title: Decrease of core body temperature in mice by dehydroepiandrosterone.
abstract: Dietary dehydroepiandrosterone (DHEA) reduces food intake in mice, and this response is under genetic control. Moreover, both food restriction and DHEA can prevent or ameliorate certain diseases and mediate other biological effects. Mice fed DHEA (0.45% w/w of food) and mice pair-fed to these mice (food restricted) for 8 weeks were tested for changes in body temperature. DHEA was more efficient than food restriction alone in causing hypothermia. DHEA injected intraperitoneally also induced hypothermia that reached a nadir at 1 to 2 hr, and slowly recovered by 20 to 24 hr. This effect was dose dependent (0.5-50 mg). Each mouse strain tested (four) was susceptible to this effect, suggesting that the genetics differ for induction of hypophagia and induction of hypothermia. Because serotonin and dopamine can regulate (decrease) body temperature, we treated mice with haloperidol (dopamine receptor antagonist), 5,7-dihydroxytryptamine (serotonin production inhibitor), or ritanserin (serotonin receptor antagonist) prior to injection of DHEA. All of these agents increased rather than decreased the hypothermic effects of DHEA. DHEA metabolites that are proximate (5-androstene-3beta, 17beta-diol and androstenedione) or further downstream (estradiol-17beta) were much less effective than DHEA in inducing hypothermia. However, the DHEA analog, 16alpha-chloroepiandrosterone, was as active as DHEA. Thus, DHEA administered parentally seems to act directly on temperature-regulating sites in the body. These results suggest that DHEA induces hypothermia independent of its ability to cause food restriction, to affect serotonin or dopamine functions, or to act via its downstream steroid metabolites.
authors.affiliation: Departments of Pathology, Obstetrics and Gynecology, and Academic Computing Services, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9072, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Catalina
authors.forename: Leon
authors.initials: L
authors.lastname: Milewich
authors.forename: William
authors.initials: W
authors.lastname: Frawley
authors.forename: Vinay
authors.initials: V
authors.lastname: Kumar
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000738:Androsterone / Q000096:biosynthesis; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004032:Diet; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D007035:Hypothermia / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors
chemical_list: D018492:Dopamine Antagonists; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D016713:Ritanserin; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D003687:Dehydroepiandrosterone; D000738:Androsterone; D006220:Haloperidol; D004298:Dopamine