Regulation of androgen receptor mRNA and protein in the rat testis by testosterone.
Adult rats were treated with ethane dimethane sulphonate (EDS), an agent that destroys Leydig cells. Within 5 days after EDS treatment, the levels of testosterone (T) in the circulation and in the testis were decreased to very low values, which makes it possible to manipulate the testicular T concentration through administration of exogenous T. Spermatogenesis was not markedly affected within 5 days after EDS treatment, also not in the absence of T administration. In testes of EDS-treated rats, the androgen receptor mRNA (ARmRNA) level remained unaltered for 5 days. In ventral prostate, however, this treatment caused a pronounced upregulation of the level of ARmRNA, which could be counteracted by implantation of silastic T implants immediately after EDS treatment. In EDS-treated rats carrying a T implant and in untreated rats, the same number of specific [3H]R1881 binding sites was observed using a total testis nuclear fraction (Scatchard analysis). In testes from EDS-treated rats without T implants, androgen receptors (AR) did not fractionate into the nuclear fraction; however, the total testicular AR content in these animals (measured by nuclear [3H]R1881 binding after receptor transformation through injection of a high dose of T, 2 h before killing the rats) remained unaltered. Immunoprecipitation and Western blotting using anti N-terminal antibodies seemed to indicate that the total testicular amount of AR protein in the EDS-treated rats was very low as compared to that in EDS-treated rats carrying T implants and in untreated rats. Even after receptor retransformation (by injection of a high dose of T) the receptors were not quantitatively detected by immunoprecipitation and Western blotting. This may point to a structural modification of the AR that occurs in the prolonged absence of androgens.
Block
L J
LJ
Department of Endocrinology and Reproduction, Medical Faculty, Erasmus University Rotterdam, The Netherlands.
Bartlett
J M
JM
Bolt-de Vries
J
J
Themmen
A P
AP
Brinkmann
A O
AO
Weinbauer
G F
GF
Nieschlag
E
E
Grootegoed
J A
JA
D000728:Androgens / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D005640:Follicle Stimulating Hormone / Q000502:physiology; D008297:Male; D008698:Mesylates / Q000494:pharmacology; D011233:Precipitin Tests; D011467:Prostate / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011944:Receptors, Androgen / Q000235:genetics*; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism / Q000502:physiology*
D000728:Androgens; D008698:Mesylates; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013739:Testosterone; D005640:Follicle Stimulating Hormone; C002994:ethylene dimethanesulfonate