Regulation of estrogen receptor messenger ribonucleic acid in rat hypothalamus by sex steroid hormones.
Sex steroid hormone receptors are thought to mediate the actions of their respective hormones by functioning as ligand-activated nuclear transcription factors that alter the expression of specific sets of hormone-responsive genes. Particularly high densities of estrogen receptor (ER)-containing neurons are located in the arcuate nucleus (ARH) and ventrolateral part of the ventromedial nucleus (VMHvl) of the hypothalamus, and these cell groups are thought to play key roles in the neuroendocrine control of reproductive function. Thus, hormonal regulation of ER gene expression in ARH and VMHvl neurons represents a direct mechanism by which circulating sex steroids could affect the responsiveness of these neurons to hormonal activation. We used in situ hybridization histochemistry to evaluate the influence of estradiol and testosterone on levels of ER mRNA within the ARH and VMHvl of adult male and female rats. In female rats, estradiol treatment reduced levels of ER mRNA in the ARH and VMHvl within 24 h relative to levels in both ovariectomized control animals and intact estrous females. Comparable results were obtained in male rats, except that testosterone did not significantly attenuate ER mRNA hybridization in the VMHvl until after 3 days of hormone treatment, and only a minor decrease was noted in the ARH, which was not statistically significant. In both male and female animals, the overall density of labeling found over individual cells in emulsion-dipped autoradiograms was consistently lower in hormone-treated animals compared with that over cells in gonadectomized controls, suggesting that the observed decreases in ER mRNA hybridization measured over the ARH and VMHvl are due to changes in cellular levels of ER mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Simerly
R B
RB
Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California 92037.
Young
B J
BJ
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology; D004971:Estrus; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000235:genetics*; D012680:Sensitivity and Specificity; D013739:Testosterone / Q000494:pharmacology; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*
D012739:Gonadal Steroid Hormones; D008024:Ligands; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013739:Testosterone; D004958:Estradiol