Terpenoids are a numerous class of natural compounds that possess various biological activities, including estrogenic action. In the present paper we report the results of study of estrogen and membrane activity of aromatic and aliphatic derivatives of sesquiterpen alcohol carotene, isolated from Ferula genus, directly testing the hypothesis that these compounds modulate hormone production via affecting the mobilization of intracellular calcium. We have found that the complex ethers of sesquiterpen with aromatic but not with aliphatic substituents, more than 3-time increased the weight of uterus of prepubertal rats and stimulated the appearance of estrus in ovariectomized female rats in 80-100% of injected animals. Experiment carried out on intact cells (thymocytes) using the Ca2+ indicator Fura-2/AM showed that terpenoids exhibited stimulatory effect on the pubescence of rats by the increase of [Ca2+]i. Furthermore, as observed in the experiments in vitro, these terpenoids dramatically inhibit Ca-ATPase and Na, K-ATPase of intracellular and plasma membranes and cause structural changes in membranes as was shown by EPR spectroscopy method. These data suggest that sesquiterpens could exert their estrogen-like activity via increase of intracellular Ca2+.
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