Hypothalamus System

GnRH is chosen as the starting point for describing the estrus cycle. After its synthesis and release GnRH is transported from the hypothalamus to the

Fig. 7. Schematic overview of the estrus cycle model. Each compartment is characterized by physiological and biochemical parameters. There is a blood flow to each tissue (as a fraction of the total blood flow). The abbreviations of the hormone names (GnRH,Dop,E2, P, LH,FSH, PRL, and Inh) indicate in which tissues they are synthesized and where they exert their positive (+) or negative (-) feedback on the endocrine system

Fig. 7. Schematic overview of the estrus cycle model. Each compartment is characterized by physiological and biochemical parameters. There is a blood flow to each tissue (as a fraction of the total blood flow). The abbreviations of the hormone names (GnRH,Dop,E2, P, LH,FSH, PRL, and Inh) indicate in which tissues they are synthesized and where they exert their positive (+) or negative (-) feedback on the endocrine system pituitary via the hypophysial portal veins where it stimulates the release of LH and FSH. Even though in vivo GnRH is excreted in a pulsatile way, this model assumes a constant signal produced by the intrinsic rhythm of the GnRH cells [65-67]. On the level of the hypothalamus, free E2 increases the synthesis of GnRH by receptor activation, and a partial agonist (PA) can compete with this free E2 for its receptor. The partial transcriptional activation of the estrogen receptor by the endocrine disrupter is described by the weighing term w.

Cumulative exposure to E2 causes aging of the neuronal network of the hypothalamus, resulting in a decrease of its intrinsic signal [68] and modeled as a degradation of the synthesis rate. This can eventually lead to insufficient GnRH signaling to the pituitary. A second signal that originates in the hypothalamus is the neurotransmitter, annex hormone, dopamine (Dop), which is considered to be the predominant inhibiting factor for prolactin (PRL) synthesis [69].

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