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Biomedical subjects

S E Taymans

Publications and source records attributed to S E Taymans.

30 records · Page 2Linked to original sources
PubMed1998

Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene.

Familial hyperaldosteronism type II (FH-II) is characterized by autosomal dominant inheritance and hypersecretion of aldosterone due to adrenocortical hyperplasia or an aldosterone-producing adenoma; unlike FH type I (FH-I), hyperaldosteronism in FH-II is not suppressible by dexamethasone. Of a total of 17 FH-II families with 44 affected members, we studied a large kindred with 7 affected members that was informative for linkage analysis. Family members were screened with the aldosterone/PRA ratio test; patients with aldosterone/PRA ratio greater than 25 underwent fludrocortisone/salt suppression testing for confirmation of autonomous aldosterone secretion. Postural testing, adrenal gland imaging, and adrenal venous sampling were also performed. Individuals affected by FH-II demonstrated lack of suppression of plasma A levels after 4 days of dexamethasone treatment (0.5 mg every 6 h). All patients had negative genetic testing for the defect associated with FH-I, the CYP11B1/CYP11B2 hybrid gene. Genetic linkage was then examined between FH-II and aldosterone synthase (the CYP11B2 gene) on chromosome 8q. A polyadenylase repeat within the 5'-region of the CYP11B2 gene and 9 other markers covering an approximately 80-centimorgan area on chromosome 8q21-8qtel were genotyped and analyzed for linkage. Two-point logarithm of odds scores were negative and ranged from -12.6 for the CYP11B2 polymorphic marker to -0.98 for the D8S527 marker at a recombination distance (theta) of 0. Multipoint logarithm of odds score analysis confirmed the exclusion of the chromosome 8q21-8qtel area as a region harboring the candidate gene for FH-II in this family. We conclude that FH-II shares autosomal dominant inheritance and hyperaldosteronism with FH-I, but, as demonstrated by the large kindred investigated in this report, it is clinically and genetically distinct. Linkage analysis demonstrated that the CYP11B2 gene is not responsible for FH-II in this family; furthermore, chromosome 8q21-8qtel most likely does not harbor the genetic defect in this kindred.

Aldosterone↗
PubMed1998

Structure of the gene coding for calcineurin B (PPP3R1) and mapping to D2S358-D2S1778 (chromosomal region 2p15).

Calcineurin is a protein phosphatase with an important role in signal transduction; its calcium-binding regulatory subunit, calcineurin B, is widely present in the brain and is coded by the PPP3R1 gene which was mapped recently to human chromosome 2. Calcineurin has long been considered a candidate for psychiatric and/or monogenic brain disorders. The present study reports the intron-exon structure of the PPP3R1 gene with the proximal intronic sequences, its genetic mapping to D25358-D251778 on chromosome 2p15, and its exclusion in a genetic disorder mapped proximal to this locus.

Base Sequence↗
PubMed1997

The hypothalamic-pituitary-adrenal axis of prairie voles (Microtus ochrogaster): evidence for target tissue glucocorticoid resistance.

Basal plasma corticosterone levels in prairie voles (Microtus ochrogaster) are extremely high, in the absence of any apparent negative consequences of glucocorticoid excess. We tested the hypothesis that prairie voles are a novel rodent model of target tissue resistance to glucocorticoids. Prairie voles had a significantly higher adrenal-to-body weight ratio, 5- to 10-fold greater basal plasma corticosterone, and 2- to 3-fold greater basal plasma ACTH concentrations than montane voles (Microtus montanus) and rats. While plasma corticosterone binding globulin (CBG) was 2-fold higher in prairie voles than in rats, both estimated and directly measured plasma free corticosterone were significantly higher in prairie voles than in rats. Plasma corticosterone levels in prairie voles were responsive to both circadian cues and a stressor, but were resistant to suppression by the synthetic glucocorticoid, dexamethasone (DEX). Western blots of brain and liver protein extracts, using a glucocorticoid receptor (GR) antibody, revealed the presence of a approximately 97 kDa immunoreactive band, the expected size for GR. Binding assays revealed significantly lower DEX affinity of corticosteroid receptors (CR) in cytosol of prairie vole brain and liver than that in the same tissues in rats. We conclude that prairie voles are a novel rodent model of glucocorticoid resistance, and that decreased affinity of CR for ligand might be partially responsible for this phenomenon.

