Estrogen inhibits tuberoinfundibular dopaminergic neurons but does not cause irreversible damage.

MOREL G.L.; CARON R.W.; CONSOLE G.; SOAJE M.; SOSA E.; RODRIGUEZ S.S.; JAHN G.A.; GOYA R.G.

BRAIN RESEARCH BULLETIN

Elsevier Science Inc.,

Lugar: New York; Año: 2009 vol. 80 p. 347 - 352

0361-9230

Dopaminergic neurons of the hypothalamic tuberoinfundibular (TIDA) system exert a tonic inhibitory control on prolactin (PRL) secretion whereas estrogen, known to inhibit TIDA neuron function, has been postulated to be toxic to TIDA neurons when it is chronically high. In order to determine whether estrogen in high doses can cause permanent damage to TIDA function, we submitted young female rats to continued high doses of estrogen administered, either centrally (intrahypothalamic estrogen implants) or peripherally (subcutaneous estrogen implants or weekly i.m. injections of estrogen) for several weeks, subsequently withdrawing the steroid and observing the evolution of serum PRL, pituitary weight and the TIDA neuron population. Serum PRL was measured by radioimmunoassay whereas tyrosine hydroxylase (TH) expression was immunohistochemically assessed in coronal sections of fixed hypothalami. After 30 days, hypothalamic estrogen implants induced a significant increase in serum PRL (Experimental versus controls, 150±40 vs. 24± 3 ng/ml), whereas TH+ neurons were not detectable in the arcuate-periventricular hypothalamic (ARC) region of estrogen-implanted rats. Removal of implants on day 30 restored TH expression in the ARC and brought serum PRL back to basal levels 30 days after estrogen withdrawal. Subcutaneous or i.m. administration of estrogen for 7 weeks induced a marked hyperprolactinemia (>500 ng/ml). However, 20 weeks after estrogen withdrawal, TH expression in the ARC was normal and serum PRL returned to basal levels. After peripheral but not central estrogen withdrawal, pituitary weight remained significantly increased. Our data suggest that estrogen even at high doses, does not cause permanent damage to TIDA neurons.