Theca cells and neighboring granulosa cells
The ovary is composed of two cellular structures according with two cell-two gonadotrophin theory and is stimulated self by LH and FSH for processing ovarian steriodogenesis. (http://herkules.oulu.fi/isbn9514266676/html/i268160.html).
Theca cells and neighboring granulosa cells play vital role as there co-coordinately timed function make steriodogenesis dependent. (paper 4).
Theca cells are the main productive region for androgen where as cells from the granulosa region produces estradiol and estrone by utilizing testosterone and androstenedione respectively. (paper-2).
It has been hypothesized for c-fos producing different results of ovarian steriodogenesis in theca and granulosa compartments by distinctive character of the activator protein-1(AP-1) transcriptor factor.
The central hypothesis of the paper suggests that the main function of the c-fos is by inhibiting 17α-hydroxylase 17, 20 lyase (CYP 17) in granulosa cells, this leads to termination or suppression of androgendione (A4) synthesis. (paper -4)
Hence, stimulation of A4 production is seen as result, by an increase in levels of CYP17 in granulosa cell from the result of inhibiting c-fos activity. So, c-fos activity plays major role in stimulating A4 production.
The protein kinase A (PKA), protein kinase C (PKC) and MAPK pathways in different studies play vital role in granulosa cell steriodogenesis. (http://joe.endocrinology-journals.org/cgi/content/full/186/1/85).
The paper depicts the findings for the role of C-fos production and inhibited MAPK pathway and c-fos levels are appropriately measured. C-fos levels reduces when MAPK pathway inhibition takes place. C-fos depends upon MAPK pathway that helps in regulating its function and expression. (paper 24, 27)
The role of MAPK pathway inhibition on C-fos production is examined and found that if MAPK pathway is inhibited, this would result in decrease in the c-fos levels. This decrease in the c-fos levels resulted in uncontrolled CYP17 production and followed by continuous production of A4 by granulosa cell.
The paper suggests that MAPK pathway may be categorized as one of the mechanism regulator for inhibition of CYP 17 production in granulosa cell.
The findings of this study depict the role of c-fos in theca cells. To confirm the involvement of c-fos different experimental studies various studies performed.
In gene silencing experiments, C-fos and CYP-17 transcript levels are notified and examined before and after silencing and found that due to C-fos silencing there is significant increase in CYP 17 production in the granulosa cell.
Significant staining of C-fos indicated by immunohistochemistry studies in the granulosa cell layer but when compare with CYP-17 no demonstration of staining.
On the other hand positive staining for CYP-17 in theca cells and no evidence of staining found for C-fos.
HGL5 cells are treated with MAPK kinase inhibitor PD98059 that proceeded to 11 times increase in CYP17 mRNA levels as per results findings.
On the other hand, CYP17 mRNA levels increased by 8 times in c-fos gene silenced cells and androstenedione production increased by 13 times when treated with PD 98059.
Different sex steroids such as estrogen, progesterone and androgens are originated from human ovaries.
During the menstrual cycle the morphology of ovary changes from follicular to luteal phase and in addition, in the process of ovarian follicular development, many recent invitro studies show gonadal steroids as regulators in this development process. ( http://www.ncbi.nlm.nih.gov/pubmed/19389255).
So in order for core understanding of ovarian sex-steroid metabolism, localization of sites that specifies gonadal steroid production is very necessary that is to mark or indicate which cell types produce what type of steroid hormones.(paper-17).
This important finding helps in evaluating steroid hormone formation of functioning disorders related to ovary because these ovarian lesions are usually in relation with very complicated structural findings.
P450sec (side chain cleavage), 3β-HSD( hydroxysteroid dehydrogenase), P450C17(17α- hydroxylase) and P450 arom(aromatase) are four enzymes characterized in ovarian steriodogenesis. (steriodogenesis pdf).
In the process of steriodogenesis cells are usually blended with distinguishing feature of cell organelle that includes smooth endoplasmic reticulum and mitochondria.