Androgenic hormones and human granulopoiesis in vitro.

Androgenic steroids in physiologic concenAnalysis of growth kinetics suggested that trotions were found to stimulate human increased granulopoiesis results from progranulopoiesis in vitro. Testosterone in liferation of committed granulocyte prehigh concentration, but probably within cursors in the marrow rather than stem-cell the range achievable after intensive treatactivation. ment, was found to inhibit granulopoiesis. A NDROGENIC STEROIDS ARE thought to stimulate erythropoiesis both by increasing production of erythropoietin’ and by direct effects on hematopoietic cells.2’3 Clinical experience with androgens in the treatment of aplastic anemia4’5 and during treatment with myelosuppressive agents6’7’t has suggested that these hormones may also stimulate granulopoiesis. In vitro9-’0 and in vivo’#{176}studies of granulopoiesis in testosterone-treated animals have indicated that leukopoiesis is increased, but no experimental model using human marrow cells has demonstrated that androgens effect granulopoiesis in humans. Using the in vitro assay for granulocyte colony formation (CFU-C), we have investigated the response of normal human marrow with and without the addition of testosterone to the culture medium. An increase in CFU-C of 24#{176}, -60#{176},, was observed when the concentration of testosterone reached lO -lO’#{176} M, whereas inhibition of colony formation of 30%-35#{176},, occurred at concentrations of 10-6 M or greater. These experiments confirm a stimulatory effect by androgens on human granulopoiesis. The inhibitory effects noted at higher concentrations may have implications for the clinical use of these compounds in hematologic disorders.