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A Peiffer

Publications and source records attributed to A Peiffer.

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Antidepressant and other centrally acting drugs regulate glucocorticoid receptor messenger RNA levels in rat brain.

The effect of imipramine, desipramine, ketanserin and lithium on Type II glucocorticoid receptor (GR) mRNA levels was studied in rat brain regions involved in the control of the hypothalamo-pituitary-adrenal (HPA) axis, the dysregulation of which has been implicated in the pathophysiology of major depression. Northern blot analysis of Type II GR mRNA showed that treatment of male rats with either desipramine or imipramine increased hypothalamic and hippocampal GR mRNA levels. Upregulation of GR mRNA following administration of imipramine was found in brain regions of female rats, while desipramine had no effect. Ketanserin increased levels of GR mRNA in hippocampus of male, but not female, rats. Lithium also was able to induce important increases rat brain GR mRNA; this effect was particularly marked in females. We conclude that desipramine, imipramine, ketanserin and lithium can modulate GR mRNA in regions of rat brain involved in the control of the HPA axis and may have a common mechanism of action at the level of the GR gene. Sexual dimorphism for drug regulation of brain GR mRNA content was shown and may be related to sex differences in the prevalence of certain affective disorders.

Amygdala

Hormonal regulation of type II glucocorticoid receptor messenger ribonucleic acid in rat brain.

Differences in the regulation of type II glucocorticoid receptor (GR) mRNA levels in female rat brain regions involved in the control of the hypothalamic-pituitary-adrenal axis were studied by Northern blot analysis after chronic administration of corticosterone or dexamethasone to adrenalectomized (ADX), ovariectomized (OVX), and ADX/OVX animals. The effect of chronic estradiol or progesterone treatment of intact animals was also studied. Our results show that type II GR mRNA levels of ADX animals were significantly increased above control values in amygdala (140%) and hippocampus (196%), but not in hypothalamus. These increased transcript levels were down-regulated by corticosterone or dexamethasone, with the exception of those in the amygdala, where corticosterone had no effect. Ovariectomy significantly increased hypothalamic GR mRNA content (174%) over control values, and this increase was sensitive to dexamethasone. The combined effect of adrenalectomy/ovariectomy on GR mRNA levels was greater than that of adrenalectomy only in amygdala. Corticosterone increased amygdala transcript levels in OVX and ADX/OVX animals. Estradiol administration to intact animals raised the GR mRNA content of amygdala, while progesterone treatment had no effect on any of the brain regions studied. We conclude that there exists heterogeneity with respect to type II GR mRNA regulation by corticosterone and dexamethasone in brain regions of ADX female rats, and that certain limbic structures show greater sensitivity to these hormonal manipulations, suggesting a more prominent role in the regulation of the hypothalamic-pituitary-adrenal axis. Our results also suggest that circulating estrogens can influence the sensitivity of brain structures (i.e. hypothalamus and amygdala) to glucocorticoids by altering GR mRNA levels. These regions may represent integration sites at which gonadal steroids are able to alter stress hormone secretion.

Adrenalectomy

[Mandibular reconstruction using a pedicled osteomyocutaneous flap of the latissimus dorsi].

The authors report their experience with reconstruction of loss of mandibular substance due to wide or complicated resections for cancer. A series of 8 reconstructions using a latissimus dorsi osteo-myocutaneous pediculated flap and the 10th rib helped to define the advantages and disadvantages of this form of complex flap. Since a latissimus dorsi pediculated flap has classically been used in maxillo-facial reconstruction, an osteo-myocutaneous flap, including a portion of the 10th rib, is naturally appropriate for the reconstruction of a major loss of substance involving the mandible and related structures. The separation technique and trans-cervical transposition are described. The advantages of this form of flap are the ease with which it may be detached and the reliability of the vascular pedicle. The principal disadvantages are the relatively large volume, the difficulty in dissociating the cutaneous layer from the bony layer and the difficulties involved in the fixation of the bone graft to a prosthetic plate. Problems with rehabilitation are also discussed.

Bone Transplantation

Estrogen-induced decrease of glucocorticoid receptor messenger ribonucleic acid concentration in rat anterior pituitary gland.

Using Northern blots and hybridization techniques, we have identified an approximately 6.5 kilobase glucocorticoid receptor mRNA species in rat anterior pituitary gland. Ovariectomy resulted in an approximately 2-fold increase in glucocorticoid receptor mRNA concentrations. This effect was maximal 8 days after surgery and glucocorticoid receptor mRNA levels remained elevated for at least up to 4 weeks. Administration of 17-beta-estradiol completely reversed the ovariectomy-induced increase in glucocorticoid receptor mRNA content of pituitary gland. Treatment of rats with corticosterone did not influence the ovariectomy-induced increase in glucocorticoid receptor mRNA content, indicating that this increase is not mediated via effects on circulating glucocorticoid levels or availability. In situ hybridization experiments confirmed the ovariectomy-induced increase in glucocorticoid receptor mRNA content and indicated that this action is widely distributed throughout the anterior pituitary gland.

Adrenalectomy

Age-related changes in glucocorticoid receptor binding and mRNA levels in the rat brain and pituitary.

Hypothalamic-pituitary-adrenal (HPA) activity under both basal and poststress conditions is often increased in the aged rat. This change has been associated with the loss of corticosteroid receptors in specific regions that mediate glucocorticoid negative feedback. In order to study the cellular basis for the loss of receptors, we measured glucocorticoid (type II corticosteroid) receptor binding and mRNA levels in pituitary and selected brain regions in rats at 6, 12, and 24 months of age. Receptor binding, measured using [3H]RU 28362, was stable in all regions (pituitary, hypothalamus, amygdala, and frontal cortex) except the hippocampus, where there was about a 40% decrease in binding capacity, with no change in the affinity of the receptor for RU 28362. The loss of receptors in the hippocampus was apparent in animals at 12 months of age, and binding was further decreased at 24 months. Glucocorticoid receptor mRNA levels were significantly higher in all regions at 12 months of age than at 6 months. By 24 months, however, receptor mRNA levels in most regions had returned to levels that were similar to those at 6 months of age. In contrast, glucocorticoid receptor mRNA levels in the hippocampus were significantly decreased at 24 months of age compared to levels at both 6 and 12 months of age. Thus, in general, variations in receptor mRNA levels parallel those in receptor binding in animals 6 and 24 months of age, with the hippocampus as the only region showing a significant loss of receptors and a decrease in mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging