Possible mechanism of action of 2-hydroxylated estradiol on the positive feedback control for LH release in the rat

Abstract

Evidence was given to support a positive role of 2-hydroxyestradiol on the LH surge. The catecholestrogen may act by its catechol A ring on the nucleus arcuatus COMT, consequently leaving the noradrenaline free. The result may be a longer action on the peptidergic terminal in the median eminence and an increase in the LH secretion by the pituitary. This assumption is supported by the observations that the catecholestrogen effect can be mimicked by homocystein, an aminoacid able also to inhibit COMT activity, having neither a steroid nor a catechol structure. The fact that alpha-MIT is able to prevent homocystein-induced increase in LH suggests that it is acting by protecting the local increase of the catecholamine. After ten years of intensive effort to understand the possible physiological role of the catecholestrogens, attention was mostly paid to its structural similarity to estrogen and a great deal of effort was made to understand its function by acting upon the estrogen receptor in the cytosol. The evidence for catecholestrogen action upon COMT, an outside membrane enzyme involved in the process of catecholamine degradation, supports the idea of a catechol action for 2-OHE2. The present evidence strongly supports the physiological importance of the catechol group in the 2-OHE2 in its action mechanism. However, a true physiological role for the catecholestrogens remains to be solved. The evidence we bring confirms once more that catecholestrogens may have a function and explains a new mechanism of action. However, the basic question concerning the true amount of catecholestrogen existing in the hypothalamic nuclei, either brought by the blood stream or locally produced, still needs to be solved: we cannot say whether the mechanism we described is a functioning one, whether it is just brought about by the experimental increase of the catecholestrogen or the artificial blockage of COMT.