Adrenocorticotropic Hormone↗
PubMed1997

Stress affects corticosteroid and immunoglobulin concentrations in male house mice (Mus musculus) and prairie voles (Microtus ochrogaster).

Glucocorticoids, secreted in response to perceived stress, can suppress immunoglobulin (Ig) levels and compromise immune function in mice and rats. Prairie voles (Microtus ochrogaster) have been reported to exhibit basal corticosterone concentrations that would cause pathological changes in the immune function of most other rodents. The goals of the present study were to verify that serum corticosterone concentrations are high in prairie voles, as compared with house mice (Mus musculus), by measuring serum corticosterone with the same RIA; to examine the effects of mild stressors on corticosterone response in both species and to examine the effects of elevated corticosterone levels on IgM and IgG levels in prairie voles and house mice. After 2 weeks of randomly timed 15-min daily restraint or cold-water swim sessions, animals were injected with sheep red blood cells. The data confirmed that basal blood concentrations of corticosterone were higher in prairie voles than house mice, but these high levels doubled after the first swim session in prairie voles, indicating that the adrenals can respond to stressors by producing increased corticosterone. After stress, antibody production (both IgM and IgG) was reduced in house mice but not in prairie voles, despite higher blood concentrations of glucocorticoids in prairie voles. Although body mass was statistically equivalent between species, prairie voles and mice differed dramatically in adrenal and splenic masses. Average adrenal mass of prairie voles was approximately three times the average mass of these organs in house mice; in contrast, the average splenic mass of house mice was approximately three times that of prairie voles. These data may be relevant to seasonal changes in immune function and survival.

Adrenal Cortex Hormones↗
PubMed1997

Deletion of a consensus oestrogen response element half-site in the glucocorticoid receptor of human multiple myeloma.

We have carried out molecular scanning of the glucocorticoid receptor (GR) of the glucocorticoid resistant multiple myeloma cell line U266. An amplified fragment from the 3' untranslated region displayed an aberrant migration by PCR-single-stranded conformational polymorphism (PCR-SSCP) analysis. The mutant allele had a deletion of an 8 base pair sequence containing a half-site of an oestrogen response element. This motif was found conserved in rat GR. This same allele lacked four As in an upstream region with 18 consecutive As in the normal allele. These mutations may affect mRNA stability or alter interactions with regulatory factors.

Estrogens↗
PubMed1996

The effects of stress on social preferences are sexually dimorphic in prairie voles.

Prairie voles (Microtus ochrogaster) are monogamous rodents that form pair bonds characterized by a preference for a familiar social partner. In male prairie voles, exposure to either the stress of swimming or exogenous injections of corticosterone facilitate the development of a social preference for a female with which the male was paired after injection or swimming. Conversely, adrenalectomy inhibits partner preference formation in males and the behavioral effects of adrenalectomy are reversed by corticosterone replacement. In female prairie voles, swim stress interferes with the development of social preferences and corticosterone treatments inhibit the formation of partner preferences, while adrenalectomized females form preferences more quickly than adrenally intact controls. Because sex differences in both behavior and physiology are typically reduced in monogamous species, we initially predicted that male and female prairie voles would exhibit similar behavioral responses to corticosterone. However, our findings suggest an unanticipated sexual dimorphism in the physiological processes modulating social preferences. This dimorphic involvement of stress hormones in pair bonding provides a proximate mechanism for regulating social organization, while permitting males and females to adapt their reproductive strategies in response to environmental challenges.

Adrenalectomy↗
PubMed1996

Cellular immunity is not compromised by high serum corticosterone concentrations in prairie voles.

