Gonadal Steroids Exert Facilitating and “Buffering ” Effects on Glucocorticoid-Mediated Transcriptional Regulation of Corticotropin-Releasing Hormone and Corticosteroid Receptor Genes in Rat Brain

Gonadal steroids profoundly influence several brain functions and are apparently responsible for gender-specific differences in the regulation of hypothalamic–pituitary–adrenal (HPA) secretions. In this study, we examined the so-called “activational” effects of gonadal steroids on the glucocorticoid-mediated regulation of the gene transcription of corticotropin-releasing hormone (CRH) and corticosteroid receptors in brain areas of relevance for the control of pituitary–adrenal secretion. The efficacy of adrenalectomy (ADX) and chronic treatment with high doses of corticosterone (B) to regulate the gene transcription of CRH and corticosteroid receptors in the hypothalamic paraventricular nucleus (PVN) and hippocampus was studied in male and female rats under the conditions of deprivation of gonadectomy (GDX) and replacement with different gonadal steroids, such as estradiol (E 2), progesterone (P), and dihydrotestosteron

Insidious adrenocortical insufficiency underlies neuroendocrine dysregulation in TIF-2 deficient mice.

International audienceThe transcription-intermediary-factor-2 (TIF-2) is a coactivator of the glucocorticoid receptor (GR), and its disruption would be expected to influence glucocorticoid-mediated control of the hypothalamo-pituitary-adrenal (HPA) axis. Here, we show that its targeted deletion in mice is associated with altered expression of several glucocorticoid-dependent components of HPA regulation (e.g., corticotropin-releasing hormone, vasopressin, ACTH, glucocorticoid receptors), suggestive of hyperactivity under basal conditions. At the same time, TIF-2(-/-) mice display significantly lower basal corticosterone levels and a sluggish and blunted initial secretory response to brief emotional and prolonged physical stress. Subsequent analysis revealed this discrepancy to result from pronounced aberrations in the structure and function of the adrenal gland, including the cytoarchitectural organization of the zona fasciculata and basal and stress-induced expression of key elements of steroid hormone synthesis, such as the steroidogenic acute regulatory (StAR) protein and 3beta-hydroxysteroid dehydrogenase (3beta-HSD). In addition, altered expression levels of two nuclear receptors, DAX-1 and steroidogenic factor 1 (SF-1), in the adrenal cortex strengthen the view that TIF-2 deletion disrupts adrenocortical development and steroid biosynthesis. Thus, hyperactivity of the hypothalamo-pituitary unit is ascribed to insidious adrenal insufficiency and impaired glucocorticoid feedback

A dynamic model of circadian rhythms in rodent tail skin temperature for comparison of drug effects

<p>Abstract</p> <p>Menopause-associated thermoregulatory dysfunction can lead to symptoms such as hot flushes severely impairing quality of life of affected women. Treatment effects are often assessed by the ovariectomized rat model providing time series of tail skin temperature measurements in which circadian rhythms are a fundamental ingredient. In this work, a new statistical strategy is presented for analyzing such stochastic-dynamic data with the aim of detecting successful drugs in hot flush treatment. The circadian component is represented by a nonlinear dynamical system which is defined by the van der Pol equation and provides well-interpretable model parameters. Results regarding the statistical evaluation of these parameters are presented.</p