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M Haug

Publications and source records attributed to M Haug.

At least 55 records · Page 3Linked to original sources

[The role of dehydroepiandrosterone and pregnenolone in the expression of stress behavior towards lactating females in mice].

Triads of castrated male mice were chronically administered with either oil vehicle or 280 nmol of dehydroepiandrosterone (D) or pregnenolone (P). They were tested for their attack on a lactating intruder female introduced in their home-cage 2, 24 or 47 hr after their last injection. D significantly reduced male aggressive behavior for at least 24 hr. Other groups of castrated males were daily treated with vehicle or 280 nmol of D, dehydroepiandrosterone sulfate (DS) or androstenediol (ADIOL), a D metabolite with clear-cut oestrogenic properties. D, but neither DS nor ADIOL, significantly reduced their aggressive responses to lactating intruders. Finally, neural levels of D, DS and testosterone (T) were measured in intact and castrated males injected with either vehicle or D. Measurable amounts of D and DS were detected, with DS being the predominant chemical form. D and DS concentrations were unchanged by castration but neural D was increased more than twenty fold in castrates treated with D, whereas DS was unchanged. The concentration of T in the brain of the intact (sham-operated) mouse approached 3 ng/g but fell close to the detection limit after gonadectomy. D treatment caused a slight but significant increase in brain T concentration in castrated mice, although T remained far below the level measured in intact males.

Aggression↗

Neuro-steroids: 3 beta-hydroxy-delta 5-derivatives in rat and monkey brain.

The rat brain accumulates pregnenolone (P) as the unconjugated steroid, the sulfate ester (S) and fatty acid esters (L). P + PS do not disappear from rat brain after combined adrenalectomy (adx) and castration (orx). PL does not serve a source of P after adx + orx. P is metabolized by several rat brain regions to progesterone and to PL. Brain microsomes contain the acyl-transferase which converts P to PL using endogenous substrates. Brain P and dehydroepiandrosterone (D) undergo a prominent circadian variation with their acrophases at the beginning of the dark span. The circadian variation of brain D persists after adx + orx. The monkey brain (Macaca fascicularis) also accumulates P and D. Adrenal suppression with dexamethasone for 4 days does not decrease the concentrations of brain P and 3rd ventricle CSFP and D. The concentrations of brain D are decreased to a much smaller extent than plasma D. D inhibits the aggressive behavior of castrated male mice exposed to lactating female intruders. This is not the case for DS or androst-5-ene-3 beta, 17 beta-diol. The D analog 3 beta-methyl-androst-5-en-17-one, which is not estrogenic and cannot be metabolized to testosterone or estradiol, is as active as D in inhibiting the aggressive behavior of castrated mice.

Adrenal Glands↗

Modulation of p53 protein expression during cellular transformation with simian virus 40.

We analyzed the relation of metabolic stabilization of the p53 protein during cellular transformation by simian virus 40 (SV40) to (i) expression of the transformed phenotype and (ii) expression of the large tumor antigen (large T). Analysis of SV40-tsA28-mutant-transformed rat cells (tsA28.3 cells) showed that both p53 complexed to large T and free p53 (W. Deppert and M. Haug, Mol. Cell. Biol. 6:2233-2240, 1986) were metabolically stable when the cells were cultured at 32 degrees C and expressed large T and the transformed phenotype. At the nonpermissive temperature (39 degrees C), large-T expression is shut off in these cells and they revert to the normal phenotype. In such cells, p53 was metabolically unstable, like p53 in untransformed cells. To determine whether metabolic stabilization of p53 is directly controlled by large T, we next analyzed the metabolic stability of complexed and free p53 in SV40 abortively infected normal BALB/c mouse 3T3 cells. We found that neither p53 in complex with large T nor free p53 was metabolically stable. However, both forms of p53 were stabilized in SV40-transformed cells which had been developed in parallel from SV40 abortively infected cultures. Our results indicate that neither formation of a complex of p53 with large T nor large-T expression as such is sufficient for a significant metabolic stabilization of p53. Therefore, we suggest that metabolic stabilization of p53 during cellular transformation with SV40 is mediated by a cellular process and probably is the consequence of the large-T-induced transformed phenotype.

Animals↗

Vitamin K1 content of maternal milk: influence of the stage of lactation, lipid composition, and vitamin K1 supplements given to the mother.

