Steroid resistance in the squirrel monkey: an old subject revisited.

I t has been more than 30 yr since Brown et al. (1968) reported at the 52nd Annual FASEB Meeting in Atlantic City that squirrel monkeys have high circulating levels of the adrenal steroid cortisol compared with humans. This work was subsequently published in full (Brown et al. 1970) and confirmed by other laboratories (for example, Chrousos et al. 1982; Coe et al. 1978; Klosterman et al. 1986; Manogue et al. 1975). In the meantime, it was recognized that other steroid hormones, including progesterone, 17|3-estradiol, and testosterone, are also elevated in squirrel monkeys (Mendoza et al. 1978; Wilson et al. 1978; Wolf et al. 1977). Since these discoveries, a number of reports have contributed to our understanding of these phenomena, although not until recently have we begun to appreciate the molecular changes that led to these elevated hormone levels. The goal of this article is not to review our current knowledge of secretion and metabolism of each of these steroids in the squirrel monkey. Such review has been expertly achieved in chapters published in a volume of Advances in Experimental Medicine and Biology dedicated to the late Dr. Mortimer Lipsett (Chrousos et al. 1986a,b; Siiteri 1986). Rather, this article details recent findings that have provided insight into the molecular events that led to hypercortisolemia, briefly describing their relevance to the secretion of other steroid hormones in squirrel monkeys. The issue of elevated steroid hormone levels is important to laboratory animal science for several reasons. First, it should be appreciated that high circulating levels of some steroid hormones are a normal finding in captive squirrel monkeys. Second, it is generally agreed that this phenomenon has occurred as a normal physiological response to a state of hormone insensitivity or resistance in responsive tissues, including tissues such as the hypothalamus and pituitary gland, which mediate the feedback response. As a consequence, hormone levels are high to compensate for endorgan resistance, and squirrel monkeys enjoy a relatively normal pituitary-adrenal physiology albeit at a higher hormonal set-point. Thus, cortisol secretion in squirrel monkeys is appropriately stimulated by chair restraint (Brown et al. 1970) and social and environmental perturbations (Coe et