A mathematical model of prolactin secretion: Effects of dopamine and thyrotropin-releasing hormone

Prolactin (PRL) is secreted in a pulsatile manner by lactotroph cells in the anterior pituitary gland and displays a circadian rhythm as well as increases in response to stress, sexual intercourse, breast stimulation, and suckling. We propose a mathematical model of prolactin secretion which is mainly controlled by the inhibiting effect of dopamine (DA) and the stimulating effect of thyrotopin releasing hormone (TRH). By applying the singular perturbation technique, the conditions are derived under which our model exhibits a periodic solution corresponding to the normal secretory pattern of PRL which has been observed as a series of daily pulses, occurring every 2-3 hours. Numerical investigations also show that chaotic time series is admitted by our model which resembles irregular patterns observed in PRL concentration profiles of patients with microprolactinoma and macroprolactinoma. Explaining the conditions that delineate varying dynamic behavior in this nonlinear system in terms of the removal rates of the three state variables, the removal rate d"1 of TRH seems to play the most important role in identifying different physiological conditions.

[1]  Christopher Jones,et al.  Geometric singular perturbation theory , 1995 .

[2]  M. Mori,et al.  Prolactin secretion in mice with thyrotropin-releasing hormone deficiency. , 2006, Endocrinology.

[3]  N. Ben-Jonathan,et al.  Dopamine as a prolactin (PRL) inhibitor. , 2001, Endocrine reviews.

[4]  M. Freeman,et al.  Decreased expression of fos-related antigens (FRAs) in the hypothalamic dopaminergic neurons after immunoneutralization of endogenous prolactin , 2001, Endocrine.

[5]  Steven M. Pincus,et al.  Increased episodic release and disorderliness of prolactin secretion in both micro- and macroprolactinomas. , 1999, European journal of endocrinology.

[6]  J. Gross,et al.  Prolactin and growth hormone secretion after thyrotrophin-releasing hormone infusion and dopaminergic (DA2) blockade in infertile patients with minimal/mild endometriosis. , 2002, Human reproduction.

[7]  P. Lledo,et al.  Evidence that TRH controls prolactin release from rat lactotrophs by stimulating a calcium influx , 1994, Cell Biology and Toxicology.

[8]  H. Maurice Goodman,et al.  Basic Medical Endocrinology , 2003 .

[9]  R. Baron,et al.  Osteoblasts Are a New Target for Prolactin: Analysis of Bone Formation in Prolactin Receptor Knockout Mice* *This work was supported in part by grants from Hoechst Marion Roussel, Inc. , 1999, Endocrinology.

[10]  Chontita Rattanakul,et al.  Modeling of bone formation and resorption mediated by parathyroid hormone: response to estrogen/PTH therapy. , 2003, Bio Systems.

[11]  M. Low,et al.  Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms. , 2002, The Journal of clinical investigation.

[12]  R. Bertram,et al.  Rhythmic secretion of prolactin in rats: action of oxytocin coordinated by vasoactive intestinal polypeptide of suprachiasmatic nucleus origin. , 2004, Endocrinology.

[13]  G. Nagy,et al.  Immunoneutralization of prolactin prevents stimulatory feedback of prolactin on hypothalamic neuroendocrine dopaminergic neurons , 2000, Endocrine.

[14]  S. Ruktamatakul,et al.  Modeling insulin kinetics: responses to a single oral glucose administration or ambulatory-fed conditions. , 2001, Bio Systems.

[15]  Shu-Chuan Yang,et al.  Effects of prolactin-releasing peptide on tuberoinfundibular dopaminergic neuronal activity and prolactin secretion in estrogen-treated female rats. , 2002, Journal of biomedical science.

[16]  M. J. Evans,et al.  Inter‐Relationships Between the Secretory Dynamics of Thyrotrophin‐Releasing Hormone, Thyrotrophin and Prolactin in Periovulatory Mares: Effect of Hypothyroidism , 2004, Journal of neuroendocrinology.

[17]  K. Tasaka,et al.  Effects of thyrotropin-releasing hormone and phorbol ester on dopamine release from dispersed rat tuberoinfundibular dopaminergic neurons , 1993, Peptides.

[18]  R. E. Blackwell.  Hyperprolactinemia. Evaluation and management. , 1992, Endocrinology and metabolism clinics of North America.

[19]  G. Nagy,et al.  Prolactin: structure, function, and regulation of secretion. , 2000, Physiological reviews.

[20]  Sergio Rinaldi,et al.  Low- and high-frequency oscillations in three-dimensional food chain systems , 1992 .