PubMed · 1408560
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R A Jones, A M Grant. 1992. The "dose" question.. https://pubmed.ncbi.nlm.nih.gov/1408560/
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Recently, a significant seasonal variation in postdexamethasone (post-DST) cortisol values in depressed patients has been reported. This study aimed to investigate seasonal variation in post-DST cortisol values in 269 depressed patients admitted to a psychiatric ward during 70 consecutive months. By means of analysis of variance no significant differences could be detected in post-DST values in depressed men or women, alone or together, between the 12 months, the period November-February versus March-October, or between the tour quartiles. By means of spectral analysis no significant seasonal rhythms, i.e. annual or harmonic rhythms, could be found in the time series of post-DST cortisol values either in the total group of depressed patients or in depressed women separately (n = 190). Spectral analysis showed a significantly biannual rhythm in the post-DST cortisol values in depressed men, with peaks in June and December and troughs in March and September. This biannual rhythm explained 12.4% of the variance in the post-DST cortisol values of depressed men. The results show that there is a significant seasonal variation in post-DST cortisol values in depressed men, but not in depressed women.
Dexamethasone treatment of neonates to facilitate weaning from mechanical ventilation has become increasingly common. Despite thousands of infants being treated, most studies fail to demonstrate an improvement in long-term pulmonary and neurodevelopmental outcome. Much controversy remains regarding who should be treated, when treatment should begin, what the proper dose is, how long treatment should continue, and how adverse effects can be minimized. Early treatment prior to the onset of significant pulmonary inflammation may be an approach that improves outcomes and allows for shorter treatment courses. Risk assessment tools using ventilator requirements, adrenal function, or markers of pulmonary inflammation may allow for improved patient selection. Future studies will need to include a large number of subjects and will need to be continued beyond the neonatal period to assess long-term pulmonary and neurodevelopmental outcome.
Estrogens and glucocorticoids often act in opposition to regulate physiological responses. We investigated whether this might reflect the opposing actions of hormone-bound receptors on target genes regulated by the AP-1 response element. We performed a series of transfection experiments in which transcriptional activation, mediated by the AP-1 response element, was reflected in reporter gene activity. As previously described, we found that estrogens stimulate, whereas the glucocorticoid dexamethasone (Dex) inhibits, transcription through a model promoter from the collagenase gene (-73 to +63). This promoter bears a consensus AP-1 response element. When HeLa cells were treated with both estradiol and Dex, the steroids counteracted each other's transcriptional effects. The amount of transfected estrogen and glucocorticoid receptors (ER and GR) determined the extent to which Dex blunted estrogen stimulation or estrogen prevented Dex inhibition. The ER/GR interaction was observed both in the presence of estradiol and tamoxifen, which has previously been shown to have estrogen-like action at an AP-1 response element. The AP-1 family member c-Jun enhanced Dex inhibition and estradiol stimulation of transcriptional activation. c-Fos potentiated the effect of cotransfected c-Jun on estradiol stimulation but not Dex inhibition. The pattern of steroid responses was retained in the presence of the c-Jun activator phorbol 12-myristate 13-acetate. However, estradiol stimulation was lost in the presence of the c-Jun activator tumor necrosis factor-alpha. The ER/GR/AP-1 response element interaction was present, not only in a cell line originally derived from a uterine cervical adenocarcinoma (HeLa), but also in a cell line derived from the hypothalamus (GT1-1). Lastly, both progesterone receptor types A and B also interacted with the ER at the AP-1 site. These data indicate that opposing steroid influences can be mediated at the level of transcription through the AP-1 site and suggest that the integration of hormone action at this response element may underlie some of the opposing actions of estrogens and glucocorticoids or progestins on physiological responses.