New Questions About Steroids

Recent studies on laboratory rodents demonstrate that steroid hormones can cause irreversible damage and dysfunction on select target cells in the adult brain. During the past 20 years, a careful distinction was proposed between the short‐ and long‐term effects of hormones on the rodent brain. The permanent (organizing) actions of sex steroids on the brain were considered restricted to development and completed by puberty. Thereafter, sex steroids continue to have crucial roles in reproductive physiology and behavior, but the effects were widely considered to be short‐term, lasting weeks or a few months at most. However, a number of researchers have clearly shown that sustained high physiologic levels of steroids have long lasting effects on the adult rodent brain. A portentious example is that prolonged stress with elevated corticosteroids kills specific neurons in the hippocampus if maintained for three months in young rats. 1 These same neurons are also commonly lost during aging in rodents and humans. Similar steroid‐dependent mechanisms may be involved in the neuroendocrine changes in aging female rodents that include lactotrophic pituitary tumors and impaired control of prolactin and luteinizing hormone. These same changes are greatly reduced during aging by ovariectomy of rodents when young and, moreover, can be prematurely induced in the young by extended treatments with estrogens. 2 The concept that endogenous steroids interact with aging processes is also supported by considerable data showing that hypophysectomy retards many aspects of aging in peripheral cells of rodents. 2