Effects of steroids

USP (Megace) testolactone USP [968-93 ] C19H24O3 300.40 (61) or endrome-trium breast cancer hyper-calcemia common side effects of steroids fluid retention ... 

Teslac) formestane [566 8-3] C19H24O3 302.41 (62) iavestigational dmg hyper-calcemia common side effects of steroids... 

Asthma is a chronic inflammatory disease. Therefore steroids represent the most important and most frequently used medication. Already after the fust treatment, steroids reduce cellular infiltration, inflammation, and the LAR, whereas changes in the EAR require prolonged treatment to lower the existent IgE levels. The mechanisms of steroid actions are complex and only incompletely understood. Besides their general antiinflammatory properties (see chapter glucocorticoids), the reduction of IL-4 and IL-5 production from T-lymphocytes is particularly important for asthma therapy. The introduction of inhaled steroids, which have dramatically limited side effects of steroids, is considered one of the most important advancements in asthma therapy. Inhaled steroids (beclomethasone, budesonide, fluticasone, triamcinolone, momethasone) are used in mild, moderate, and partially also in severe asthma oral steroids are used only in severe asthma and the treatment of status asthmaticus. Minor side effects of most inhaled steroids are hoarseness and candidasis, which are avoided by the prodrug steroid ciclesonide. 

Another type of NR crosstalk, which has only recently been recognized, is the so-called nongenomic actions of several receptors that induce very rapid cellular effects. Effectively, evidence has accumulated over several decades that steroid receptors may have a role that does not require their transcriptional activation, such as modifying the activity of enzymes and ion channels. While the effects of steroids that are mediated by the modulation of gene expression do occur with a time lag of hours, steroids can induce an increase in several second messengers such as inositol triphosphate, cAMP, Ca2+, and the activation of MARK and PI3 kinase within seconds or minutes. Many mechanistic details of these nongenomic phenomena remain poorly understood. Notably, controversy still exists as to the identity of the receptors that initiate the non-genomic steroid actions. However, it now appears that at least some of the reported effects can be attributed to the same steroid receptors that are known as NRs. 

Hou, Y.Y., Snzuki, Y, and Aida, K. (1999). Effects of steroid hormones on immnnoglobulin M (IgM) in rainbow trout, Oncorhynchus mykiss. Eish Physiology and Biochemistry 20, 155-162. 

Thorpe, K.L., Cummings, R.I., and Hutchinson, T. et al. (2003). Relative potencies and combination effects of steroidal estrogens in fish. Environmental Science and Technology 37, 1142-1149. 

Belehradek, J., Jr., Garrigos, M., Effects of steroids and verapamil on P-glycoprotein ATPase activity progesterone, desoxycorticosterone, corticosterone and verapamil are mutually non-exclusive modulators, Biochem. J. 1996, 337, 515-522. 

The answer is c. (Hardman, p 666.) Inhalation therapy minimizes systemic effects of steroids. Of the agents above, beclomethasone is the only one delivered by mete red-dose inhaler (MDl). 

It will be seen below that, in addition to genomic actions, there are nongenomic effects of steroids that modulate neurotransmitter release as well as ion traffic across the cell membrane, and do so frequently in coordination with genomic actions. 

Sarkar DK, Fink G (1980) Luteinizing hormone releasing factor in pituitary stalk plasma from long-term ovariectomized rats effects of steroids. J Endocrinol 86 511— 524... 

Gottardis MM, Ricchio ME, Satyaswaroop PG, Jordan VC (1990) Effect of steroidal and nonsteroidal antiestrogens on the growth of a tamoxifen-stimulated human endometrial carcinoma (EnCalOl) in athymic mice. Cancer Res 50 3189-3192... 

Jacob, S., Hayreh, D. J. S. and McClintock, M. K. (2001b) Context-dependent effects of steroid chemosignals on human physiology and mood. Physiol. Behav. 74, 15-27. 

Jacob, S. and McClintock, M.K. (2000) Psychological state and mood effects of steroidal chemosignals in women and men. Horm. Behav. 37, 57-78. 

Among these factors, social organizations, including inter- and intrasexual relationships, provide a matrix within which other behaviors occur. The behavioral effects of steroid hormones, especially in humans, have for the most part not been considered in these contexts. 

Lavie, Y., Harel-Orbital, T., Gaffield, W. and Liscovitch, M. (2001). Inhibitory effect of steroidal alkaloids on drug transport and multidrug resistance in human breast cancer cells. Anticancer Res., 21, 1189-1194. 

Lipophilic hormones, which include steroid hormones, iodothyronines, and retinoic acid, are relatively small molecules (300-800 Da) that are poorly soluble in aqueous media. With the exception of the iodothyronines, they are not stored by hormone-forming cells, but are released immediately after being synthesized. During transport in the blood, they are bound to specific carriers. Via intracellular receptors, they mainly act on transcription (see p. 358). Other effects of steroid hormones—e.g., on the immune system—are not based on transcriptional control. Their details have not yet been explained. 

Lipophilic signaling substances include the steroid hormones, calcitriol, the iodothy-ronines (T3 and T4), and retinoic acid. These hormones mainly act in the nucleus of the target cells, where they regulate gene transcription in collaboration with their receptors and with the support of additional proteins (known as coactivators and mediators see p.244). There are several effects of steroid hormones that are not mediated by transcription control. These alternative pathways for steroid effects have not yet been fully explained. 

Receptors for lipophilic hormones mediate the effects of steroid hormones and related signaling substances. They regulate the transcription of specific genes (see p. 378). The products of several oncogenes (e.g., erbA) belong to this superfamily of ligand-controlled transcription factors. 

Ligand-Independent Activation of Steroid Hormone Receptors and Non-genomic Effects of Steroids... 

IV.a.1.10. Immunosuppression. An important effect of steroid therapy is immunosuppression and this may be an essential part of their anti-inflammatory action in some situations. However patients may therefore be at risk of serious illness as a result of normally minor infection. This is particularly important with diseases such as chickenpox and measles. In addition the usual clinical effects of such diseases may be masked, delaying their diagnosis. 

Glucocorticoids are cautiously employed in various disease states, such as rheumatoid arthritis, although they still should be regarded as adjunctive rather than primary treatment in the overall management scheme. The toxic effects of steroids are severe enough that a number of factors must be considered when their prolonged use is contemplated. 

Steroids are important components in the treatment of hematopoietic malignancies. Their efficacy in chronic lymphocyfic leukemia and mulfiple myeloma sfems from fheir lympholyfic effecfs fo reduce cell prolifera-fion, promofe cell cycle arresf, and induce cell deafh by apopfosis. A complicafion of chronic lymphocyfic leukemia, fhaf is, aufoimmune hemolyfic anemia, also responds favorably fo steroids. However, the development of resistance may limit the effectiveness of steroid therapy. 

McEntee WJ, Mair RG Memory enhancement in Korsoff s psychosis with clonidine further evidence for a noradrenergic deficit. Ann Neurol 7 466-470, 1980 McEwen BS Non-genomic and genomic effects of steroids on neural activity. Trends Pharmacol Sci 12 141-147, 1991... 

Table 3. Contributions of the Allylic Axial 6/7-Substituents to the n-7r and n-n Cotton Effects of Steroidal 4-En-3-ones51 H3C...

Two other, faster-acting mechanisms produce some of the effects of steroids. Progesterone triggers a rapid drop in [cAMP], mediated by a plasma membrane receptor, and binding of progesterone to the classic soluble steroid receptor activates a MAPK cascade. 

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