Glucocorticoids compromise immune function in glucocorticoid-sensitive species (e.g., mice), but these immunosuppressive effects may be reduced in glucocorticoid-resistant species. Prairie voles (microtus ochrogaster) have been characterized as glucocorticoid-resistant to their high circulating levels of corticosterone. Because glucocorticoid-sensitive species display suppressed lymphocyte proliferation in response to elevated blood glucocorticoid levels, proliferative values were hypothesized to be reduced in house mice (Mus musculus) compared with prairie voles. Prairie voles exhibited significantly higher splenocyte proliferative responses to the T cell mitogen, Concanavalin A, despite having higher basal total and free serum corticosterone levels than mice. Neither total nor free serum corticosterone correlated with proliferative responses from either species. These data provide further evidence for glucocorticoid resistance in prairie voles and suggest that the interactions between the hypothalamic-pituitary-adrenal axis and the immune system in prairie voles may differ from those in mice or other glucocorticoid-sensitive species. Therefore, prairie voles may serve as a valuable animal model for the syndrome of glucocorticoid resistance in humans and the role of glucocorticoids in conditions characterized by a hyperactive immune system.

Animals↗
PubMed1995

Adrenocorticoid hormones and the development and expression of mammalian monogamy.

Based on research with prairie voles, we hypothesize that the unusual patterns of reproduction and social behavior associated with mammalian monogamy may arise as a consequence of normal developmental exposure to high levels of glucocorticoids and/or other hormones of the HPA axis. Increased HPA activity could functionally inhibit some of the masculinizing processes expected during the perinatal period. We hypothesize that the unique behavioral, physiological, and anatomical changes associated with monogamy may reflect the adaptive consequences of reduced exposure to the masculinizing actions of HPG hormones, such as testosterone. Reproductively naive, unpaired adult prairie voles also show unusual patterns of adrenal activity, including a marked decline in corticosterone levels within minutes following exposure to novel animals of the opposite sex. In females, this decline in corticosterone may contribute to pair bonding, since corticosterone injections inhibit, and adrenalectomy is associated with a facilitation of pair bond formation. In males, corticosterone injections facilitate pair bonding and adrenalectomy has the opposite effect. In animals from established social pairs corticosterone levels also fluctuate according to the social environment of the animal; the absence of a familiar partner is associated with increased corticosterone secretion, and in the presence of the familiar partner corticosterone levels tend to decline. Prairie voles may offer a valuable source of information regarding the behavioral, anatomical, and physiological consequences of long-term and short-term exposure to high levels of adrenal activity in the absence of pathology.

Adrenal Cortex Hormones↗
PubMed1990

Social cues influence growth and sexual maturation of the male musk shrew (Suncus murinus).

Musk shrews were maintained from weaning (20 days of age) for 20 or 40 days in one of several social conditions. In Exp. 1, young males housed with adult females gained more weight and had heavier sex accessory organs than did young males housed with an adult male or reared alone. In Exp. 2 this same pattern of accelerated growth and sexual maturation was found when males were reared directly with an adult female or in a split cage where a wire barrier served to separate the male and his adult female cagemate. In Exp. 3, males were reared in cages containing clean or soiled bedding: soiled bedding was taken once every 5 days from the cage of an adult male, or a female. Under these conditions differences in the weights of reproductive tissues showed minimal variation with housing condition after 20 days of treatment. At that time males reared in soiled bedding taken from the cage of an adult female had accelerated development compared with control males. In Exp. 4, males were housed alone or in a split cage with an adult female which was separated by a wire mesh or a solid, opaque barrier. Males separated by a solid barrier from their female cagemates for 40 days had reproductive tissue weights equivalent to those measured in males reared alone. Taken together these results suggest that the presence of an adult female has dramatic effects on body growth and development of reproductive target tissues in young male musk shrews. Male-female social interactions could play an important role in the timing of puberty in this opportunistically breeding tropical mammal.

Androgens↗