This pattern of granulosa cell proliferation and differentiation that characterizes the natural growth of follicles can be mimicked in hypophysectomized rats by a specific hormonal regimen. Injections of estradiol (1.5 mg for 3 days) followed by FSH (1.0 ^g for 2 days) stimulate granulosa cell proliferation and follicle growth to the preovulatory stage. A subsequent ovulatory dose of hCG (10 IU) triggers ovulation and luteinization.
In the hypophy-sectomized rat, as well as in mutant mice lacking either gonadotropins (hypogonadal ) or FSH, follicular development is arrested at the preantral stage (Fig. 2). Mice lacking estrogen receptor a (ERa) also exhibit impaired follicular growth and infertility, but the follicles develop to the antral stage presumably due to the presence of estrogen receptor (3 (ERp) in these cells. These models illustrate that although the early, slow stages of granulosa cell proliferation and preantral follicle growth occur in the absence of gonadotropins and estradiol, these hormones (and their receptors) are required for normal growth—especlallythefinalrapid stagesofdevelopment that form preovulatory follicles and permit these cells to luteinize. flovent inhaler
FIG. 2. Schematic of ovarian follicular development and models that disrupt this process. Granulosa cell proliferation leads to follicular growth and the formation of large preovulatory follicles. LH triggers ovulation and the formation of corpora lu-tea. Hypophysectomized rats, as well as mice null for GnRH (hypogonadal), FSHp subunit, and cyclin D2, exhibit impaired follicular growth with follicles arrested at the preantral stage of growth. Mice null for ERa, but not ERp, have antral follicles that do not ovulate or luteinize. Mice lacking p27Kip1 exhibit abnormal corpus lu-teum formation.