Using a sensitive electrochemical assay for vitamin K1 and standardized techniques for breast-milk collection, we studied the vitamin K1 content of human milk during the first 5 wk of lactation with respect to 1) individual and interindividual differences, 2) the relationship of vitamin K1 to other lipids, and 3) the influence of oral supplements of vitamin K1 on breast milk concentrations. Comparison of fore and hind milk from the mothers revealed higher vitamin K1 concentrations in hindmilks, suggesting that the lipid content influences the vitamin K1 concentration in maternal milk. Samples of maternal milk from nine mothers collected from day 1 to day 36 of lactation showed significantly higher vitamin K1 concentrations in colostral milk than in mature milk. For colostral milk there was a significant correlation of vitamin K1 to cholesterol (r = 0.62) but not to total lipid or phospholipid suggesting a role for cholesterol in the secretion of vitamin K1 into colostral milk. For mature milk correlation coefficients of vitamin K1 with all lipids were low (r = 0.29-0.37) suggesting that at later stages of lactation dietary fluctuations of vitamin K1 may be a more important determinant of the vitamin K1 content of breast milk than the lipid composition. To test the influence of diet, mothers were given oral supplements of vitamin K1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Biochemistry of human milk in early lactation.

With the analysis of more than 550 human milk samples we showed that triglycerides (accounting for 96-99% of the total lipids) increased from 2 to 3.5 g/100 ml mainly during the first week postpartum and remained constant thereafter. In contrast, both cholesterol and vitamin E concentrations decreased from 35 to 20 mg/100 ml and from 1.7 to 0.30 mg/100 ml, respectively. The phospholipids remained constant (40 mg/100 ml). Also the fatty acid composition of total lipids changed. Mid chain fatty acids (C10, C12, C14) increased, whereas the long chain polyunsaturated fatty acids decreased. The P/S-ratio of 0.32 remained constant throughout lactation. The mean protein content of human milk decreased from approximately 2 g/100 ml at day 2 to approximately 1 g/100 ml at day 36 of lactation. The content of each individual amino acid decreased likewise. However, when we expressed the amino acid values in relation to the protein value--that is as g amino acid per g protein--some decreased, some remained constant and some increased indicating a changing protein pattern. From these data we computer-calculated a sharp decrease in IgA content, a moderate decrease for lactoferrin and constant values for casein and a-Lactalbumin. Throughout the whole period of investigation, non protein nitrogen accounted for about 20% of total nitrogen. Although the absolute values decreased according to total nitrogen, the sum of free amino acids, as well as the amount of taurine, remained constant. Lactose increased from about 4 g/100 ml to 6 g/100 ml during the first days of lactation. The calcium content increased from a mean value of 25 mg/100 ml at day 1 to 32 mg/100 ml at day 5 and remained constant at 30 mg/100 ml up to day 36. Phosphorus content increased from 10 mg/100 ml at day 1 to 17 mg/100 ml at day 8 and then continuously decreased to 13 mg/100 ml at day 36. The protein-bound part of the calcium remained constant during the period investigation, the fat-associated part increased from 11% to 26%. Protein-bound phosphorus decreased from 45% in colostral milk to 29% in transitional and 23% in mature milk.

Amino Acids↗

Alcohol and social behaviour in group-housed female mice.

Group-housed female mice were injected IP with 0, 0.5, 1.0 or 2.0 g/kg of ethanol. Twenty min after injection, the animal's responses in a neutral cage to a docile male "standard opponent" were videotaped for 500 sec. The tapes were subsequently analysed in terms of the total times allocated by the females to non-social, social/sexual, aggressive and timid activities. The frequency of occurrence of acts and postures associated with the above categories was also determined. Similar females given the same doses were used to assess the blood alcohol concentrations 20 min after injection. Timid behaviour was greatly increased by high doses of ethanol, especially as a consequence of increases in the element 'cringe'; at the low dose 'cringe' was decreased in frequency. Social/sexual behaviour was also influenced in a biphasic manner, low doses increasing and high doses reducing such activity. The drug modified some elements of non-social behaviour in a manner suggesting motor impairment at high doses. There was no evidence that any dose of ethanol induced aggressiveness in these animals. There did not seem to be a simple dose-response effect.

Aggression↗

Effects of gender, gonadectomy and social status on attack directed towards female intruders by resident mice.

