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Biomedical subjects

P Günzel

Publications and source records attributed to P Günzel.

13 recordsLinked to original sources

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

Effect of intratracheal and oral application of corticosteroids on the adrenal function test in beagle dogs after ACTH-stimulation.

The effect of synthetic corticosteroids given intratracheally or orally on the adrenal glands of beagle dogs was investigated. The adrenal function was evaluated using a standardized ACTH stimulation test. In addition, histological and morphometrical examinations of the adrenal cortex were performed at the end of the study. Beclomethasone dipropionate given intratracheally at daily dose levels of 0.05, 0.1 and 0.5 mg/kg body weight led to a dose dependent adrenal suppression on the basis of plasma cortisol concentration and eosinophil counts after ACTH stimulation and size of zona fasciculata and reticularis. A complete adrenal suppression was observed at the highest dose level of 0.5 mg/kg body weight. Also the oral administration of 0.1 mg/kg body weight/day of beclomethasone dipropionate had a definite adrenal suppressive effect comparaable to that of 0.1 mg/kg body weight given intratracheally. However, intratracheal administration of fluocortin butylester, a local antiinflammatory drug but systemically a nearly ineffective corticosteroid (2 X 8 mg/kg body weight/day) had no suppressive effect on the adrenal gland of the beagle dog, even after a 320 times higher dose.

Administration, Oral

Effect of fluocortin butylester and beclomethasone dipropionate on the adrenal gland in beagle dogs.

The effect of butyl-6 alpha-fluoro-11 beta-hydroxy-16 alpha-methyl-3,20-dioxo-1,4-pregnadien-21-oate (fluocortin butylester, Vaspit) administered intratracheally and of beclomethasone dipropionate given intratracheally or orally on the adrenal glands of beagle dogs was investigated. The adrenal function was evaluated using a standardized ACTH stimulation test including eosinophil counts 5 h after a single i.v. injection of 0.02mg (approximately 2 IU) ACTH/kg body weight were found as well as the histological and morphometrical examination of the adrenal cortex. The cortisol determination (with Clark's method) 1.5 h and eosinophil counts to be the optimum indices for the evaluation of adrenal function. Beclomethasone dipropionate given intratracheally at daily dose levels of 0.05; 0.1 and 0.5 mg/kg body weight lead to a dose dependent adrenal suppression on the basis of plasma cortisol concentration, eosinophil counts after ACTH stimulation and size of zona fasciculata and reticularis. A complete adrenal suppression was observed at the highest dose level of 0.5 mg/kg bw. Also the oral administration of 0.1 mg/kg bw./day of beclomethasone dipropionate had a definite adrenal suppressive effect comparable to that of 0.1 mg/kg bw. given intratracheally. However, intratracheal administration of fluocortin butylester even after a 320 times higher dose (2 X 8 mg/kg bw./day) had no suppressive effect on the adrenal gland of the beagle dog.

Adrenal Glands

Effect of cyproterone acetate on prolactin secretion in the female Rhesus monkey.

Adult female rhesus monkeys were given cyproterone acetate orally in doses of 0.04, 0.4, 4 and 40 mg per kg per day for 12 weeks. Its effects were assessed on serum prolactin (PRL) concentration, the morphology of the PRL cells, and the development of the mammary glands. Serum PRL was relatively unchanged in the control animals from the fourth through the twelfth weeks of the study. In contrast, PRL was significantly elevated in each group of drug-treated animals during the same time periods. There was no development of the mammary glands nor was there any evidence of milk secretion in the control animals; however, in the monkeys given cyproterone acetate the mammary glands had extensive lobuloalveolar growth and milk-like secretion that could be expressed as early as the fourth or fifth week of the study. By immunocytochemistry and differential light microscopic staining techniques, the PRL cells in the pituitary glands of the experimental animals were found to be more numerous and much larger than those present in the controls. They displayed a well developed Golgi complex and had an abundance of cytoplasmic RNA. These data suggest that PRL secretion is markedly enhanced by cyproterone acetate.

