Abstract

It is well established in animals and humans that the maintenance of normal spermatogenesis is critically dependent upon the presence of androgenic steroids within the testis. Studies in the rodent have shown that intratesticular testosterone concentrations are normally thirty-fold higher than serum concentrations, and that levels of intratesticular testosterone ten-fold greater than serum are required to maintain spermatogenesis. It is incredible that the concentration of testosterone in the normal human testis is not known. The long-term objectives of this project are to study the relationship between intratesticular testosterone concentration and spermatogenesis in humans, and to understand the role that inadequate intratesticular testosterone concentration might play in male infertility. The intratesticular concentration of testosterone, its precursors and metabolites, in normal fertile men will be determined by examining testicular fluid obtained by direct percutaneous aspiration from fertile men undergoing vasectomy. Biologically available intratesticular testosterone will be estimated by simultaneously measuring the intratesticular androgen binding proteins, steroid hormone binding globulin (SHBG) and androgen binding protein (ABP). The range of the minimally necessary intratesticular concentration of testosterone required for the maintenance of quantitatively normal spermatogenesis will be estimated by measuring the intratesticular testosterone concentration of men receiving contraceptive doses of testosterone and men with partial hypogonadism prior to their receiving testosterone replacement therapy. The range of intratesticular testosterone concentration in infertile men diagnosed with idiopathic infertility and with varicoceles will be determined. Additionally, the pathophysiological mechanism for abnormally low intratesticular testosterone concentration will be studied in subfertile men. We will directly test the hypothesis that reduced intratesticular testosterone concentration is responsible for infertility by examining the correlation between intratesticular testosterone concentration and improvement in spermatogenesis in infertile men receiving therapies designed to increase intratesticular testosterone concentration.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54HD036209-01
Application #
6272445
Study Section
Project Start
1998-04-02
Project End
1999-03-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Coviello, Andrea D; Matsumoto, Alvin M; Bremner, William J et al. (2005) Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. J Clin Endocrinol Metab 90:2595-602
Somwaru, Lily; Li, Siming; Doglio, Lynn et al. (2004) Heat-induced apoptosis of mouse meiotic cells is suppressed by ectopic expression of testis-specific calpastatin. J Androl 25:506-13
Coviello, Andrea D; Bremner, William J; Matsumoto, Alvin M et al. (2004) Intratesticular testosterone concentrations comparable with serum levels are not sufficient to maintain normal sperm production in men receiving a hormonal contraceptive regimen. J Androl 25:931-8
Show, Matthew D; Anway, Matthew D; Zirkin, Barry R (2004) An ex vivo analysis of Sertoli cell actin dynamics following gonadotropic hormone withdrawal. J Androl 25:1013-21
Show, Matthew D; Folmer, Janet S; Anway, Matthew D et al. (2004) Testicular expression and distribution of the rat bcl2 modifying factor in response to reduced intratesticular testosterone. Biol Reprod 70:1153-61
Hill, Christine M; Anway, Matthew D; Zirkin, Barry R et al. (2004) Intratesticular androgen levels, androgen receptor localization, and androgen receptor expression in adult rat Sertoli cells. Biol Reprod 71:1348-58
Zhang, Liying; Charron, Martin; Wright, William W et al. (2004) Nuclear factor-kappaB activates transcription of the androgen receptor gene in Sertoli cells isolated from testes of adult rats. Endocrinology 145:781-9
Anway, Matthew D; Wright, William W; Zirkin, Barry R et al. (2004) Expression and localization of cathepsin k in adult rat sertoli cells. Biol Reprod 70:562-9
Show, Matthew D; Anway, Matthew D; Folmer, Janet S et al. (2003) Reduced intratesticular testosterone concentration alters the polymerization state of the Sertoli cell intermediate filament cytoskeleton by degradation of vimentin. Endocrinology 144:5530-6
Anway, Matthew D; Folmer, Janet; Wright, William W et al. (2003) Isolation of sertoli cells from adult rat testes: an approach to ex vivo studies of Sertoli cell function. Biol Reprod 68:996-1002

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