Growth Hormone Is Produced within the Hippocampus Where It Responds to Age, Sex, and Stress

• Published in: Proceedings of the National Academy of Sciences - PNAS 2006-04, Vol.103 (15), p.6031-6036
• Main Authors: Donahue, Christine P., Kosik, Kenneth S., Shors, Tracey J.
• Format: Article
• Language: English
• Subjects: Age differences; Aging - physiology; Animals; Behavioral neuroscience; Biological Sciences; Brain; Diestrus; DNA Primers; Estrogens; Estrus; Female; Female animals; Gender differences; Growth Hormone - genetics; Growth hormones; Hippocampus; Hippocampus - growth & development; Hippocampus - physiology; Hippocampus - physiopathology; Insulin-Like Growth Factor I - genetics; Learning; Learning - physiology; Male; Male animals; Mating behavior; Messenger RNA; Neurosciences; Polymerase Chain Reaction; Proestrus; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; Sex Characteristics; Stress; Stress, Psychological
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0507776103

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.