Gonadal steroid regulation of growth-associated protein GAP-43 mRNA expression in axotomized hamster facial motor neurons.
Treatment with testosterone propionate (TP) after nerve injury is known to accelerate both the rate of axonal regeneration and functional recovery from facial paralysis in the adult male hamster. Peripheral nerve injury is also known to increase the expression of a 43 kilodalton growth-associated protein (GAP-43). In the intact brain, GAP-43 expression is affected by gonadal steroids. We thus postulated that steroidal modulation of GAP-43 gene expression may be a component of the neurotrophic action of TP in regenerating neurons. This issue was examined in hamster facial motor neurons (FMN) which contain androgen receptors and which have been shown to respond to exogenous steroids in a number of previous studies. Castrated adult male hamsters were subjected to right facial nerve transection and treated with either TP via subcutaneous hormone capsule implants, or left untreated (no hormone replacement). At post-injury/treatment times of 0.25, 2, 4, 7, and 14 d, the brain stem regions were harvested, cryostat sections were collected through the facial motor nucleus, and in situ hybridization was done using a 33P-labeled GAP-43 cDNA probe. Quantitative analysis of the autoradiograms by computer assisted grain counting revealed that axotomy produced a dramatic increase in GAP-43 mRNA levels in FMN by 2 d post-axotomy and that this increase remained through 14 d post-injury in both the TP-treated and the untreated group. In the nonhormone-treated group, there was a statistically significant dip in GAP-43 mRNA levels in FMN at 7 d post-operative, relative to 4 d post-operative levels. TP-treatment prevented this transient decline in GAP-43 mRNA levels in axotomized FMN.
Jones
K J
KJ
Department of Cell Biology, Neurobiology and Anatomy, Loyola University, Chicago, Maywood, Illinois 60153, USA.
Drengler
S M
SM
Oblinger
M M
MM
D000818:Animals; D001345:Autoradiography; D019771:Axotomy; D006224:Cricetinae; D005154:Facial Nerve / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D020220:Facial Nerve Injuries; D019922:GAP-43 Protein / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008647:Mesocricetus; D009046:Motor Neurons / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis*; D013739:Testosterone / Q000494:pharmacology*
D019922:GAP-43 Protein; D012333:RNA, Messenger; D013739:Testosterone