Small unisexed groups (triads) of either male of female Swiss strain mice attack lactating intruders introduced into their home-cages. Female residents are, however, generally much more aggressive towards such intruders than are males. Ovariectomy of female residents (on day 15 or day 50 of life) has little effect on such responses, but castration of male residents significantly increases their attack on lactating intruders to a level resembling that of females. The introduction of the lactating female into the home-cage of sham-operated or gonadectomized male or female residents also enhances intragroup fighting with males (irrespective of their endocrine status) being the more aggressive. Finally, the social status of the male alters the response towards lactating females. Dominants generally show higher levels of attack, an effect that can be augmented by castration.

Aggression↗

A brief review comparing the effects of sex steroids on two forms of aggression in laboratory mice.

This brief review examines the roles of sex steroids in two forms of "aggression" in laboratory mice. The social conflict induced in male mice by individual housing or reproductive experience was contrasted with the attack shown by small groups of female mice on lactating intruders. Gonadectomy of males largely abolishes the former response but actually augments the latter activity in male subjects. Testosterone, estradiol and 5 alpha-dihydrotestosterone all restore social conflict in gonadectomized male mice but these sex steroids inhibit attack on lactating female intruders by gonadectomized males. The data clearly confirm that there is no simple relationship between a particular hormone and "aggression." These forms of attack may serve very different functions even though they involve similar action patterns and distributions of bites on the attacked animal. A tentative discussion is included about the roles of these activities.

Aggression↗

Effects of naloxone administration on attack by castrated male mice on lactating intruders.

The effect of the narcotic antagonist naloxone (a mu blocker at low doses) on the attack displayed by castrated male mice towards lactating intruders was investigated. Naloxone at doses of 1 mg and 2 mg/kg decreased attacks an effect which was also evident to a lesser extent at 0.75 mg/kg. These findings suggest a role for endogenous opiates in the expression of this form of aggression although one must warn that naloxone at some of the higher doses used here can influence kappa and delta receptors as well as gabaergic activity. The interrelationships between endogenous opioids, gabaergic neurotransmission and gonadal hormones in the regulation of this attack response are discussed.

Aggression↗

Evidence for free and metabolically stable p53 protein in nuclear subfractions of simian virus 40-transformed cells.

To determine functional subcellular loci of p53, a cellular protein associated with cellular transformation, we analyzed the nucleoplasmic, chromatin, and nuclear matrix fractions from normal mouse 3T3 cells, from methylcholanthren-transformed mouse (MethA) cells, and from various simian virus 40 (SV40)-transformed cells for the presence of p53. In 3T3 and MethA cells, p53 was present in all nuclear subfractions, suggesting an association of p53 with different structural components of the nucleus. In 3T3 cells, p53 was rapidly turned over, whereas in MethA cells, p53 was metabolically stable. In SV40-transformed cells, p53 complexed to large tumor antigen (large T) was found in the nucleoplasmic and nuclear matrix fractions, as described previously (M. Staufenbiel and W. Deppert, Cell 33:173-181, 1983). In addition, however, metabolically stable p53 not complexed to large T (free p53) was also found in the chromatin and nuclear matrix fractions of these cells. This free p53 did not arise by dissociation of large T-p53 complexes, suggesting that stabilization of p53 in SV40-transformed cells can also occur by means other than formation of a complex with large T.

Animals↗

Biochemistry of maternal milk in early lactation.

The analysis of more than 550 human milk samples showed that triglycerides (accounting for 96-99 per cent of the total lipids) increased from 2 to 3.5 g/100 ml mainly during the first week postpartum and remained constant thereafter. In contrast, both cholesterol and vitamin E concentrations decreased from 35 to 20 mg/100 ml and from 1.7 to 0.30 mg/100 ml, respectively. The phospholipids remained constant (40 mg/100 ml). The fatty acid composition of total lipids showed remarkable changes. Mid-chain fatty acids (C10, C12, C14) increased, whereas the long-chain polyunsaturated fatty acids decreased. The P/S ratio of 0.32 remained constant throughout lactation. The mean protein content of human milk decreased from approximately 2 g/100 ml at day 2 to approximately 1 g/100 ml at day 36 of lactation. The content of each individual amino acid decreased likewise. However, when we expressed the amino acid values in relation to the protein value--that is as gram of amino acid per gram of protein--some decreased, some remained constant and some increased indicating a changing protein pattern. Throughout the whole period of investigation, non-protein nitrogen accounted for about 20 per cent of total nitrogen, taurine ranging at about 6 mg/100 ml. The calcium content increased from a mean value of 25 mg/100 ml at day 1 to 32 mg/100 ml at day 5 and remained constant at 30 mg/100 ml up to day 36. The mean phosphorus content increased from 10 mg/100 ml at day 1 to 17 mg/100 ml at day 8 and then continuously decreased to 13 mg/100 ml at day 36.

