squeegee
Banned
- Reaction score
- 132
Dihydrotestosterone induces SREBP-1 expression
and lipogenesis through the phosphoinositide
3-kinase/Akt pathway in HaCaT cells
http://www.lipidworld.com/content/pdf/1476-511X-11-156.pdf
IntroductionExcessive secretion of sebum on skin is an important
factor in various skin diseases, including acne and sebor-
rheic dermatitis [1,2]. Besides sebaceous glands, kerati-
nocytes are another important source of lipid on skin
surface (2). Although the epidermis is certainly affected
by steroid hormones, little is known about the effects of
androgens on human keratinocytes. Previous studies
demonstrated that in sebaceous glands androgens regu-
lates the synthesis of sebum lipids through the sterol
regulatory element-binding protein (SREBP) pathway [3].
Nevertheless, results of investigations on androgens re-
ceptor expression in keratinocytes are controversial: some
groups have demonstrated that the androgens receptor is
expressed in the epidermis [4], while others reported its
absence [5]. Although nothing in the literature so far sug-
gests that testosterone or its analog dihydrotestosterone
(DHT) effect the growth of keratinocytes, we found that
these hormones were associated with SREBP-1 expression
in cells of the immortalized keratinocyte cell line HaCaT,
which are quite similar to primary normal keratinocytes
in steroid-metabolizing activity and responsiveness to
steroid hormones [6].
The SREBP transcription factors bind sterol response
elements, and three members of the SREBP family have
been identified: SREBP-1a, SREBP-1c, and SREBP-2 [7].
In spite of the partial functional overlap between
SREBP-1 and SREBP-2, SREBP-1 typically regulates
genes in the fatty acid biosynthesis pathway, whereas
SREBP-2 modulates the transcription of genes asso-
ciated with cholesterol biosynthesis [8]. DHT has been
reported to regulates SREBP-1 expression in various
cell lines and organs [3,9,10]. Besides that, SREBP-1
was also found to be expressed in keratinocytes and
played an important role in its lipid synthesis [11].
However, little is known of how DHT impacts the
function of SREBP-1 in keratinocyte HaCaT cells. The
aim of this study was to dissect the molecular signaling
pathways by which DHT stimulation increases the
mRNA and protein levels of SREBP-1 in HaCaT cells
and lipogenesis through the phosphoinositide
3-kinase/Akt pathway in HaCaT cells
http://www.lipidworld.com/content/pdf/1476-511X-11-156.pdf
IntroductionExcessive secretion of sebum on skin is an important
factor in various skin diseases, including acne and sebor-
rheic dermatitis [1,2]. Besides sebaceous glands, kerati-
nocytes are another important source of lipid on skin
surface (2). Although the epidermis is certainly affected
by steroid hormones, little is known about the effects of
androgens on human keratinocytes. Previous studies
demonstrated that in sebaceous glands androgens regu-
lates the synthesis of sebum lipids through the sterol
regulatory element-binding protein (SREBP) pathway [3].
Nevertheless, results of investigations on androgens re-
ceptor expression in keratinocytes are controversial: some
groups have demonstrated that the androgens receptor is
expressed in the epidermis [4], while others reported its
absence [5]. Although nothing in the literature so far sug-
gests that testosterone or its analog dihydrotestosterone
(DHT) effect the growth of keratinocytes, we found that
these hormones were associated with SREBP-1 expression
in cells of the immortalized keratinocyte cell line HaCaT,
which are quite similar to primary normal keratinocytes
in steroid-metabolizing activity and responsiveness to
steroid hormones [6].
The SREBP transcription factors bind sterol response
elements, and three members of the SREBP family have
been identified: SREBP-1a, SREBP-1c, and SREBP-2 [7].
In spite of the partial functional overlap between
SREBP-1 and SREBP-2, SREBP-1 typically regulates
genes in the fatty acid biosynthesis pathway, whereas
SREBP-2 modulates the transcription of genes asso-
ciated with cholesterol biosynthesis [8]. DHT has been
reported to regulates SREBP-1 expression in various
cell lines and organs [3,9,10]. Besides that, SREBP-1
was also found to be expressed in keratinocytes and
played an important role in its lipid synthesis [11].
However, little is known of how DHT impacts the
function of SREBP-1 in keratinocyte HaCaT cells. The
aim of this study was to dissect the molecular signaling
pathways by which DHT stimulation increases the
mRNA and protein levels of SREBP-1 in HaCaT cells