2-Hydroxyestradiol is not mediating the effects of estradiol on tuberoinfundibular dopaminergic neurons controlling prolactin secretion in female rats.

Conversion of estrogens in their hydroxylated derivatives has been proposed as one of the mechanisms of action for these steroids in the brain. However, the actions of catechol estrogens on the hypothalamic control of the prolactin (PRL) release seem to be different to the effects caused by native estrogens. To clarify this question, we have examined the activity of tuberoinfundibular dopaminergic (TIDA) neurons in ovariectomized rats treated with estradiol (E2) or 2-hydroxyestradiol (OHE2), both administered alone or previously to progesterone (P). L-3,4 dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) ratio in the medio basal hypothalamus (MBH), the anterior pituitary (AP) content of DA and the PRL release into the peripheral blood have been used as indexes of neural activity of TIDA system. Ovariectomy caused a significant reduction in plasma PRL levels, with increases of the DOPAC/DA ratio in MBH and of the AP content of DA. These changes were reversed by administration of E2, suggesting that this steroid exerted its stimulatory effect on PRL release by decreasing the activity of TIDA neurons. In contrast, OHE2 was unable to alter plasma PRL levels, the DOPAC/DA ratio in the MBH and the AP content of DA. On the other hand, P was able to stimulate the PRL release, but it needed a previous priming action of E2 since it was unable to modify plasma PRL levels when it was injected alone. This priming effect of E2 for the P action was not exerted by OHE2. Hence, we can conclude that the conversion of E2 in its 2-hydroxylated derivative is not mediating the effects of this steroid, nor its priming action for the P effect, on the hypothalamic dopaminergic control of the PRL release.