Abstract
Certain beta 2-adrenoceptor agonists, such as clenbuterol, are known to elicit a muscle-specific anabolism or hypertrophy in both normal and catabolic muscle in a wide variety of species. However, the underlying mechanism(s) of the beta 2-agonist-induced anabolism remains unclear. This study aimed to determine the effects of clenbuterol administration in utero on skeletal muscle and to examine the underlying molecular mechanisms. Pregnant rats were fed clenbuterol (2 mg/kg diet) from Day 4 of gestation (4 dg) until weanling and fetal samples were taken from 13.5, 15.5, 17.5, and 19.5 dg and from 1d neonatal pups. Muscles were analyzed for total DNA, RNA and protein and sections examined morphologically for changes in muscle development. Western and immunohistochemical analyses were performed to identify changes in known myogenic signaling proteins, Clenbuterol increased the size of both fast and slow fibers in utero which was associated with a decreased DNA:protein ratio (28%) and an increased RNA:DNA ratio (36%). Additionally, drug treatment in utero induced a decrease in the fast:slow fiber ratio (38%). These myogenic changes were correlated with an increase in the GATA-2 hypertrophic transcription factor at both 17.5 dg (by 250%) and 19.5 dg (by 40%) in fetuses from clenbuterol treated dams. In addition, drug treatment resulted in increased membrane association of PKC-mu at 17.5 dg (325%) and increased PKC-alpha cytosolic abundance (40%) and PKC-theta membrane abundance at 19.5 dg (250%). These results are the first demonstration that beta 2-agonists such as clenbuterol may act through upregulating the GATA-2 transcription factor and implicate certain PKC isoforms in the drug-induced regulation of skeletal muscle development. Mol. Reprod. Dev. 75: 785-794, 2008. (C) 2007 Wiley-Liss, lnc.
| Original language | English |
|---|---|
| Pages (from-to) | 785-794 |
| Number of pages | 10 |
| Journal | Molecular Reproduction and Development |
| Volume | 75 |
| Issue number | 5 |
| Early online date | 18 Oct 2007 |
| DOIs | |
| Publication status | Published - May 2008 |
Keywords
- beta-adrenergic agonist
- hypertrophy
- anabolism
- fetal
- kinase-C
- agonist clenbuterol
- gene-expression
- PKC-theta
- growth
- beta
- differentiation
- stimulation
- atrophy
- ß-adrenergic agonist
Cite this
Clenbuterol increases muscle fiber size and GATA-2 protein in rat skeletal muscle in utero. / Downie, Diane; Delday, Margaret I.; Maltin, Charlotte A.; Sneddon, Alan A.
In: Molecular Reproduction and Development, Vol. 75, No. 5, 05.2008, p. 785-794.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clenbuterol increases muscle fiber size and GATA-2 protein in rat skeletal muscle in utero
AU - Downie, Diane
AU - Delday, Margaret I.
AU - Maltin, Charlotte A.
AU - Sneddon, Alan A.
PY - 2008/5
Y1 - 2008/5
N2 - Certain beta 2-adrenoceptor agonists, such as clenbuterol, are known to elicit a muscle-specific anabolism or hypertrophy in both normal and catabolic muscle in a wide variety of species. However, the underlying mechanism(s) of the beta 2-agonist-induced anabolism remains unclear. This study aimed to determine the effects of clenbuterol administration in utero on skeletal muscle and to examine the underlying molecular mechanisms. Pregnant rats were fed clenbuterol (2 mg/kg diet) from Day 4 of gestation (4 dg) until weanling and fetal samples were taken from 13.5, 15.5, 17.5, and 19.5 dg and from 1d neonatal pups. Muscles were analyzed for total DNA, RNA and protein and sections examined morphologically for changes in muscle development. Western and immunohistochemical analyses were performed to identify changes in known myogenic signaling proteins, Clenbuterol increased the size of both fast and slow fibers in utero which was associated with a decreased DNA:protein ratio (28%) and an increased RNA:DNA ratio (36%). Additionally, drug treatment in utero induced a decrease in the fast:slow fiber ratio (38%). These myogenic changes were correlated with an increase in the GATA-2 hypertrophic transcription factor at both 17.5 dg (by 250%) and 19.5 dg (by 40%) in fetuses from clenbuterol treated dams. In addition, drug treatment resulted in increased membrane association of PKC-mu at 17.5 dg (325%) and increased PKC-alpha cytosolic abundance (40%) and PKC-theta membrane abundance at 19.5 dg (250%). These results are the first demonstration that beta 2-agonists such as clenbuterol may act through upregulating the GATA-2 transcription factor and implicate certain PKC isoforms in the drug-induced regulation of skeletal muscle development. Mol. Reprod. Dev. 75: 785-794, 2008. (C) 2007 Wiley-Liss, lnc.
AB - Certain beta 2-adrenoceptor agonists, such as clenbuterol, are known to elicit a muscle-specific anabolism or hypertrophy in both normal and catabolic muscle in a wide variety of species. However, the underlying mechanism(s) of the beta 2-agonist-induced anabolism remains unclear. This study aimed to determine the effects of clenbuterol administration in utero on skeletal muscle and to examine the underlying molecular mechanisms. Pregnant rats were fed clenbuterol (2 mg/kg diet) from Day 4 of gestation (4 dg) until weanling and fetal samples were taken from 13.5, 15.5, 17.5, and 19.5 dg and from 1d neonatal pups. Muscles were analyzed for total DNA, RNA and protein and sections examined morphologically for changes in muscle development. Western and immunohistochemical analyses were performed to identify changes in known myogenic signaling proteins, Clenbuterol increased the size of both fast and slow fibers in utero which was associated with a decreased DNA:protein ratio (28%) and an increased RNA:DNA ratio (36%). Additionally, drug treatment in utero induced a decrease in the fast:slow fiber ratio (38%). These myogenic changes were correlated with an increase in the GATA-2 hypertrophic transcription factor at both 17.5 dg (by 250%) and 19.5 dg (by 40%) in fetuses from clenbuterol treated dams. In addition, drug treatment resulted in increased membrane association of PKC-mu at 17.5 dg (325%) and increased PKC-alpha cytosolic abundance (40%) and PKC-theta membrane abundance at 19.5 dg (250%). These results are the first demonstration that beta 2-agonists such as clenbuterol may act through upregulating the GATA-2 transcription factor and implicate certain PKC isoforms in the drug-induced regulation of skeletal muscle development. Mol. Reprod. Dev. 75: 785-794, 2008. (C) 2007 Wiley-Liss, lnc.
KW - beta-adrenergic agonist
KW - hypertrophy
KW - anabolism
KW - fetal
KW - kinase-C
KW - agonist clenbuterol
KW - gene-expression
KW - PKC-theta
KW - growth
KW - beta
KW - differentiation
KW - stimulation
KW - atrophy
KW - ß-adrenergic agonist
U2 - 10.1002/mrd.20795
DO - 10.1002/mrd.20795
M3 - Article
VL - 75
SP - 785
EP - 794
JO - Molecular Reproduction and Development
JF - Molecular Reproduction and Development
SN - 1040-452X
IS - 5
ER -