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Variations in cellular sensitivity to glucocorticoids: observations and mechanisms
Monographs on Endocrinology
|January 1, 1979
Summary
Glucocorticoid sensitivity varies widely due to cellular programming and genetic factors, not just receptor differences. This impacts disease pathogenesis and drug resistance, particularly in lymphoid cells.
Area of Science:
- Endocrinology
- Cell Biology
- Genetics
Background:
- Glucocorticoids exert diverse effects across mammalian tissues despite a common receptor.
- Significant inter- and intra-tissue variations in glucocorticoid sensitivity exist.
- These variations influence cellular responses, including growth inhibition, cell killing, and immunological functions.
Purpose of the Study:
- To review the spectrum of physiological, pathological, and genetic variations in glucocorticoid sensitivity.
- To explore the mechanisms underlying divergent tissue responses to glucocorticoids.
- To investigate genetic alterations affecting glucocorticoid receptor function and cellular resistance.
Main Methods:
- Review of existing literature on glucocorticoid sensitivity.
- Analysis of lymphoid cell systems to understand sensitivity differences.
- Examination of genetic variations and mutant cell lines with altered glucocorticoid responses.
Main Results:
- Glucocorticoid response diversity is largely attributed to cellular programming beyond receptor variations.
- Sensitivity differences are observed in lymphoid cells, affecting cell killing and immune functions.
- Genetic mutations in glucocorticoid receptors lead to steroid resistance, with defects in receptor properties rather than just levels.
Conclusions:
- Cellular programming, not solely receptor differences, dictates glucocorticoid sensitivity.
- Variations in sensitivity can be influenced by developmental stages, aging, and other hormones.
- Understanding genetic variations in glucocorticoid sensitivity is crucial for disease pathogenesis and therapeutic strategies.