Abstract
Androgens are an integral part of human physiology. The de novo production of androgens is generally limited to the adrenal cortex and the gonads. Androgen synthesis by these steroidogenic tissues requires the bifunctional enzyme cytochrome P450c17, which catalyzes both 17 hydroxylase and 17,20 lyase activities. 17,20-lyase activity is relevant to the regulation of androgen production, and is allosterically modulated through the action of an accessory protein, cytochrome b5 (CytB5). Our objective was to determine the cellular localization of P450c17 and CytB5 in androgen-synthesizing tissues of the human. Immunohistochemical analyses of P450c17 and CytB5 were performed on fetal and adult human adrenals, ovaries, and testes. In the fetal adrenal, CytB5 and P450c17 were both found in the cells of the fetal zone, but not in the neocortex. In the adult adrenal, the zona fasciculata was immunoreactive for P450c17 only, whereas the zona reticularis was immunopositive for both P450c17 and CytB5. In the adult gonads, P450c17 and CytB5 were colocalized in the Leydig cells of the testis, theca interna cells of the follicle, theca lutein cells, and isolated cell clusters in the ovarian stroma. Whereas P450c17 and CytB5 were colocalized in the Leydig cells of the fetal testes, there was no immunostaining for either in the midgestational fetal ovary. Our findings of colocalization of CytB5 and P450c17 are strongly supportive of the view that CytB5 plays an important role in the regulation of the androgen biosynthetic pathway in the fetal and adult human.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 83-88 |
| Number of pages | 6 |
| Journal | Biology of Reproduction |
| Volume | 71 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 2004 |
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Keywords
- Adrenal cortex
- Aging
- Leydig cells
- Steroid hormones
- Theca cells
ASJC Scopus subject areas
- Cell Biology
- Developmental Biology
- Embryology
Cite this
Colocalization of P450c17 and cytochrome b5 in androgen-synthesizing tissues of the human. / Dharia, Sejal; Slane, Audry; Jian, Ming; Conner, Michael; Conley, Alan J; Parker, C. Richard.
In: Biology of Reproduction, Vol. 71, No. 1, 07.2004, p. 83-88.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Colocalization of P450c17 and cytochrome b5 in androgen-synthesizing tissues of the human
AU - Dharia, Sejal
AU - Slane, Audry
AU - Jian, Ming
AU - Conner, Michael
AU - Conley, Alan J
AU - Parker, C. Richard
PY - 2004/7
Y1 - 2004/7
N2 - Androgens are an integral part of human physiology. The de novo production of androgens is generally limited to the adrenal cortex and the gonads. Androgen synthesis by these steroidogenic tissues requires the bifunctional enzyme cytochrome P450c17, which catalyzes both 17 hydroxylase and 17,20 lyase activities. 17,20-lyase activity is relevant to the regulation of androgen production, and is allosterically modulated through the action of an accessory protein, cytochrome b5 (CytB5). Our objective was to determine the cellular localization of P450c17 and CytB5 in androgen-synthesizing tissues of the human. Immunohistochemical analyses of P450c17 and CytB5 were performed on fetal and adult human adrenals, ovaries, and testes. In the fetal adrenal, CytB5 and P450c17 were both found in the cells of the fetal zone, but not in the neocortex. In the adult adrenal, the zona fasciculata was immunoreactive for P450c17 only, whereas the zona reticularis was immunopositive for both P450c17 and CytB5. In the adult gonads, P450c17 and CytB5 were colocalized in the Leydig cells of the testis, theca interna cells of the follicle, theca lutein cells, and isolated cell clusters in the ovarian stroma. Whereas P450c17 and CytB5 were colocalized in the Leydig cells of the fetal testes, there was no immunostaining for either in the midgestational fetal ovary. Our findings of colocalization of CytB5 and P450c17 are strongly supportive of the view that CytB5 plays an important role in the regulation of the androgen biosynthetic pathway in the fetal and adult human.
AB - Androgens are an integral part of human physiology. The de novo production of androgens is generally limited to the adrenal cortex and the gonads. Androgen synthesis by these steroidogenic tissues requires the bifunctional enzyme cytochrome P450c17, which catalyzes both 17 hydroxylase and 17,20 lyase activities. 17,20-lyase activity is relevant to the regulation of androgen production, and is allosterically modulated through the action of an accessory protein, cytochrome b5 (CytB5). Our objective was to determine the cellular localization of P450c17 and CytB5 in androgen-synthesizing tissues of the human. Immunohistochemical analyses of P450c17 and CytB5 were performed on fetal and adult human adrenals, ovaries, and testes. In the fetal adrenal, CytB5 and P450c17 were both found in the cells of the fetal zone, but not in the neocortex. In the adult adrenal, the zona fasciculata was immunoreactive for P450c17 only, whereas the zona reticularis was immunopositive for both P450c17 and CytB5. In the adult gonads, P450c17 and CytB5 were colocalized in the Leydig cells of the testis, theca interna cells of the follicle, theca lutein cells, and isolated cell clusters in the ovarian stroma. Whereas P450c17 and CytB5 were colocalized in the Leydig cells of the fetal testes, there was no immunostaining for either in the midgestational fetal ovary. Our findings of colocalization of CytB5 and P450c17 are strongly supportive of the view that CytB5 plays an important role in the regulation of the androgen biosynthetic pathway in the fetal and adult human.
KW - Adrenal cortex
KW - Aging
KW - Leydig cells
KW - Steroid hormones
KW - Theca cells
UR - http://www.scopus.com/inward/record.url?scp=3142657279&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3142657279&partnerID=8YFLogxK
U2 - 10.1095/biolreprod.103.026732
DO - 10.1095/biolreprod.103.026732
M3 - Article
C2 - 14985252
AN - SCOPUS:3142657279
VL - 71
SP - 83
EP - 88
JO - Biology of Reproduction
JF - Biology of Reproduction
SN - 0006-3363
IS - 1
ER -