Dihydrotestosterone regulation of thymocyte function in the rat mediation by serum factors.

We have previously reported that reticuloepithelial cells of rat thymic tissue contain specific, high-affinity estrogen (E) and dihydrotestosterone (DHT) receptors which are not present in thymocytes, and that stimulation of the concanavalin A (Con A) sensitive thymocyte population is by means of a thymic serum substance depressed by estradiol. To ascertain if a serum substance modulated by DHT could also effect a thymocyte population, we incubated thymocytes in vitro for 3 days in the presence of the mitogens Con A or phytohaemagglutinin (PHA) + tissue culture media + 20% specific rat serum preparations and pulse labelled with tritiated thymidine. Rat serum samples were prepared from control, castrate, thymectomized (Tx) and castrate-Tx animals as well as from similar groups of animals treated in vitro for 3 days with physiological doses of DHT. It was found that there was a significant enhancement of thymocyte blastogenesis in cultures incubated with castrate rat serum + Con A or PHA vs control serum cultures (P less than 0.001). Direct replacement of DHT either to normal or castrate sera in vitro at physiological concentrations did not alter the level of thymocyte blastogenesis from normal or castrate controls. Sera prepared from castrate animals treated with DHT at physiological concentrations did not depress the blastogenic response, but sera from animals treated with testosterone were successful in depressing the blastogenic response to noncastrate levels. Sera prepared from Tx animals were stimulatory on thymocyte blastogenesis when PHA were utilized (P less than 0.02) and this stimulation was depressed in sera from animals treated in vivo with DHT. Sera prepared from Tx or castrate-Tx animals were not able to stimulate thymocyte blastogenesis when Con A was utilized but were stimulatory when prepared from castrate-Tx animals pretreated in vivo with DHT. It is hypothesized that Con A sensitive thymocytes are depressed by a thymic serum factor under the control of E and that both Con A and PHA sensitive thymocytes are depressed by a serum factor possibly of extrathymic origin that is under the control of DHT. A tentative hypothesis for the regulation of thymocytes by gonadal steroid hormones is presented.