O. Dobozy

Changes in sexual behavior of adult male and female rats neonatally treated with vitamin D3

1 Neonatal treatment of rats with vitamin D3 resulted in a change of sexual behavior in adulthood. 2 2.5 mg vitamin D 3 completely inhibited the ejaculation of males without any apparent influence on sexual desire. 250 mg vitamin D3 influenced both the desire and ejaculation. 3 Sexual activity of females was depressed by both doses. 4 The experiments demonstrate that vitamin D3, a steroid in structure, given in the critical period of hormonal imprinting may influence steroid hormone-receptor commanded events for life, in a way similar to the effects exhibited by synthetic steroid hormone analo gues and benzpyrene in earlier studies.

Hepatic regeneration induces transient acute phase reaction: systemic elevation of acute phase reactants and soluble cytokine receptors.

The growth factors present during liver regeneration partially overlap with the regulators of the hepatic acute phase response. We analysed the acute phase reaction and changes in soluble cytokine receptors after partial hepatectomy, when tissue injury inducing acute phase reaction and major reduction of liver mass occur simultaneously. Three acute phase proteins and mRNAs were determined by ELISA and northern blot hybridisation in rats. Serum levels of IL‐6 and three soluble cytokine receptors (sTNF‐αR I and II, sIL‐6R) were detected by ELIBA or dot‐blot assay. Time‐course profiles of fibrinogen, α2‐macroglobulin and haptoglobin proteins and mRNA are presented. Elevation of IL‐6, soluble TNF‐α receptors and soluble IL‐6 receptor levels were also detected. The time‐course of changes in haptoglobin concentration and elevation of soluble cytokine receptors is described by this in vivo experimental system. The results show good correlation with (post)transcriptional activation of immediate and delayed early gene products. These data suggest the involvement of both acute phase proteins and soluble cytokine receptors in the regulation of liver regeneration.

Elevated hepatic glucocorticoid receptor expression during liver regeneration in rats

In rats within the first week of partial hepatectomy reconstruction of the normal histological structure of the liver already starts. To approach the possible role of endogenous glucocorticoids in the process of regeneration we measured the changes in the expression of steroid glucocorticoid receptor gene after various regeneration intervals. After partial hepatectomy, between 0.5–168 hours from the surgery, the gene expression (mRNA) of glucocorticoid receptor was determined by reverse transcription followed by PCR and normalized to that of glycerolphoshate dehydrogenase. Two peaks of glucocorticoid receptor mRNA were detected first, bet ween 3 and 6 hours (first peak) and a second between 24 and 36 hours. Immunoreactive glucocorticoid receptor was detected by immunohistochemistry using monoclonal anti-glucocorticoid receptor. Three days after the surgery immunohistochemical studies showed substantially more immunoreactive GcR protein in the regenerated liver than in the controls. These semiquantitative data provide evidence suggesting elevation of glucocorticoid receptor expression during regeneration of liver at mRNA and protein levels.

Impact of neonatal treatment with cardioactive glycosides (digoxin, ouabain) on receptor binding capacity, blood level and cardiac function in the adult rat. Extension of the imprinting theory

A single neonatal treatment with a cardioactive glycoside (ouabain, digoxin) altered the response of the adult rat to digitaloid treatment. As demonstrated by RIA, re-exposure to digoxin at 2 months of age was followed within 30 min by a more than twofold increase in serum digoxin over the not pretreated control and, although a steady concentration decrease followed, the experimental rats still had a higher serum digoxin level than the controls at 4 h. In the not presensitized control group the serum digoxin peak appeared at 60 min at a considerably lower level than the 30-min maximum of the experimental rats. Neonatal pretreatment with ouabain depressed myocardial ouabain binding, but enhanced the Na+ K+ -ATPase activity. The above differences were conspicuous in the functional response, yet a greater atrial response to the positive inotropic action of K-strophanthoside and a greater ventricular response to beta adrenergic excitation were readily seen in the experimental group. It follows that not only hormones, but also other ligands acting at receptor level can be regarded as potential inducers of imprinting.

Effect of nifedipine treatment (imprinting) of rat feti and newborns on the responsiveness of adult rat's uterus. Extension of the imprinting theory.

1. The uterus of adult progeny of rats treated with nifedipine during the late phase of pregnancy react in vitro to oxytocin less and the contractility of ones treated with higher dose (100 micrograms) disappears. 2. There is a more pronounced deficiency or lack of responsiveness in five week old animals treated with nifedipine neonatally. 3. The experiments demonstrate that perinatal imprinting can be developed not only on hormone receptors and enzymes but on ion (Ca2+) channels of the plasma membrane. Consideration of this fact might have an importance in clinical aspects too.

Effect of contraceptive treatment on thymic glucocorticoid receptors and hepatic microsomal enzyme system of adult rats.

Contraceptive steroid treatment accounted for about a 30 per cent decrease in the number of thymic glucocorticoid receptors of adult rats. Neonatal allylestrenol treatment had no influence on that treatment. The activity of the hepatic microsomal (PSMO) enzyme system was not changed by the contraceptive treatment. It appears that contraceptive treatment may account for overlaps on receptors in adulthood.