title: The effects of a gonadotropin-releasing hormone antagonist on androgen-binding protein distribution and other parameters in the adult male rat.
abstract: The effects of gonadotropins and gonadal steroids on androgen-binding protein (ABP) production and its distribution among the epididymis, seminiferous tubule fluid (STF), testicular interstitial fluid (TIF), and blood were studied in 300-g adult male Sprague-Dawley rats. The rats either received no treatment or their pituitary function was suppressed by administration of the GnRH antagonist [AcD2Nal,D4ClDPhe2,D3Pal3,Arg5,DGlu6 (AA),D-Ala10]LHRH (antagonist). Other groups of rats were treated with hCG, FSH, FSH plus hCG, testosterone, or estradiol, alone or together with antagonist. Treatment was conducted for 30 days, after which time, ABP was detected by its ability to bind [3H]5 alpha-dihydrotestosterone. Transport of ABP from the testis to the epididymis was inhibited by antagonist administration. Simultaneous treatment with antagonist and hCG, or antagonist and hCG plus FSH prevented antagonist-induced inhibition of ABP transport. Neither FSH, testosterone, nor estradiol alone was effective in this process. Inhibition of ABP transport to the epididymis was accompanied by its accumulation within the testis. Treatment with antagonist and FSH resulted in a 4.5-fold increase in the concentration of ABP in TIF, but had little effect on the amount of ABP in STF, indicating selective secretion of ABP from the basal surface of the Sertoli cells. Treatment with antagonist alone, antagonist together with testosterone or estradiol, or estradiol alone resulted in increased concentrations of ABP in both TIF and STF, but the increase in TIF was proportionately greater. Treatment with hCG or FSH plus hCG alone or with antagonist not only facilitated ABP transport to the epididymis, but also increased TIF levels of ABP above control values. The former treatment resulted in increased concentrations of testosterone in TIF, but not in STF. Both treatments resulted in testosterone levels in both compartments that were higher than those in animals treated with antagonist alone. No treatment had a statistically significant effect on blood levels of ABP. About 50% of ABP synthesis appears to be constitutive, i.e. is not regulated by hormones. Although ABP production continues in the presence of antagonist, its transport to the epididymis is halted, indicating that epididymal transport of ABP is a hormone-dependent process. It is likely that elevated intratesticular levels of testosterone or FSH and testosterone acting in concert regulate epididymal transport of ABP.
authors.affiliation: Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2633, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Danzo
mesh_terms: D000727:Androgen-Binding Protein / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004822:Epididymis / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012671:Seminiferous Tubules / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism; D013737:Testis / Q000033:anatomy & histology / Q000737:chemistry* / Q000378:metabolism; D013739:Testosterone / Q000097:blood* / Q000494:pharmacology
chemical_list: D000727:Androgen-Binding Protein; D006063:Chorionic Gonadotropin; C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone