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Modeling endocrine control of the pituitary-ovarian axis: androgenic influence and chaotic dynamics. Hendrix, Angelean O Hughes, Claude L Selgrade, James F 2018-06-04T14:27:10Z 2018-06-04T14:27:10Z 2014-01
dc.identifier.issn 0092-8240
dc.identifier.issn 1522-9602
dc.description.abstract Mathematical models of the hypothalamus-pituitary-ovarian axis in women were first developed by Schlosser and Selgrade in 1999, with subsequent models of Harris-Clark et al. (Bull. Math. Biol. 65(1):157-173, 2003) and Pasteur and Selgrade (Understanding the dynamics of biological systems: lessons learned from integrative systems biology, Springer, London, pp. 38-58, 2011). These models produce periodic in-silico representation of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), progesterone (P4), inhibin A (InhA), and inhibin B (InhB). Polycystic ovarian syndrome (PCOS), a leading cause of cycle irregularities, is seen as primarily a hyper-androgenic disorder. Therefore, including androgens into the model is necessary to produce simulations relevant to women with PCOS. Because testosterone (T) is the dominant female androgen, we focus our efforts on modeling pituitary feedback and inter-ovarian follicular growth properties as functions of circulating total T levels. Optimized parameters simultaneously simulate LH, FSH, E2, P4, InhA, and InhB levels of Welt et al. (J. Clin. Endocrinol. Metab. 84(1):105-111, 1999) and total T levels of Sinha-Hikim et al. (J. Clin. Endocrinol. Metab. 83(4):1312-1318, 1998). The resulting model is a system of 16 ordinary differential equations, with at least one stable periodic solution. Maciel et al. (J. Clin. Endocrinol. Metab. 89(11):5321-5327, 2004) hypothesized that retarded early follicle growth resulting in "stockpiling" of preantral follicles contributes to PCOS etiology. We present our investigations of this hypothesis and show that varying a follicular growth parameter produces preantral stockpiling and a period-doubling cascade resulting in apparent chaotic menstrual cycle behavior. The new model may allow investigators to study possible interventions returning acyclic patients to regular cycles and guide developments of individualized treatments for PCOS patients.
dc.language eng
dc.publisher Springer Science and Business Media LLC
dc.relation.ispartof Bulletin of mathematical biology
dc.relation.isversionof 10.1007/s11538-013-9913-7
dc.subject Ovary
dc.subject Ovarian Follicle
dc.subject Hypothalamo-Hypophyseal System
dc.subject Humans
dc.subject Polycystic Ovary Syndrome
dc.subject Follicle Stimulating Hormone
dc.subject Luteinizing Hormone
dc.subject Androgens
dc.subject Systems Biology
dc.subject Menstrual Cycle
dc.subject Nonlinear Dynamics
dc.subject Models, Biological
dc.subject Computer Simulation
dc.subject Female
dc.subject Mathematical Concepts
dc.subject Feedback, Physiological
dc.title Modeling endocrine control of the pituitary-ovarian axis: androgenic influence and chaotic dynamics.
dc.type Journal article Hughes, Claude L|0069970 2018-06-04T14:27:00Z
pubs.issue 1
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Obstetrics and Gynecology
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 76
duke.contributor.orcid Hughes, Claude L|0000-0001-5178-2258

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