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Abstract

Rapid glucocorticoid mediation of suppressed testosterone biosynthesis in male mice subjected to immobilization stress 
Dong,Qiang; Salva,Antonio; Sottas,Chantal M.; Niu,Enmei; Holmes,Michael; Hardy,Matthew P.
Journal of Andrology 25(6): 973-981
Publication date: 2004


Physical and psychosocial stress challenge homeostasis, increasingglucocorticoid secretion (in rodents, corticosterone [CORT])while decreasing testosterone (T) levels. The dynamics of stress-inducedchanges in T, CORT, and luteinizing hormone (LH) concentrationsin mice have not been investigated previously. In particular,it remains to be established whether there is a rapid effectof CORT that is directly mediated by glucocorticoid receptors(GRs) in the testis. Therefore, serum and intratesticular T,serum CORT, and LH levels were measured during acute immobilization(IMO) stress, using the C57BL/6 strain of mice. The effectsof testicular GR blockade were investigated by administrationof the GR antagonist, RU486, via intratesticular (IT) or intraperitoneal(IP) injection. CORT levels increased in stressed males startingat 15 minutes, reaching a fivefold higher plateau by 1 hourcompared with controls (P < .01). Conversely, starting from30 minutes on, both serum and intratesticular T levels decreasedin stressed males to 30% and 8% of control values, respectively,by 6 hours (P < .01). In contrast, LH was unchanged by IMOstress for up to 6 hours. Intratesticular treatment with RU486partially prevented the IMO-induced decline in T levels. CORTtreatment reduced intracellular cyclic adenosine monophosphate(cAMP) content in Leydig cells by 15 minutes and T productionby 30 minutes in vitro. We conclude that 1) the rapid changesin T suggest a suppression of T biosynthesis by glucocorticoidthrough a nongenomic mechanism, lowering the production ofcytoplasmic cAMP; 2) changes in gonadotropic stimulation ofLeydig cells are unlikely to explain the suppression of T levelsduring acute stress; and 3) the results are consistent witha direct inhibitory action of CORT on Leydig cells.