Amino Acids↗

Effects of ethanol on social behaviour directed towards male intruders by lactating Swiss mice.

Ethanol (0.5, 1.0 or 2.0 g/kg) was given intraperitoneally to lactating Swiss strain mice and the animal's response to a docile male intruder was assessed using a videotape analysis that estimated the time that the females allocated to non-social, social/sexual, aggressive and timid categories of response. No evidence was produced in this study that alcohol augmented aggression although conditions were certainly conducive for such an effect. Alcohol does, however, modify aspects of social behaviour in lactating female mice.

Aggression↗

Studies on the effects of dehydroepiandrosterone and its metabolites on attack by castrated mice on lactating intruders.

Triads of castrated male mice (residents) were injected each day for 2 weeks with oil vehicle or 280 nmol of dehydroepiandrosterone (D). They were tested for their attack on a lactating female (intruder) introduced in their home-cage 2,24 or 48 hr after their last injection. D significantly reduced male aggressive behavior for at least 24 hr. Other groups of castrated males were injected each day with vehicle or 280 nmol of D, dehydroepiandrosterone sulfate (DS) or androstenediol (ADIOL). D, but neither DS nor ADIOL, significantly reduced their aggressive responses to intruders. Neural levels of D, DS and testosterone (T) were measured in intact males injected with vehicle or D. The concentration of D in brain was unchanged by castration and was increased about 20 fold in D injected males. The concentration of neural T was 10 nmol/g of tissue in intact males, was almost undetectable in castrated males, and was slightly increased in D injected males. Further work will be needed to identify the steroid molecule(s) responsible for this behavioral effect of D.

Aggression↗

[Dependency of human milk lipids on length of the lactation period, time of day, nursing and maternal diet].

The dependency of the human milk lipids triglycerides (TG), cholesterol (Chol), phospholipids (PL), and the fatty acid composition of both TG and PL on the stage of lactation, the day time, the course of one nursing, and on the mother's diet was shown by analyzing more than 350 milk samples. In progressing lactation (day 1-36) TG increased from 1.9 to 3.9 g/100 ml. Chol decreased from 35 to 20 mg/100 ml, while PL remained with 40 mg/100 ml rather constant. The resulting decrease in the PL/TG- and Chol/TG-ratios indicates an increasing size of fat globules. During one nursing, TG and Chol increased four-fold and PL doubled. During the day lipids (TG, Chol, PL) of the milk of German mothers reached their peak values in the afternoon, whereas the ones of milks obtained from English mothers were found in the late evening. With 3 mothers (n = 3) carbohydrate-rich diets (65 cal%) led to an increase of the milk fat content. In contrast high fat diets (50 cal%) resulted in milks with low fat contents (2.6/4.1 g/100 ml). Chol (20.8/37.5 mg/100 ml) and PL (26.4/45.3 mg/100 ml) showed the same dependency. The fatty acid composition changed mainly dependent on the duration of the lactation and the mother's diet, but not during one single nursing and during the day. Long-chain polyunsaturated fatty acids were higher in early than in mature milks. The P/S-ratio of TG was found to remain constant in progressing lactation (0.32), whereas the one of PL increased from 0.6 to 0.71. Dependent on the regimen of the mother the P/S-ratios (n = 3) were found to be 0.27 (high carbohydrate diet) and 0.46 (high fat/high linoleic acid diet).

Breast Feeding↗

Influence of castration and brain GABA levels in three strains of mice on aggression towards lactating intruders.

This study examined the relationship among aggression towards lactating intruders, castration and brain GABA levels in three strains of mice (C57, C3H and CBA). Both C57 and C3H (but not CBA) animals showed reduced attack latencies following castration. C57 mice showed the highest intensity of this behavior and the response was almost absent in the CBA strain. Considerable strain differences in brain GABA levels were observed. In particular the most aggressive C57 castrates had significantly higher levels of GABA in the hypothalamus, the olfactory bulbs and the amygdala. Such changes are not recorded in C3H or CBA strains of mice, which are both characterized by low levels of baseline aggression towards lactating intruders.

Aggression↗