Effect of testosterone on the kinetics of the development of suppressor cells in adjuvant arthritis

Summary The induction of unresponsiveness to mycobacterial adjuvant took a longer time in male DA rats than in female rats. A shift in the induction time of unresponsiveness in males toward the female type was brought about by castration, but could be reverted to the male type by the application of testosterone. The transfer study revealed that cells capable of preventing arthritis required a longer incubation time for their development in males than in females. This suggests that testosterone inhibits the development of suppressor cells in adjuvant arthritis.Acknowledgments. We are grateful to The Naito Foundation Research Grant for 1983.     

Sex difference in polyethylenglycol-induced thirst

Summary The polyethylenglycol-induced thirst in male and female castrated rats has been studied. The polyethylenglycol (PG) increases the water intake more in females than in males. Estradiol benzoate and testosterone P. diminishes the amount of water drunk after PG treatment in the females, but not in the males.     

Hormonal regulation of a new female-specific serum protein (FP) of the laboratory rat

Summary This paper reports evidence for a hormonal regulation of a new rat serum protein (female specific protein, FP) which is only demonstrable in female rats. Male and female rats were treated with testosterone and estrogen. The FP was assayed with immunological methods. The following results were obtained: 1. In testosterone-treated females the serum level of FP is reduced significantly. 2. In estrogenized males the FP was distinctly demonstrable but not in the control males.     

Hormonal induction of steroid sulphatase in the mouse

By comparing steroid sulphatase levels per se, and also ratios to alpha-galactosidase, in 6 sets of mice - normal females, entire and castrated males both with and without exogenous testosterone administration - we obtained support for the contention that induction of this enzyme is in part controlled by male hormones.     

Maturation of the female Tetrix undulata (Swrb) (Orthoptera, Tetrigidae): influence of the male and copulation:parthenogenetic egg-laying]

The percentage of laying females and laying time, are compared between mature females (diapause break by chilling) and diapause strain females (diapause not broken by chilling) reared with mature male or diapause male or without male. For the same physiological state of the females (mature or diapause) there is no difference in the percentage of females laying, when they are reared with mature male or with diapause one or none; but the laying time is shortest with mature male, longer with male in diapause, even longer without male. Parthenogenetic egg-pods can be obtain. Rearing with mature males does not break the reproductive diapause of females. In parthenogenetic egg-pods the number of eggs is short for low diapause females; greater for mature ones and greatest for females with strong diapause broken by a corpus allatum implant of mature female of Locusta migratoria. Corpus allatum of the low diapause strain of females of Tetrix undulata have less activity than that of mature females. Few parthenogenetic eggs develop, even less hatch. In Tetrix undulata parthenogenesis is accidental.     

Effects of castration, estradiol and testosterone on tubulin levels of the medial basal hypothalamus and the adenohypophysis of the rat.

Tubulin levels of the medial basal hypothalamus (MBH) were greater in male than in female rats. Orchidectomy brought about a decrease of MBH tubulin concentration, whereas testosterone injection augmented it in the MBH and adenohypophysis. Estradiol administration augmented MBH tubulin and protein concentration.     

Effect of actinomycin D or puromycin on microsomal testosterone hydroxylase activity enhanced by testosterone in female rat liver

Summary The injection of testosterone propionate for 4 successive days into female rats resulted in an increase of the in vitro conversion of the hydroxylated testosterones from testosterone by the hepatic microsomal, fraction, but no change in the content of microsomal cytochrome P-450 occurred. Actinomycin D or puromycin, which was administered for 4 days with injections of testosterone propionate, prevented the enzyme induction.     

Effects of catalase,peroxidase, superoxide dismutase and 10 scavengers of oxygen radicals in carrageenin edema and in adjuvant arthritis of rats

Summary Catalase, peroxidase and superoxide dismutase were found to inhibit significantly carrageenin edema and the primary phase of adjuvant arthritis in rats after i.v. injection. Heat-inactivated enzymes were as effective as the native enzymes. None of 10 scavengers of oxygen radicals inhibited the adjuvant arthritis at any time. Accordingly, no evidence for a participation of oxygen radicals in the secondary arthritis phase could be found, whereas a role of oxygen radicals in the primary arthritis phase and in carrageenin edema cannot be ruled out.     

