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https://hdl.handle.net/1959.11/49205
Title: | Modeling the Male Reproductive Endocrine Axis: Potential Role for a Delay Mechanism in the Inhibitory Action of Gonadal Steroids on GnRH Pulse Frequency |
Contributor(s): | Ferasyi, Teuku R (author); Barrett, P Hugh R (author) ; Blache, Dominique (author); Martin, Graeme B (author) |
Publication Date: | 2016-05-01 |
Early Online Version: | 2016-02-24 |
Open Access: | Yes |
DOI: | 10.1210/en.2015-1913![Open Access Link](/web/OA.png) |
Handle Link: | https://hdl.handle.net/1959.11/49205 |
Abstract: | | We developed a compartmental model so we could test mechanistic concepts in the control of the male reproductive endocrine axis. Using SAAM II computer software and a bank of experimental data from male sheep, we began by modeling GnRH-LH feed-forward and LH-T feedback. A key assumption was that the primary control signal comes from a hypothetical neural network (the PULSAR) that emits a digital (pulsatile) signal of variable frequency that drives GnRH secretion in square wave-like pulses. This model produced endocrine profiles that matched experimental observations for the testis-intact animal and for changes in GnRH pulse frequency after castration and T replacement. In the second stage of the model development, we introduced a delay in the negative feedback caused by the aromatization of T to estradiol at the brain level, a concept supported by empirical observations. The simulations showed how changes in the process of aromatization could affect the response of the pulsatile signal to inhibition by steroid feedback. The sensitivity of the PULSAR to estradiol was a critical factor, but the most striking observation was the effect of time delays. With longer delays, there was a reduction in the rate of aromatization and therefore a decrease in local estradiol concentrations, and the outcome was multiple-pulse events in the secretion of GnRH/LH, reflecting experimental observations. In conclusion, our model successfully emulates the GnRH-LH-T-GnRH loop, accommodates a pivotal role for central aromatization in negative feedback, and suggests that time delays in negative feedback are an important aspect of the control of GnRH pulse frequency.
Publication Type: | Journal Article |
Source of Publication: | Endocrinology, 157(5), p. 2080-2092 |
Publisher: | Oxford University Press |
Place of Publication: | United States of America |
ISSN: | 1945-7170 0013-7227 |
Fields of Research (FoR) 2020: | 310910 Animal physiology - systems |
Socio-Economic Objective (SEO) 2020: | 100412 Sheep for meat 100413 Sheep for wool |
Peer Reviewed: | Yes |
HERDC Category Description: | C1 Refereed Article in a Scholarly Journal |
Appears in Collections: | Journal Article
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