Article Text

PDF
382 TESTOSTERONE PRODUCTION OF ISOLATED LEYDIG CELLS IN XXY MICE.
  1. M. D. Schwarcz1,
  2. Y. H. Lue1,
  3. C. Wang1,
  4. R. S. Swerdloff1
  1. 1LABiomed at Harbor-UCLA Medical Center, Torrance, CA.

Abstract

Introduction Klinefelter's syndrome (KS) is the most common sex chromosome aneuploidy and affects approximately 0.5% of the population. Our center has developed a mouse model that has phenotypic similarities with human XXY counterparts, presenting a unique opportunity to study the molecular mechanisms of Klinefelter's syndrome. The XXY mice also have hypergonadotropic hypogonadism typically found in the disorder, which is highly suggestive of a Leydig cell steroidogenic defect. We have demonstrated that the Leydig cells in XXY mouse testes are both hypertrophic and hyperplastic, similar to men with Klinefelter's syndrome. Our study objective was to determine Leydig cell production of T in vitro in XXY mice compared with XY mice.

Methods Leydig cells from seven adult XXY and seven XY littermate mice were isolated. Aliquots of 20,000 pooled XY or XXY Leydig cells were cultured in each well, respectively. A total of 9 wells of XXY and 40 wells of XY Leydig cells were used in this study. Groups of 5 wells XXY or 20 wells XY Leydig cells were cultured for 3 hours at 37°C. The remaining wells from each group received high-dose (100 ng/mL) LH stimulation. The supernatant testosterone concentration was measured by a specific radioimmunoassay.

Results We showed a 2.5-fold decrease in XXY production of T (XXY 107.9 ± 29.2 ng/dL/105 cells) compared with XY (265.2 ± 94.3 ng/dL/105 cells) in nonstimulated Leydig cells. In response to in vitro high-dose LH 100 ng/mL) stimulation, the T production in XXY (1,287.1 ± 129.8 ng/dL/105 cells) appeared decreased in comparison with XY Leydig cells (1,524.9 ± 228.3 ng/dL/105 cells). Thus, we demonstrated that the testosterone production in XXY Leydig cells was impaired as in their human counterparts with Klinefelter's syndrome. To gain greater insight into the disorder of T production in XXY aneuploidy, we will perform more detailed dose-response curves, study steroidogenic enzymes expression and activity, and unravel responsible X-linked and regulated molecules, which are important in understanding hypogonadism in Klinefelter's syndrome.

Statistics from Altmetric.com

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.