Distinct effects of gonadectomy in male and female mice on collagen fibrillogenesis in the skin.
BACKGROUND
Collagen biosynthesis and deposition is a complex, multistep process, which is tightly regulated to maintain proper tissue homeostasis. Sex steroid hormones have been implicated in regulating collagen synthesis; however the specific mechanisms regulating the process remain largely unknown.


OBJECTIVE
To investigate the role of estrogens and androgens in the regulation of genes involved in collagen synthesis and fibrillogenesis using gonadectomized C57/B6 mice.


METHODS
Collagen content was assessed by hydroxyproline measurement and acetic acid extraction of collagen with or without the addition of pepsin. The mRNA levels of fibrillar collagens and enzymes involved in fibrillogenesis were determined by QPCR analysis. The protein expression of decorin, lumican and fibromodulin was confirmed by immunostaining.


RESULTS
We have shown that castration resulted in a markedly decreased skin thickness and collagen content without affecting collagen solubility. Furthermore, the mRNA levels of fibrillar collagen genes including types I, III, and V were decreased, suggesting that androgens positively regulate the rate of collagen gene transcription. Conversely, ovariectomy mainly affected collagen solubility. The absence of estrogens resulted in decreased expression levels of several of the small leucine-rich repeat proteins and proteoglycans (SLRPs) including decorin, fibromodulin and lumican.


CONCLUSIONS
Estrogens may not be directly involved in the regulation of collagen synthesis; however, they may play a critical role in regulating organization and stability of collagen fibrils. Androgens play a positive role in the regulation of collagen biosynthesis. In summary, our data demonstrate that androgens and estrogens regulate distinct aspects of collagen fibrillogenesis in mouse skin.
Markiewicz
Margaret
M
Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA. markiewi@musc.edu
Asano
Yoshihide
Y
Znoyko
Sergey
S
Gong
Yong
Y
Watson
Dennis K
DK
Trojanowska
Maria
M
D000818:Animals; D002369:Castration; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis; D003094:Collagen / Q000378:metabolism*; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005260:Female; D000071235:Fibromodulin; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D007632:Keratan Sulfate / Q000096:biosynthesis; D000071234:Lumican; D008297:Male; D051379:Mice; D010052:Ovariectomy; D010434:Pepsin A / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012737:Sex Factors; D012867:Skin / Q000378:metabolism*
D011508:Chondroitin Sulfate Proteoglycans; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604332:Fmod protein, mouse; D012739:Gonadal Steroid Hormones; C000604307:Lum protein, mouse; D000071234:Lumican; D011509:Proteoglycans; D012333:RNA, Messenger; D000071235:Fibromodulin; D003094:Collagen; D007632:Keratan Sulfate; D010434:Pepsin A