency of the glandular epithelium can only be considered in conjunction with an active metabolization of androgens in the stroma. The correspondence in the distribution of the radioactive tracer after [3H] 5 alpha-DHT and [3H]CA administration both in the epithelium and stroma suggest that an antagonism may also exist in the stroma.

Aged↗
PubMed1981

Morphometric analysis of prostates in castrated dogs after treatment with androstanediol, estradiol, and cyproterone acetate.

We studied the prostates of 22 beagle dogs by light morphometric analysis under defined hormonal influences. Prostatic weight increased with 3 alpha-androstanediol (3 alpha-diol) alone and in combination with 17 beta-estradiol (E2). Two different prostatic hyperplasia models were established. 3 alpha-Diol brings about diffuse glandular prostatic hyperplasia with an absolute increase of glandular parenchyma and, together with E2, provokes stromal hyperplasia with squamous metaplasia of the epithelium and secondary cyst formation. In both models, the antiandrogen cyproterone acetate causes a significant reduction of the absolute and relative volumes of the glandular compartment with antiandrogenic effects on the stroma.

Androstane-3,17-diol↗
PubMed1980

Antibodies against testosterone: valuable tools for the investigation of the hypothalamo-pituitary-gonadal system in the rabbit fetus.

16 female rabbits were actively immunized against testosterone (T). 9 of them conceived and gave birth to 89 neonates. In all neonatal plasma samples antibodies against T were detected. In the males the plasma T levels were elevated 1,000-fold. The testes of these animals were examined by means of morphometrical and biochemical methods. The results indicate increased stimulation of Leydig cells in fetuses exposed to antibodies against T, and suggest that even in the fetus a negative feedback is acting between testes and hypothalamo-pituitary system, which is interrupted by the antibodies which bind and inactivate T.

Animals↗
PubMed1980

Effects of cyproterone acetate on experimentally induced canine prostatic hyperplasia. A morphological and histochemical study.

The effect of 3 alpha-androstanediol (3 alpha-diol), 17 beta-estradiol (E2) and cyproterone acetate (CA) on prostates in castrated beagle dogs were investigated by histological and histochemical examinations. A significant increase of prostatic weight occurred after 6 months' treatment with 3 alpha-diol alone and in combination with E2. Histologically and histochemically, two different types of prostatic enlargement were observed: first, administration of 3 alpha-diol resulted in diffuse glandular hyperplasia with replacement of functional activity monitored by strongly positive reactions for acid phosphatase, aminopeptidase and zinc. Second, 3 alpha-diol plus E2 produced stratified squamous metaplasia with cystic lumina and loss of the typical morphological structure. These glands showed negative reactions for acid phosphatase, aminopeptidase and zinc. In both types of prostatic hyperplasia CA abolished epithelial or metaplastic proliferation and induced atrophy of glandular epithelium. In estrogenized dogs activation of the fibromuscular stroma was obvious. CA prevented prostatic hyperplasia by atrophying epithelial effects.

Acid Phosphatase↗
PubMed1980

Disturbances in sexual differentiation of rat foetuses following spironolactone treatment.

Pregnant rats were treated with 40 mg spironolactone (sp) po from the 13th to the 21st day p.c. The foetuses were prepared and histologically examined on day 22. The male foetuses showed distinct signs of feminization especially of the external genitalia. The anogenital distance was nearly 48% shorter than that of the controls. The prostatic utricle persisted more distinctly, and the number and size of the prostatic buds were significantly reduced. The degree of feminization of the male foetuses which is achieved under the influence of sp (40 mg/day) is the same as that which can be induced by 1--3 mg cyproterone acetate.

Animals↗
PubMed1979

Evaluation of effects of sexual steroids on the hypothalamic-pituitary system of animals and man.

