Site and Mode of Action of Indomethacin on the Hypothalamo-Hypophyseal-Adrenal Axis: A Temporal Study in Intact, Hypothalamic-Deafferentated, and Hypothalamic-Lesioned Male Rats*

Abstract

Adult male rats were given single sc injections of indomethacin (IM; 5 mg/100 g BW) and sacrificed 2–24 h later. IM effects upon serum ACTH and corticosterone (CS) levels, rectal temperature, and hypothalamic and adenohypophyseal prostaglandin E₂ (PGE₂) and cAMP contents were observed. Rectal temperature was normal for 5–10 h post injection and later decreased by approximatley 2.5 C. Both hypothalamic and adenohypophyseal PGE₂ concentrations were reduced from 2– 24 h after IM administration; no changes in cAMP content were observed. Serum ACTH and CS levels were elevated 4- and 6- fold, respectively, over the entire period observed. In animals with complete hypothalamic deafferentations, the ACTH and CS responses to IM were as marked as they were in intact rats. In rats with hypothalamic lesions in which the ACTH and CS responses to ether stress were attenuated, marked ACTH and CS secretory responses to IM were seen. It is concluded: 1) that the main site of action of systemically administered IM on the hypothalamohypophyseal-adrenal axis, is within the adenohypophysis; 2) that this effect is mediated by PGE₂, and cAMP is not involved; and 3) that central nervous system PGs may be involved in the maintenance of basal body temperature in the rat.