Effect of androgens on the germ cell-depleted testes of prenatally irradiated rats.
To study the effect of androgens on somatic testicular cells, rats were rendered germ cell depleted by prenatal irradiation (RX). Adult RX rats were treated with a desensitizing dose of a GnRH agonist (GnRHa; Zoladex), combined with an antiandrogen (Nilutamide) to preclude all androgen effects, or combined with testosterone or hCG to restore androgen action. The effect of these treatments for 3 weeks on the weight of testes and accessory sex glands, hormones (LH, FSH, testosterone, inhibin), testicular proteins, the pattern of incorporation of [35S]-methionine into testicular proteins (studied by two dimensional gel electrophoresis) and steady state mRNA levels for transferrin and androgen-binding protein (ABP) were evaluated. Combined treatment with GnRHa and antiandrogen virtually eliminated gonadotrophins, androgens and androgen effects. Testicular weight was reduced to 50% of that observed in RX controls. Treatment with GnRHa and testosterone resulted in supraphysiological levels of testosterone and testicular weights comparable to those observed in RX controls. FSH levels in these animals, however, were in the normal range. A low dose of hCG also restored testicular weight in the presence of low concentrations of serum testosterone and low normal levels of FSH. Neither polyacrylamide gel electrophoresis of total testicular proteins nor two dimensional gel electrophoresis of [35S]-methionine labelled proteins revealed striking changes in distinct testicular proteins as a result of androgen withdrawal or androgen treatment. Dot blot hybridization showed a three-fold increase in the mRNA level for ABP (expressed per microgram total RNA) in the Sertoli cell enriched testes of RX rats. This level was barely influenced by androgen withdrawal or androgen administration. The mRNA level for transferrin was increased six-fold in RX rats. A 50% reduction of this level was observed after combined treatment with GnRHa and antiandrogen. It is concluded that, in the germ cell-depleted testis, the major effect of androgens is an overall increase in protein and RNA synthesis rather than a very important and selective increase of a few gene products.
Verhoeven
G
G
Laboratory for Experimental Medicine and Endocrinology, Onderwijs en Navorsing, Gasthuisberg, Catholic University of Leuven, Belgium.
Deboel
L
L
Swinnen
J
J
Rombauts
L
L
Vanderhoydonc
F
F
Rosseels
J
J
Hoeben
E
E
Heyns
W
W
D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D017931:DNA Primers; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D017273:Goserelin / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D009929:Organ Size / Q000187:drug effects / Q000528:radiation effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014176:Protein Biosynthesis; D011506:Proteins / Q000528:radiation effects; D012313:RNA / Q000096:biosynthesis / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D013094:Spermatozoa / Q000528:radiation effects; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D013739:Testosterone / Q000494:pharmacology
D000726:Androgen Antagonists; D000728:Androgens; D017931:DNA Primers; D007093:Imidazoles; D048289:Imidazolidines; D011506:Proteins; D017273:Goserelin; D013739:Testosterone; C021277:nilutamide; D012313:RNA; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone