O the high rate and this change is not the 'positiveO the high rate and

O the high rate and this change is not the “positive
O the high rate and this change is not the “positive feedback” phenomenon, since the high GnRH secretion rate is stable and lasts several days, much longer than the ovulatory surge. During the lutheal phase, due to E and Pg exposure, hypothalamic ER and PgR are diminished until the estrogen exposure becomes undetectable. This change in hypothalamic Thonzonium (bromide) chemical information sensitivity to circulating estrogens shifts the GnRH secretion rate to the low secretion that causes rapid lutheolysis. On the pituitary level, gonadotropin secreting cells depend on GnRH action. Since the pituitary GnRHRs are increased during the follicular phase, increased GnRH secretion will maximally increase gonadotropin secretion until GnRHRs are spent and this partial downregulation of pituitary GnRHRs limits duration of the gonadotropin surge.Description of the proposed ovulatory cycle interpretation This description is based on phase plane patterns from Graphs 2 and 3. Since precise blood values of other ovulatory cycle hormones are not available, the model is deliberately simplified to involve only these four hormones, namely FSH with estrogen and LH with progesterone. This model also lacks possible influences of estrogen, progesterone and activins on sensitivity of the pituitary gland to GnRH probably via changing the number of pituitary GnRH receptors. Nevertheless, all omitted plausible or possible interactions are not expected to contradict the here proposed simplistic model. In fact, it is expected that actions of in the model omitted hormones are not important for theTable 2 The proposed interpretation of ligand interactions with their receptorsLigand exposure no ligands Changes in receptor availability ER availability increased PgR availability scarce Consequence of sustained ligand exposure increased sensitivity to estrogen and reduced to progesterone due to lack of estrogen action estrogen action enhances progesterone sensitivity due to increased PgR expression prolonged exposure to progesterone reduces sensitivity both to estrogen and progesterone due to reduced ER receptor synthesis that diminishes estrogen action and thus reduces PgR expressiononly ER ligandsnormal or decreasedincreasedonly progesterone ER ligands progesteronedecreaseddecreasedEstrogen action on estrogen receptors (ER) is variable and acts as a prerequisite of progesterone receptor (PgR) expression. On the other hand, the progesterone actions are inherently limited, since sustained progesterone binding reduces both PgR and ER availability, leading to reduced sensitivity both to estrogen and progesterone.Kurbel Theoretical Biology and Medical Modelling 2012, 9:35 http://www.tbiomed.com/content/9/1/Page 9 ofproposed mechanisms that explain the gonadotropin PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28607003 surge and lutheolysis, based on these three key relations: ?Hypothalamic GnRH secretion is increased under estrogen exposure during two weeks that start before the ovulatory surge and lasts till lutheolysis. ?The pituitary GnRH receptors are so prone to downregulation through ligand binding that this must be important for their function. ?In several estrogen target tissues, PgR expression depends on previous estrogen binding to functional ERs, while Pg binding to the expressed PgRs reduces both ER and PgR expression.The follicular phaseDuring the first four days (days of PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26266977 menstrual bleeding), the pool of estrogen binding proteins slowly releases estrogen accumulated from the previous cycle. In the next days, levels of inhibin, E and Pg are low, allowing.