TY - JOUR
T1 - Microencapsulation of Leydig Cells
T2 - A System for Testosterone Supplementation
AU - Machluf, Marcelle
AU - Orsola, Anna
AU - Boorjian, Stephen
AU - Kershen, Richard
AU - Atala, Anthony
PY - 2003/11
Y1 - 2003/11
N2 - The use of testosterone supplementation for elderly men has increased markedly over the last decade due to a recognized gradual decline in serum testosterone, which may lead to decreased bone mass, muscle strength, and libido. Testosterone supplementation is also used widely to treat some forms of erectile dysfunction, androgen deficiency, and infertility. However, long-term exogenous testosterone therapy has been associated with several complications, such as fluid retention, nitrogen retention, and hypertension. Due to these problems, alternate treatment modalities, involving more physiological and longer-acting systems for androgen delivery, have been pursued. Alginate-poly-L-lysine-encapsulated Leydig cell microspheres were used as a novel method for the delivery of testosterone in vivo. Encapsulated Leydig cells, which were stimulated with human chorionic gonadotropin, secreted high levels of testosterone in culture. Unencapsulated cells injected ip or se failed to produce any testosterone levels, even with human chorionic gonadotropin stimulation. Castrated rats that were administered encapsulated Leydig cells ip or sc maintained a serum testosterone level between 0.23 and 0.51 ng/ml. Similar levels of testosterone were obtained for 43 d when the encapsulated Leydig cells were injected sc (0.28-0.48 ng/ml). Approximately 10% of a normal adult rat Leydig cell population was injected into each castrated animal; however, this resulted in serum testosterone levels of up to 40% of normal. Clinically, testosterone is usually delivered for supplementation and not for full replacement therapy. Therefore, the findings of this study suggest that microencapsulated Leydig cells may be a viable option as a therapeutic modality involving testosterone supplementation.
AB - The use of testosterone supplementation for elderly men has increased markedly over the last decade due to a recognized gradual decline in serum testosterone, which may lead to decreased bone mass, muscle strength, and libido. Testosterone supplementation is also used widely to treat some forms of erectile dysfunction, androgen deficiency, and infertility. However, long-term exogenous testosterone therapy has been associated with several complications, such as fluid retention, nitrogen retention, and hypertension. Due to these problems, alternate treatment modalities, involving more physiological and longer-acting systems for androgen delivery, have been pursued. Alginate-poly-L-lysine-encapsulated Leydig cell microspheres were used as a novel method for the delivery of testosterone in vivo. Encapsulated Leydig cells, which were stimulated with human chorionic gonadotropin, secreted high levels of testosterone in culture. Unencapsulated cells injected ip or se failed to produce any testosterone levels, even with human chorionic gonadotropin stimulation. Castrated rats that were administered encapsulated Leydig cells ip or sc maintained a serum testosterone level between 0.23 and 0.51 ng/ml. Similar levels of testosterone were obtained for 43 d when the encapsulated Leydig cells were injected sc (0.28-0.48 ng/ml). Approximately 10% of a normal adult rat Leydig cell population was injected into each castrated animal; however, this resulted in serum testosterone levels of up to 40% of normal. Clinically, testosterone is usually delivered for supplementation and not for full replacement therapy. Therefore, the findings of this study suggest that microencapsulated Leydig cells may be a viable option as a therapeutic modality involving testosterone supplementation.
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U2 - 10.1210/en.2003-0411
DO - 10.1210/en.2003-0411
M3 - Article
C2 - 12960073
AN - SCOPUS:0242468474
SN - 0013-7227
VL - 144
SP - 4975
EP - 4979
JO - Endocrinology
JF - Endocrinology
IS - 11
ER -