QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 5, 2009, 29(31):9714-9718; doi:10.1523/JNEUROSCI.0135-09.2009

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Waters, E. M. Articles by Simerly, R. B. PubMed PubMed Citation Articles by Waters, E. M. Articles by Simerly, R. B.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Estrogen Induces Caspase-Dependent Cell Death during Hypothalamic Development

Elizabeth M. Waters^1,2 and Richard B. Simerly³

¹Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10065, ²Oregon National Primate Research Center, Oregon Health & Sciences University, Beaverton, Oregon 97006, and ³Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California 90027

Correspondence should be addressed to Dr. Elizabeth M. Waters, Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065. Email: e.waters{at}rockefeller.edu

The sexually dimorphic population of dopamine neurons in the anteroventral periventricular nucleus of the preoptic region of the hypothalamus (AVPV) develops postnatally under the influence of testosterone, which is aromatized to estrogen. There are fewer dopaminergic neurons labeled with tyrosine hydroxylase (TH) in the male AVPV than the female, and sex steroids determine this sex difference, yet the role of cell death in specifying numbers of dopaminergic neurons in the AVPV is unknown. Estradiol treatment of the AVPV, in vivo and in vitro, was used to manipulate TH-ir cell number. In vitro, concurrent treatment with the estrogen receptor antagonist ICI 182,780 rescued TH-ir cells. Cyclosporin A, an inhibitor of cell death dependent on the opening of a mitochondrial permeability transition pore also blocked TH-ir cell loss. In vivo, estradiol increased the number of apoptotic profiles, both TUNEL and Hoechst labeled nuclei, in the AVPV. This increased apoptosis was also dependent on the presence of the form of the estrogen receptor. To test for caspase dependent TH-ir cell loss, the pancaspase inhibitor ZVAD (N-benzyloxycabonyl-Val-Ala-Asp-fluoromethylketone) was used to rescue TH-ir cells from estradiol-mediated reduction in number. Together, these data suggest that an intrinsic cell death pathway is activated by estrogen to regulate TH-ir cell number. Thus, in contrast to the more widespread neuroprotective actions of sex steroids in the mammalian nervous system, in the AVPV estrogen regulates dopaminergic neuron number through a caspase-dependent mechanism of apoptotic cell death.

---

Received Jan. 9, 2009; revised April 30, 2009; accepted May 25, 2009.

Correspondence should be addressed to Dr. Elizabeth M. Waters, Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065. Email: e.waters{at}rockefeller.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help