Specific neuroendocrine regulatory mechanisms in rats and mice are known to be involved in the development of pituitary tumours (prolactinomas) in systemic tolerance and carcinogenicity studies of oestrogens, certain progestagens and their combinations. However, the susceptibility of the strain used seems to be of decisive importance. High doses of oestrogens may also, in special cases, stimulate development of PRL cell hyperplasia and tumours in humans. In other species such as the hamster long-term treatment with oestrogens results in hyperplastic and neoplastic changes in MSH-producing cells of the pars intermedia of the pituitary gland. On the other hand, in the dog and monkey, steroid-related pituitary tumours were not observed, in spite of long-term treatment with high doses of oestrogens, progestagens and their combinations. The capability of certain progestagens to stimulate canine GH secretion seems to play a major role as mediator of the species-specific progestagen-induced changes (mammary tumours, diabetes- and acromegalic-like syndrome) in the beagle dog. These progestagens also seem to have, in addition to their antigonadotrophic properties, an inhibitory effect on CRH-ACTH and TRH-TSH activity in the beagle bitch. These effects can be demonstrated in both the hypothalamic-pituitary system and in the corresponding peripheral target organs. These findings in the dog were not comparable to the situation in other species including man. The extent to which all these results in different species are applicable to other species depends on whether their neuroendocrine control systems are qualitatively and/or quantitatively similar. The physiological significance of the different pituitary hormones, sensitivity of target organs as well as a certain genetic disposition in the different species should also be considered. All these factors can vary from species to species. From these facts, it can be easily appreciated that results of experiments on different species with a substance possessing the same quality of biological effect in these species (e.g., oestrogen, progestagen, etc.) can only be compared when the experimental procedure takes account of the effect of this substance on the neuroendocrine system of the different species, and when dosage, mode of administration and period of treatment are correspondingly matched to the physiological conditions of each species.

Animals↗
PubMed1979

Estrogenic partial effect of norethisterone enanthate in relation to tumor induction in rat mammary gland.

The tumorigenic effect of norethisterone enanthate (NE) on mammary glands in rat and mouse may be ascribed to its own inherent estrogenicity, which is especially pronounced in these species. Because of the estrogenic partial effect, NE stimulates tubulo-alveolar growth of rat mammary gland intensively as does an estrogen-progesterone combination. Although prolactin is known as one of the essential factors needed for development of rat mammary gland, NE causes only a slight increase in serum prolactin level in the rat. In contrast with rat and mouse, NE exerts only a progestational effect in the rabbit. Since the estrogenicity of NE has not been found in many clinical studies, the estrogenic partial effect of NE seems to have no significance in humans. Such a species difference is finally due to the fact that the optimal dose ratio between estrogens and progesterone for maintenance of physiological functions of target organs is quite different from species to species.

Animals↗
PubMed1979

Role of the pituitary gland in experimental hormonal induction and prevention of benign prostatic hyperplasia in the dog.

The antiandrogen, cyproterone acetate (CPA), prevents development of prostatic hyperplasia, induced in castrated dogs by a 6 month-treatment with 5 alpha-androstane-3 alpha, 17 beta-diol (A)alone or in combination with 17 beta-oestradiol (E2). The immunoperoxidase technique was used to study functional cell types in the pars distalis of the pituitary gland and to detect growth hormone (GH) and prolactin (PRL) target sites in the prostate gland. Homologous radioimmunoassays for estimation of serum canine GH and PRL concentrations were also performed. Treatment with the combinations A + E2 and A + E2 + CPA resulted in morphological indications of stimulated GH and PRL cells and depressed gonadotrophs. This correlates well with an increase in PRL-dependent staining in glandular epithelium and fibromuscular tissue of the prostate gland. However, basal serum PRL and GH levels were not significantly affected. Treatment with A and A + E2 stimulated, while additional treatment with CPA clearly suppressed adrenocorticotrophin/melanotrophin (ACTH/MSH) cells. These findings indicate that an endocrine imbalance in hypothalamic-pituitary-adrenal function may be involved in induction and prevention of prostatic hyperplasia in the dog.

Androstane-3,17-diol↗