Effects of axotomy and testosterone on androgen receptor mRNA expression in hamster facial motoneurons.
We have previously demonstrated that testosterone propionate (TP) treatment accelerates the rate of regeneration following facial nerve crush axotomy in adult male hamsters. These effects are mediated by androgen receptor (AR) activation and are blocked by pretreatment with the AR antagonist, flutamide. In addition to its beneficial effects on regeneration, TP regulates AR mRNA levels in facial motor neurons (FMN). Gonadectomized (gdx) male hamsters have been shown to have approximately 50% of the AR mRNA levels found in gonadally intact males. Administration of TP to gdx males results in an upregulation in AR mRNA levels after 1 day of treatment. Recent reports in the literature suggest that axotomy also may regulate the expression of AR in motor neurons. In this study, we examined the effects of axotomy and exogenous steroid treatment on the regulation of AR mRNA in hamster FMN. Five days after castration, adult male hamsters were subjected to a right facial nerve axotomy. Half the animals received one 10-mm Silastic capsule filled with 100% crystalline TP, and the remainder were sham implanted. Postoperative survival times were 6 h or 1, 2, 4, 7, or 14 days. In situ hybridization in conjunction with an AR riboprobe and computerized image analysis were used to quantify AR mRNA levels. The contralateral FMN served as internal controls for these experiments, and FMN of gonadally intact males served as additional nonaxotomized controls. As predicted, AR mRNA levels were upregulated in contralateral control FMN after TP treatment. However, this TP-induced upregulation of AR mRNA levels did not occur in the axotomized FMN. These results indicate that axonal injury can disrupt the normal regulatory pattern of AR mRNA expression by exogenous steroids in motoneurons. We conclude that the potentiation of regenerative events by TP does not require augmented synthesis of AR, but, instead, enhanced stabilization of existing receptors.
Drengler
S M
SM
Department of Cell Biology, Neurobiology and Anatomy, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois 60153, USA.
Handa
R J
RJ
Jones
K J
KJ
D000818:Animals; D001345:Autoradiography; D001369:Axons / Q000502:physiology*; D006224:Cricetinae; D003714:Denervation; D005154:Facial Nerve / Q000166:cytology / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D008647:Mesocricetus; D009046:Motor Neurons / Q000378:metabolism*; D009919:Orchiectomy; D012333:RNA, Messenger / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics*; D013739:Testosterone / Q000494:pharmacology*
D012333:RNA, Messenger; D011944:Receptors, Androgen; D013739:Testosterone