Growth hormone is produced within the hippocampus where it responds to age, sex, and stress

doi:10.1073/pnas.0507776103

Growth hormone is produced within the hippocampus where it responds to age, sex, and stress

*Department of Neurology and Center for Neurologic Disease, Harvard Medical School, Boston, MA 02115;
^†Neuroscience Research Institute, University of California, Santa Barbara, CA 93106; and
^‡Department of Psychology and Center for Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854

Edited by Bruce S. McEwen, The Rockefeller University, New York, NY, and approved February 27, 2006 (received for review September 6, 2005)

Abstract

Recent studies by our group and others have demonstrated that growth hormone (GH) is produced endogenously within the hippocampal formation, a brain structure associated with learning and aspects of emotional experience. Here, we demonstrate that this endogenously produced GH is modulated by age and sex differences and the presence of estrogen. GH mRNA levels were higher in females than males, especially during proestrus, a stage of estrus when estrogen levels are elevated. Moreover, GH expression was increased in ovariectomized females that were treated with estradiol. This increase in GH mRNA in response to estrogen was followed by the appearance of GH protein and was negatively correlated with the expression levels of insulin-like growth factor-I mRNA, suggesting a feedback relationship between insulin-like growth factor-I and GH in the brain. GH mRNA levels were also elevated in primary neuronal cultures exposed to 17-β-estradiol in vitro, further confirming the direct influence of estrogen on GH expression. Finally, exposure to an acute stressful event increased the expression and production of GH in both males and females. However, the stress-induced increase of GH in females depended on the stage of the estrous cycle in which they were exposed to the stressful event. Together, these data further demonstrate that GH is endogenously produced in the adult hippocampal formation, where it is regulated by age, estrogen, and exposure to environmental stimuli. These results suggest that GH may be involved in functions ascribed to the hippocampus, such as learning and the response to stressful experience.

Footnotes

^§To whom correspondence should be addressed. E-mail: shors{at}rutgers.edu
Author contributions: C.P.D., K.S.K., and T.J.S. designed research; C.P.D. and T.J.S. performed research; C.P.D., K.S.K., and T.J.S. contributed new reagents/analytic tools; C.P.D. and T.J.S. analyzed data; and C.P.D. and T.J.S. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

Abbreviations:

GH,

growth hormone;

GHR,

GH receptor;

IGF,

insulin-like growth factor;

OVX,

ovariectomy.
Freely available online through the PNAS open access option.