Animals

Isolation and identification of 15-beta-hydroxy cyproterone acetate as a new metabolite of cyproterone acetate in dog, monkey and man.

15-beta-hydroxy cyproterone acetate could be identified by thin layer chromatography, mass spectrum, NMR and IR spectrum as a major unconjugated metabolite of cyproterone acetate in plasma and urine of dog, monkey and man. This metabolite has been found to interferein the Mattingly method for the determination of 11-hydroxy-corticosteroids which suggests, that this method is inadequate in controling the adrenal function of subjects treated with cyproterone acetate.

Animals

[Histochemical and histological investigations on the vagina of the beagle she-dog during various functional conditions (author's transl)].

Histotopochemistry and histology of vaginal epithelium in female beagles were studied during oestrus, metoestrus-dioestrus, post partum period and at days 20, 30, 40, 50, 60 of pregnancy. During oestrus the epithelium is uniform throughout the whole vagina: it presents itself as a high, uncornified, stratified squamous epithelium with some glycogen and lipid droplets but devoid of leucocytes. The intercellular gaps of the stratum intermedium give strong reactions for ATPase and alkaline phosphatase. The activities of oxidoreductases studied decrease continuously from basal to apical. During gravidity, post partum period and metoestrus-dioestrus distinct morphological and histochemical differences can be stated between the cranial and caudal vaginal portions. Caudal vaginal epithelium outside oestrus remains of stratified squamous type. It exhibits strong mucification during pregnancy. The PAS-positive mucous substances prefer a position in the enlarged intercellular gaps of stratum intermedium and superficiale. During pregnancy the epithelium is relatively rich in acid and completely devoid of alkaline phosphatases. Outside oestrus the epithelium of the cranial vaginal region is a relatively flat, stratified columnar one and contains leucocytes with regularity. Also the cranial vaginal portion undergoes mucification during pregnancy with a maximum about day 33. The mucous material is situated intracellularly and not within the intercellular gaps. Further, larger intraepithelial mucus cysts are observed. Alkaline phosphatase is found during gravidity in the basal region and an adluminal border of the epithelium. The reactions for oxidoreductases are strongest in the columnar cell layer which shows more functional adaptations than the remainder of the epithelium. Histochemical tests for beta-D-glucuronidase and leucine aminopeptidase give negative results in the whole vagina during all different functional stages studied.

Animals

[Cytological and immunocytochemical studies of the anterior pituitary gland of the beagle bitch during various reproduction phases].

The changes in anterior pituitary (AP) of pregnant and lactating dogs as compared with pituitary of animals in metestrus-anestrus phase are described with special reference to the relative proportion, topography and morphology of prolactin cells, somatotrophs, corticotrophs, thyrotrophs and gonadotrophs. For demonstration of these cells, suitable histological, histochemical and immunoenzyme cytochemical methods are used. The prolactin cells show progressive hyperplasia during pregnancy, so that at the end of this phase and during lactation, they comprise the most predominant glandular cells in AP. At the same time, they reveal massive hypertrophy with marked morphological features of high secretory activity, After transient or continous interruption of the suckling stimulus they show signs of functional inhibition on involution. The corticotrophs appear at 20. and 30. days of pregnancy to be relatively increased in number. While in the last third of pregnancy and during lactation, they only seem to be more active than those in pituitary of metestrus-anestrus dogs. The somatotrophs appear to be progressively reduced in relative number during pregnancy and lactation. However, they show some morphological signs of active secretion. The thyrotrophs did not show any morphological alterations during the different reproductive phases. The gonadotrophs reveal during pregnancy, especially at 30. day morphological signs of stimulation. On the contrary they appear atrophied during lactation. This may be a result of suckling stimulus and morphological expression of the inverse relationship in the secretion pattern of gonadotrophins and prolactin in dogs during suckling. The estrogen and progesterone levels in plasma as well as the changes in their relative concentrations may largely account for the structural changes on AP of pregnant dogs. However, neuroendocrine reflexes (e.g. suckling stimulus) seem to be of a great importance for the maintainance of stimulation of prolactin cells during lactation.

Adrenocorticotropic Hormone