Steinetz B G, Randolph C, Werner R, Mahoney C J
New York University Medical Center, Laboratory for Experimental Medicine and Surgery in Primates, Tuxedo 10987, USA.
Proc Soc Exp Biol Med. 1998 Apr;217(4):435-8. doi: 10.3181/00379727-217-44253.
Etiocholanolone (5beta-androstan-3alpha-ol-17-one; designated E) is one of the major products of metabolism of testosterone and androstenedione (androst-4-ene-3,17-dione) in many mammalian species, including humans. E and several other 5beta-reduced steroids have been found to induce fever in humans. The pyrogenic effect of these steroids has been shown to be due to the release of interleukin-1 (IL-1) from the leukocytes that are mobilized in response to the steroid injections. Old World Monkeys such as Rhesus monkeys (Macaca mu/atta), metabolize androgens similarly to humans, and E is a normal metabolite. However, New World Monkeys such as Squirrel monkeys (Saimiri sciureus), lack hepatic 5alpha- and 5beta-steroid reductases and excrete androgens primarily in an unaltered state; E is not produced. Therefore, we postulate that Squirrel monkeys likewise may have lost the ability to respond to 17-ketosteroids such as E. To test this hypothesis, adult male Rhesus and Squirrel monkeys were treated with E, and their rectal temperatures were recorded over a 24-hr period. Rhesus monkeys exhibited a rise of up to 3 degrees F following E injection. Squirrel monkeys, on the other hand, did not exhibit any increase in rectal temperature over the 24-hr period, even when doses up to 250 times the effective human dose were used. However, both species responded to injected IL-1alpha with a robust increase in rectal temperature. The data show that E is pyrogenic in Rhesus, but not Squirrel monkeys. The findings support the notion that injected E may induce release of IL-1 in Rhesus monkeys, but not in Squirrel monkeys.
本胆烷醇酮（5β-雄甾烷-3α-醇-17-酮；简称E）是睾酮和雄烯二酮（雄甾-4-烯-3,17-二酮）在包括人类在内的许多哺乳动物物种中的主要代谢产物之一。已发现E和其他几种5β-还原甾体可在人类中引起发热。这些甾体的致热作用已被证明是由于对甾体注射产生反应而动员的白细胞释放白细胞介素-1（IL-1）所致。恒河猴等旧世界猴代谢雄激素的方式与人类相似，E是一种正常代谢产物。然而，松鼠猴等新世界猴缺乏肝脏5α-和5β-甾体还原酶，主要以未改变的状态排泄雄激素；不会产生E。因此，我们推测松鼠猴同样可能失去了对诸如E等17-酮甾体产生反应的能力。为了验证这一假设，成年雄性恒河猴和松鼠猴接受E治疗，并在24小时内记录它们的直肠温度。注射E后，恒河猴的体温升高高达3华氏度。另一方面，即使使用高达有效人类剂量250倍的剂量，松鼠猴在24小时内直肠温度也没有任何升高。然而，两种物种对注射的IL-1α均有直肠温度的显著升高反应。数据表明，E在恒河猴中具有致热作用，但在松鼠猴中则不然。这些发现支持了注射E可能在恒河猴中诱导IL-1释放，但在松鼠猴中则不会的观点。
