Ovaries

Recruitment and maturation of follicles, ovulation on the day of estrus and the differentiation of follicular-tissue into luteal tissue [76-78] is controlled by an interplay of neuronal and hormonal control mechanisms situated in the pituitary and central nervous system. Follicle cohorts need four cycles to grow to a size large enough to sustain the estrus cycle [79], and individual follicles (consisting of both theca and granulosa cells) are assumed to follow exponential growth kinetics under the influence of FSH. After ovulation, occurring as a result of a LH surge, the follicular tissue starts differentiating to luteal tissue and simultaneously degenerates.

As the follicles grow, they start producing amounts of E2 and inhibin (Inh). P is synthesized by the granulosa cells during proestrus and its peak is assumed to be controlled by the proestrus surge of LH [80]. The second P peak that occurs during the afternoon of metestrus arises from the newly formed corpora lutea (CL) [81]. Finally, simple first-order kinetics describe E2 and P degradation in the liver. GnRH, LH, FSH, PRL, Inh, and Dop are degraded in the blood using first order kinetics.

The next step would be trying to enhance the model, including possible signaling pathways, other tissues involved in endocrine and estrogen signaling, or linking it with a multistage cancer model. There seem to be numerous possibilities but also just as many data requirements.

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