Submitted on May 24, 2005
Accepted on December 1, 2005
Basal and evoked levels of bioassayable growth hormone are altered by hindlimb unloading
A. J. Bigbee1, R. E. Grindeland2, R. R. Roy3*, H. Zhong4, K. L. Gosselink4, S. Arnaud2, and V. R. Edgerton5
1 Department of Neurobiology, UCLA, Los Angeles, CA, USA
2 Life Sciences, NASA Ames Research Center, Moffett Field, CA, USA
3 Brain Research Institute, UCLA, Los Angeles, CA, USA
4 Department of Physiological Science, UCLA, Los Angeles, CA, USA
5 Department of Neurobiology, UCLA, Los Angeles, CA, USA; Department of Physiological Science, UCLA, Los Angeles, CA, USA; Brain Research Institute, UCLA, Los Angeles, CA, USA
* To whom correspondence should be addressed. E-mail: rrr{at}ucla.edu.
Bioassayable growth hormone (BGH) in rats is released in large quantities from the pituitary in response to the activation of large, proprioceptive afferent fibers from fast and mixed fiber-type hindlimb musculature. We hypothesized that hindlimb unloading (HU) of adult male rats would 1) reduce the basal levels of plasma BGH, and 2) abolish stimulus-induced BGH release. Rats were exposed to HU for 1, 4, or 8 wks. Plasma and pituitaries were collected under isoflurane anesthesia for hormone analyses. Additionally, at 4 and 8 wks, a subset of rats underwent an in situ electrical stimulation (Stim) of tibial nerve proprioceptive afferents. Basal plasma BGH levels were significantly reduced (-51 and -23%) following 1 and 8 wks of HU compared to ambulatory controls (Amb). While Amb-Stim rats exhibited increased plasma BGH levels (88 and 143%) and decreased pituitary BGH levels (-27 and -22%) at 4 and 8 wks, respectively, stimulation in HU rats had the opposite effect, reducing plasma BGH (-25 and -33%) and increasing pituitary BGH levels (47 and 10%) relative to HU alone at 4 and 8 wks. The 22 kD form of GH measured by immunoassay, and plasma corticosterone, T3, T4, and testosterone levels were unchanged by HU or Stim at all time points. These data suggest that BGH synthesis and release from the pituitary are sensitive both to chronically reduced neuromuscular loading and to acute changes in neuromuscular activation, independent of changes in other circulating hormones. Thus, BGH may play a role in muscle, bone, and metabolic adaptations that occur in response to chronically unloaded states.
