What are ago-antagonistic couples? Their role in normal and pathological situations. Therapeutical consequences.
Two classes of steroid hormones are successively produced following a microbial infection stress in rat and man. First there are those of attenuation and acceptation, the glucocorticoids and progestins, which correspond to the temporization phase of reaction to stress. Secondly, there are those of rejection or creative reinforcement, namely the adrenal androgens converted in certain circumstances to estrogens by aromatization, which are necessary to fight against or accept the stressor. We suggest that these two classes of signal carrier molecules function as agonistic-antagonistic couples which work to prevent the organism from going too far in the direction of attenuation-acceptation or, on the contrary, in the direction of rejection-reinforcement. The presence of agonistic-antagonistic couples can be identified as regulating numerous other steps in the signal networks. Dysfunctions of such couples result in pathological situations, characterized by an imbalance in the concentration and correspondingly in the biological activity of one of the partners due to a change in the 'equilibrium constant' of the ago-antagonistic couple, changes in the level of synthesis or catabolism of one of the partners, the presence in adequate time and location of the partners, or the deficiency of the receptor of at least one of the partners. Different 'paradoxical' therapeutical strategies are envisaged to reequilibrate the imbalance.
Nunez
E A
EA
Faculté de Médecine, Hôpital X. Bichat (Université Denis Diderot), Laboratoire de Biochimie Endocrinienne, Paris, France.
Christeff
N
N
D000818:Animals; D005938:Glucocorticoids / Q000096:biosynthesis / Q000502:physiology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011372:Progestins / Q000096:biosynthesis / Q000502:physiology* / Q000627:therapeutic use*; D051381:Rats; D013312:Stress, Physiological / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*
D005938:Glucocorticoids; D011372:Progestins