Estrogen inhibits tuberoinfundibular dopaminergic neurons but does not cause irreversible damage

MOREL GR; CARON RW; CONSOLE GM; SOAJE M; SOSA YE; RODRIGUEZ SS; JAHN GA; GOYA RG

BRAIN RESEARCH BULLETIN

PERGAMON-ELSEVIER SCIENCE LTD

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

0361-9230

Dopaminergic neurons of the hypothalamic tuberoinfundibular dopaminergic (TIDA) system exert a tonicinhibitory 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 whetherestrogen in high doses can cause permanent damage to TIDA function, we submitted young female ratsto continue high doses of estrogen administered, either centrally (intrahypothalamic estrogen implants)or peripherally (subcutaneous estrogen implants or weekly intramuscular (i.m.) injections for 7 weeks),subsequently withdrawing the steroid and observing the evolution of lactotrophes, serum PRL and TIDAneurons. Serum PRL was measured by radioimmunoassay whereas tyrosine hydroxylase positive (TH+)neurons and PRL cells were morphometrically assessed in sections of fixed hypothalami and pituitaries,respectively. After 30 days, hypothalamic estrogen implants induced a significant increase in serum PRL,whereas TH+ neurons were not detectable in the arcuate-periventricular hypothalamic (ARC) region ofestrogen-implanted rats. Removal of implants on day 30 restored TH expression in the ARC and broughtserum PRL back to basal levels 30 days after estrogen withdrawal. Subcutaneous or i.m. administrationof estrogen for 7 weeks induced a marked hyperprolactinemia. However, 30 weeks after estrogen withdrawal,TH neuron numbers in the ARC were back to normal and serum PRL returned to basal levels. Afterperipheral but not central estrogen withdrawal, pituitary weight and lactotrophic cell numbers remainedslightly increased. Our data suggest that estrogen even at high doses, does not cause permanent damageto TIDA neurons.© 2009 Elsevier Inc. All rights reserved