Oestrogen Uptake by the Central Nervous System
Authors: Rosner J.M. , Denari J.H. , Castro-Vázquez A. , Nagle C.A. , Neuspiller N.R. , de P. Bedés Greta D. , Pedroza E. , Martin J.L. , Gómez Elena 
Published: March 2010

This presentation covers three areas in relation with the mechanism of oestrogen action on the central nervous system. The ability of the uterus, vagina, anterior pituitary and anterior hypophysis to take up and retain oestradiol has been proposed as a distinctive character for the oestrogenic target organs. Although no specific protein receptors have been isolated in the neocortex, the administration of oestradiol was able to increase the incorporation of cytidine to RNA, and the protein synthesis. Those findings, together with the fact that oestradiol is concentrated and retained in the nuclei of the cerebral cortex, forced us to review the concept of target organs. The presence of very small quantities of oestradiol in the central nervous system cell nuclei may reflect the amounts that the tissue requires, and the emphasis that has always been put on quantity should be placed on there-sholds for oestrogen action in different tissues. The capacity of progestagens to compete with oestradiol binding was evaluated by organotypic culture of the hypothalamus. In a group of experiments, progestagens were added before oestradiol and, in the other group, both progestagens and oestradiol were added simultaneously to the medium. Oestradiol binding was significantly inhibited when either of the progestagens derived from 17&#913;-hydroxyprogesterone (chlormadinone acetate (CA) and medroxyprogesterone acetate (MPA) was added simultaneously. When added previously to oestradiol, progestagens behaved differently. MPA diminished the oestradiol binding significantly; CA, on the contrary, increased it. RO4–8347, a compound derived from retroprogesterone, diminished the oestradiol binding when added previously, but not when added simultaneously. Lynestrenol and norgestrel, both 19-norsteroids, inhibited the oestradiol binding when added simultaneously, but not when added previously. Catecholamines and oestrogens participate in the control of ovulation and it was thought worthwhile to investigate their relationships in the hypothalamus and the uterus. The simultaneous administration of epinephrine and labelled 17&#914;-oestradiol injected i.p. produced a significant increase in the uptake of oestradiol by the anterior hypothalamus and a diminution in the uterus. When norepinephrine and 17&#914;-oestradiol were simultaneously injected, the uptake of oestradiol was increased in the uterus and not modified in the hypothalamus. As the concentration of histamine is higher in the hypothalamus than in any brain region, it seemed interesting to us to study the effect of histamine on the uptake of oestradiol and testosterone. Histamine increased the uptake of labelled oestradiol by the uterus and the hypothalamus. When histamine effects were studied in relation with testosterone uptake, it increased the hypothalamic, but not the uterine uptake. Even knowing that the mammalian pineal gland has an inhibitory effect on gonadal function, little attention has been paid to the role of gonadal hormones on pineal activity. In view of the contradictory results concerning the action of oestradiol on the pineal gland, we have studied in our laboratory the uptake of labelled oestradiol by this gland and the hydroxyindole-O-methyl transferase (HIOMT) modifications produced by oestradiol and/or norepinephrine administration. Our results demonstrate that the pineal ability to take up oestradiol was significantly higher than that of the uterus. Besides, the administration of oestradiol to spayed female rats inhibited the pineal HIOMT activity, this effect being reversed by norepinephrine, which when injected alone modifies neither the uptake of oestradiol nor HIOMT activity.