Exogenous androgen treatment delays the stress response following hamster facial nerve injury.
Following injury or stress of any type, cells undergo a stress response, involving the cessation of general protein synthesis and the up-regulation of heat shock proteins (HSP), which have been implicated in promoting cell survival and repair. In a variety of neuronal injury models, including the hamster facial motoneurone (FMN) model, steroid hormones augment regeneration and are neuroprotective. We have previously shown that facial nerve axotomy induces expression of HSP70 (HSP70) and/or up-regulates constitutively expressed HSP70 (HSC70) mRNA in axotomised hamster FMN and that testosterone propionate (TP) treatment reduces this response. These previous studies were unable to differentiate between HSC70 mRNA and HSP70 mRNA. Therefore, an objective of the present study was to determine which HSP (HSC70 or HSP70) was being up-regulated by axotomy and reduced by TP. Axotomy increased HSC70 protein in axotomised and non-axotomised FMN, relative to untreated baseline hamsters. Interestingly, TP transiently delayed the stress-induced up-regulation of HSC70 protein in axotomised FMN compared to axotomised FMN from non-TP treated controls. A potential explanation for this delay may involve the TP-induced liberation of HSP from the androgen receptor, which would provide the injured cell with an immediately available pool of protective HSP. An hypothesis is presented suggesting that this TP-induced delay of stress-induced HSC70 up-regulation might allow for the diversion of cellular energy away from HSP synthesis and towards the synthesis of proteins required for regeneration and survival.
Tetzlaff
J
J
Neuroscience Graduate Program, Loyola University Chicago, Chicago, IL, USA.
Tanzer
L
L
Jones
K J
KJ
D000222:Adaptation, Physiological; D000818:Animals; D019771:Axotomy; D002470:Cell Survival / Q000502:physiology; D006224:Cricetinae; D005154:Facial Nerve / Q000166:cytology / Q000378:metabolism; D020220:Facial Nerve Injuries / Q000378:metabolism*; D005786:Gene Expression Regulation; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013314:Stress, Mechanical; D013739:Testosterone / Q000502:physiology*; D013997:Time Factors
D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D013739:Testosterone