Synergism between long-acting bromocryptine microcapsules and cyclosporine A in the prevention of various autoimmune diseases in rats

Pre-treatment of male Sprague-Dawley rats with long-acting bromocryptine microcapsules (CBLA) significantly inhibited the arthritic response to Freund's complete adjuvant and reduced weight loss, thymolysis, splenomegaly and leukocytosis. In the prevention of adjuvant arthritis (AA), the combination of CBLA plus sub-optimal doses of cyclosporine A (CsA) was more efficient than either of the drugs alone. Sub-optimal doses of CsA were 0.1 and 1.0 mg/kg/day s.c. for 5 days. Furthermore, CBLA alone did not decrease the incidence of experimental allergic uveitis (EAU) in the male Lewis rats. Low-dose CsA reduced the incidence of uveitis by 50%, and with the addition of CBLA, 100% of rats were protected. Low-dose CsA was 2 mg/kg/day i.m. for 14 days. Long-term treatment of male Sprague-Dawley rats with CBLA alone reduced the incidence and severity of spontaneous autoimmune periateritis nodosa (PN) in a dose-dependent manner; CsA was less potent than CBLA, and only additive effects were obtained. Finally, for the prevention of spontaneous autoimmune insulin-dependent diabetes (DM), the administration of CBLA did not improve the effect of a low-dose CsA in male BB rats. Nevertheless, a delay in onset of DM could be achieved. A sequential therapy using CsA plus CBLA clearly showed beneficial effects. The dose of CsA was 10 mg/kg p.o. 6 days/week for 21 weeks. Compared with Sprague-Dawley or Lewis male rats, BB male rats showed only weak prolactin suppression after the same doses of CBLA. It is suggested that the use of CBLA may be particularly beneficial in autoimmune disorders. The effectiveness of the combination therapy CBLA plus CsA, however, was dependent on the model considered. Various factors could play a role: (1) the different ways of administering CsA (s.c. in AA, i.m. in EAU and PN, oral in DM); (2) strain-dependency in the capacity of CBLA to suppress Prl secretion; and(3) at least in the BB rats, the transient increase of CsA bioavailibility which was possibly induced by CBLA.     

Absorption of iron from gut into blood: Sex- and time-related studies in rats

Summary As judged from 2-h blood level curves, adult female rats absorbed more Fe^II per cm² of gross duodenal mucosa than adult male rats. By contrast, the 2-h blood level curves per cm² of mucosa of proximal jejunum did not differ significantly in male and female rats although in both sexes, iron was absorbed more efficiently from the duodenum. This research was supported by grant RO1 AM 12381 from the National Institute of arthritis, Diabetes and Digestive and Kidney Diseases, National Institutes of Health.     

Anti-interleukin-1 and anti-tumor necrosis factor-alpha synergistically inhibit adjuvant arthritis in Lewis rats

Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) play dominant roles in mediating the progression of many inflammatory joint diseases, including rheumatoid arthritis in humans, collagen-induced arthritis in mice and rats, and adjuvant arthritis in rats. Blockade of either cytokine partially controls these diseases. The present study investigated the value of combination anti-cytokine therapy in arthritis: the efficacy of IL-1 receptor antagonist (IL-1ra) and 30 kDa polyethylene glycol (PEG)-conjugated soluble TNF receptor type I (PEG sTNF-RI) given together was assessed in Lewis rats with adjuvant arthritis. Administration of either IL-1ra or PEG sTNF-RI partially alleviated joint inflammation, loss of bone mineral density, and loss of body weight. In contrast, combination of these anti-cytokine treatments exhibited a synergistic capacity to inhibit these changes, even when combining doses of IL-1ra and PEG sTNF-RI that did not affect lesion severity when used alone. Statistical analysis of these adjuvant arthritis data using the isobologram method proved that IL-1ra and PEG sTNF-RI were clearly synergistic in inhibiting inflammation, loss of bone mineral density, loss of body weight, and histopathologic parameters of inflammation and joint destruction. These results suggest that treating autoimmune arthritic diseases with combinations of anti-IL-1 and anti-TNF molecules will achieve superior efficacy compared to the use of a single class of anti-cytokine agent and may allow for dose reductions that could prove useful in minimizing potential side effects.     

Levels of testosterone and dihydrotestosterone in guinea pig sex canals during embryonic life]

At the undifferentiated stage, testosterone and dihydrotestosterone levels were comparable in sexual ducts of both sexes. An hormonal sexual dimorphism appeared at the time of differentiation: while testosterone rapidly decreased in the female ducts, it considerably increased in those of the male. Testosterone rather than DHT seems to be responsible for the wolffian duct stabilization in the male foetus.     

Hormonal induction of steroid sulphatase in the mouse

Summary By comparing steroid sulphatase levels per se, and also ratios to -galactosidase, in 6 sets of mice — normal females, entire and castrated males both with and without exogenous testosterone administration — we obtained support for the contention that induction of this enzyme is in part controlled by male hormones.     

Ursachen der geschlechtsunterschiedlichen MilchdrÜsengewebsentwickiung bei Ratten

Summary Under the same hormonal conditions, mammary gland growth in adult female rats is more pronounced than in males. Since there are no differences in the glandular development of both sexes, either at birth or at 30 days of life, it is assumed that male rats react less sensitively than female rats in response to a hormonal stimulus with regard to mammary gland growth. It is presumed that androgen influence during the differentiation stage is responsible for the fixation of a decreased sensitivity of the positive feedback-mechanism between estrogens and prolactin secretion in males. Thus changes in sensitivity would be the reason for mammary gland growth in males being smaller than in females under the same hormonal conditions.

