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Cell culture of granulosa cells can be performed in vitro. Plating density (number of cells per volume of culture medium) plays a critical role for the differentiation. A lower plating density makes granulosa cells exhibit estrogen production, while a higher plating density makes them appear as progesterone producing theca lutein cells. [12]
The anterior pituitary complex and hypophyseal portal system, where FSH and LH are released. Theca cells are responsible for synthesizing androgens, providing signal transduction between granulosa cells and oocytes during development by the establishment of a vascular system, providing nutrients, and providing structure and support to the follicle as it matures.
The granulosa lutein cells do have aromatase, and use it to produce estrogens, using the androgens previously synthesized by the theca lutein cells, as the granulosa lutein cells in themselves do not have the 17α-hydroxylase or 17,20 lyase to produce androgens. [5] Once the corpus luteum regresses the remnant is known as corpus albicans. [12]
Theca interna cells express receptors for luteinizing hormone (LH) to produce androstenedione, which via a few steps, gives the granulosa the precursor for estrogen manufacturing. [1] After rupture of the mature ovarian follicle, the theca interna cells differentiate into the theca lutein cells of the corpus luteum.
Each type of cell behaves differently in response to FSH. Theca interna cells express receptors for luteinizing hormone . LH induces the production of androgens by the theca cells, most notably androstendione, which are aromatized by granulosa cells to produce estrogens, primarily estradiol. Consequently, estrogen levels begin to rise.
FSH stimulates the secretion of inhibin from the granulosa cells of the ovarian follicles in the ovaries. In turn, inhibin suppresses FSH. Inhibin B reaches a peak in the early- to mid-follicular phase, and a second peak at ovulation. Inhibin A reaches its peak in the mid-luteal phase.
The enzyme aromatase can be found in many tissues including gonads (granulosa cells), brain, adipose tissue, placenta, blood vessels, skin, and bone, as well as in tissue of endometriosis, uterine fibroids, breast cancer, and endometrial cancer. [citation needed] It is an important factor in sexual development.
FSH induces the proliferation of granulosa cells in the developing follicles, and the expression of luteinizing hormone (LH) receptors on these granulosa cells (Figure 1). Under the influence of FSH, aromatase and p450 enzymes are activated, causing the granulosa cells to begin to secrete estrogen.