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Dieser Arbeit liegen zum Teil die Untersuchungsergebnisse einer SchÜler-Facharbeit von U.Rieser zugrunde.     

Effects of castration,estradiol and testosterone on tubulin levels of the medial basal hypothalamus and the adenohypophysis of the rat

Summary Tubulin levels of the medial basal hypothalamus (MBH) were greater in male than in female rats. Orchidectomy brought about a decrease of MBH tubulin concentration, whereas testosterone injection augmented it in the MBH and adenohypophysis. Estradiol administration augmented MBH tubulin and protein concentration.This study was supported in part by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina (CONICET) (grant No. 6638), and the Programa Latinoamericano de Investigación en Reproducción Humana (PLAMIRH 2.3.1.75 R).     

Influences of the submaxillary gland of male mice on the immune response to sheep red blood cells

Summary Removal of the submaxillary gland (SMG) from male but not female mice caused a suppressed immune response to sheep red blood cells. Administration of a SMG saline extract from male mice to SMG-ectomized males restored the suppressed response to control levels. This suggests that the male mouse SMG contains a factor(s), possibly of an endocrine nature, capable of influencing cells involved in an immune response.     

Zinc,copper and selenium in reproduction

Of the nine biological trace elements, zinc, copper and selenium are important in reproduction in males and females. Zinc content is high in the adult testis, and the prostate has a higher concentration of zinc than any other organ of the body. Zinc deficiency first impairs angiotensin converting enzyme (ACE) activity, and this in turn leads to depletion of testosterone and inhibition of spermatogenesis. Defects in spermatozoa are frequently observed in the zinc-deficient rat. Zinc is thought to help to extend the functional life span of the ejaculated spermatozoa. Zinc deficiency in the female can lead to such problems as impaired synthesis/secretion-of (FSH) and (LH), abnormal ovarian development, disruption of the estrous cycle, frequent abortion, a prolonged gestation period, teratogenicity, still-births, difficulty in parturition, pre-eclampsia, toxemia and low birth weights of infants. The level of testosterone in the male has been suggested to play a role in the severity of copper deficiency. Copper-deficient female rats are protected against mortality due to copper deficiency, and the protection has been suggested to be provided by estrogens, since estrogens alter the subcellular distribution of copper in the liver and increase plasma copper levels by inducing ceruloplasmin synthesis. The selenium content of male gonads increases during pubertal maturation. Selenium is localized in the mitochondrial capsule protein (MCP) of the midpiece. Maximal incorporation in MCP occurs at steps 7 and 12 of spermatogenesis and uptake dereases by step 15. Selenium deficiency in females results in infertility, abortions and retention of the placenta. The newborns from a selenium-deficient mother suffer from muscular weakness, but the concentration of selenium during pregnancy does not have any effect on the weight of the baby or length of pregnancy. The selenium requirements of a pregnant and lactating mother are increased as a result of selenium transport to the fetus via the placenta and to the infant via breast milk.     

Lymphocyte subpopulations in adjuvant arthritis of rats. Effects of corticoids and gamma irradiation]

Experimental model of human chronic inflammatory arthritis, adjuvant arthritis may be induced only in several strains of inbred Rats: it is well developed in LEW and practically absent in WAG. After adjuvant injection, the PHA-stimulable lymphocytes subpopulation quite disappears from the blood, if polyarthritis is well developed. These cells are probably capted in the tissues implicated in immunological conflict. On the contrary, the ConA-stimulable subpopulation is enhanced in both strains after adjuvant injection, earlier and more intense in WAG than in LEW and that phenomenon is probably linked to a stimulation of suppressor T lymphocytes. Treatment with prednisone or gamma rays inhibits partially and delays the appearance of arthritis in LEW, acting essentially on ConA-stimulable subpopulation.     

Hormonal manipulation of carrageenin-induced pyresis in rats

Summary The intensity of the hyperthermic response in rats promoted by subplantar injection of 1 mg of carrageenin is directly related to the irritant properties of the type of carrageenin. The overall pyretic response is more dramatic in female rats than in male rats. Subtle changes in the time-course hyperthermic profiles are seen after hormonal modifications.This work was supported by NIH, MBS research grant No. RR08111.     

Influence of age on epidermal growth factor receptor level in the rat brain

The influence of age on 125I-epidermal growth factor (EGF) binding to rat brain plasma membranes was investigated. The specific binding of EGF to membranes decreased gradually with age in both male and female rats. There was no significant difference in the specific binding between males and females. Scatchard analysis of the binding data showed that the decrease in EGF binding with age was due to a decrease in the number of EGF receptors.