Kiek,
Zou jij svp uitleg kunnen geven/reageren op dit nieuw onderzoek van Fitzgerald?
Het heeft ook te maken met calcium maar hierin wordt ook over TSH/Ft4 setpoint model gesproken.
NB - Een van zijn laatste onderzoeken betreft dit:
Over schildklierregulatie / setpointmodel / fysiologie
viewtopic.php?t=2339
Nieuw onderzoek van Fitzgerald
Population data indicate that thyroid regulation is consistent with an equilibrium-point model, but not with a set-point model
Vertaald =
Bevolkingsgegevens geven aan dat schildklierregulatie consistent is met een evenwichtspuntmodel, maar niet met een instelmodel
https://acems.org.au/acems-publications ... oint-model
1 van de alinea's vertaald met Google translate:
Merk op dat deze relatie het tegenovergestelde is van hoe meer vertrouwde relatie van hogere FT4-waarden die geassocieerd zijn
met lagere TSH-waarden.
Deze laatste relatie weerspiegelt een compenserende proces en treedt op in een individu wanneer de FT4-waarde wordt verhoogd van een bepaald niveau als gevolg van veranderingen in de schildklier of het FT4-metabolisme (Dietrich et al. 2012; Leow en Goede 2014).
Dit is een andere fenomeen tot een stijging van het FT4-niveau veroorzaakt door een stijging van het TSH-niveau. Beide mechanismen voor het verhogen van FT4 bestaan in de fysiologie van de schildklier en er treden analoge processen op in andere endocriene systemen (Foresta et al. 1997; Andersen et al. 2002; Fliers et al. 2014).
Het is in feite de manipulatie van de TSH-reactie op FT4 waarop een beroep wordt gedaan het fenomeen van een aanpassing aan de FT4-set uitleggen punt (Fliers et al. 2014).
Het feit dat het bereiken van een het initiële setpoint moet ook een dergelijke manipulatie van TSH is erkend (Goede et al. 2014; Leow en
Goede 2014), maar het lijkt erop dat wij als eersten dit herkenden hoe een dergelijke manipulatie, indien aanwezig, van invloed moet zijn op de bevolking correlaties (Fitzgerald et al. 2017).
Origineel
Note that this relationship is the opposite of the more familiar relationship of higher FT4 values being associated
with lower TSH values.
This latter relationship reflects a compensatory process and occurs in an individual when the FT4 value is raised from a given level as a result of changes to the thyroid gland or FT4 metabolism (Dietrich et al. 2012; Leow and Goede 2014).
This is a different phenomenon to a rise in the FT4 level being caused by a rise in the TSH level. Both mechanisms of raising FT4 exist in thyroid physiology and analogous processes occur in other endocrine systems (Foresta et al. 1997; Andersen et al. 2002; Fliers et al. 2014).
It is in fact the manipulation of the TSH response to FT4 which is involved to explain the phenomenon of an adjustment to the FT4 set
point (Fliers et al. 2014).
The fact that attainment of any initial set point must too involve such manipulation of TSH has been recognized (Goede et al. 2014; Leow and
Goede 2014), but it seems that we were the first to recognize how such manipulation, if present, must affect population correlations (Fitzgerald et al. 2017).
Een paar overige alinea's uit het onderzoek
Set‐point models imply that, in the normal range, levels of a parameter are independent of the organ/processes producing the parameter, these organs in a sense being “slaves” (Leow and Goede 2014) to the set point process. Thus, the level of FT4 in the body is controlled and set by the hypothalamus‐pituitary rather than by the thyroid gland, and the level of calcium is controlled and set by the parathyroid glands rather than by the effector responses in the bone, kidney, and gut.
The thyroid gland and the effector responses in the bone, kidney and gut in these two systems, act as directed by the hypothalamus‐pituitary and the parathyroid glands, respectively. Cannon proposed that the brain co‐ordinates body systems, with the aim of maintaining the goal values of key internal variables (Goldstein, 2009).
An alternative, not generally accepted, view regarding parameter regulation, is that parameter levels, rather than resulting from a set point, result simply from the balance of various homeostatic mechanisms at play (Partridge 1982; Romanovsky 2004). In this “equilibrium‐point model,” the level of the parameter has no particular meaning or connotation to the individual, and the interindividual variation in levels of a parameter results directly from interindividual variation in these homeostatic processes. (A set point too, results from a balance, but has the additional property that the balance is controlled so as to attain the target value. It is this additional property, an integral part of current teaching (Modell et al. 2015), which is the focus of this work).
In our previous work (Fitzgerald and Bean 2016), we mathematically analyzed thyroid homeostasis to clarify the difference between the curve describing (the line of best fit of) the population distribution of Free thyroxine/Thyroid Stimulating Hormone (FT4/TSH) levels (the “population curve”) and the curve describing the physiological suppression of TSH by FT4 in individuals
This work in turn was based on previous work showing that the ambient level of a parameter at steady state is such that it is at the intersection of the curves describing the components of the relevant feedback loops. Thus, in thyroid physiology FT4 is stimulated by TSH and TSH is inhibited by FT4. The ambient level of FT4 lies where the curves describing these two processes cross (Dietrich et al. 2012). For serum calcium levels the analogous point would be where the curves describing, the suppression of PTH by calcium, and the stimulation of calcium levels by PTH, cross (Fig. 1).
The prevailing teaching regarding homeostasis, and in particular endocrine homeostasis, includes the fundamental concept of a “set point,” which represents a target or optimum level defended by physiological control mechanisms.
Analogies for the description and teaching of this concept have included thermostats and cruise controls.
We previously demonstrated that such a set-point model of regulation implies that in population data of parameter set point/controlling hormone levels, correlations between the parameter and its controlling hormone must be in the direction of the response of the parameter to its
controlling hormone, and that in thyroid homeostasis this relationship is not observed.
In this work we similarly examined population correlations, extracted from the literature, for the parameters glucose and calcium, and their
controlling hormones.
We found 10 correlations. Most were highly significant (P < 0.01).
All were in the direction of the response of the controlling hormone to the parameter.
Therefore, none were consistent with the pattern implied by a set-point model of regulation. Instead all were consistent with an
“equilibrium point” model of regulation, whereby ambient levels have no particular connotation to the individual, and result passively from the interplay of physiological processes.
We conclude that glucose and calcium regulation,
like thyroid regulation, are not centered on set points.
This may reflect a general property of homeostasis.
We provide an alternative mechanistic analogy, without a set point, for the heuristic description and teaching, of homeostasis.
Figure 1
The negative feedback loop between a regulated parameter (e.g., FT4, calcium) and the respective controlling hormone (e.g., TSH, PTH). Panel {d} demonstrates that at equilibrium levels the two components of the feedback loop are solved simultaneously, as represented by the intersection point of the component curves. Different systems will differ in terms of the exact shapes of the component curves.
Figure 2
The extension of Figure 1{d}, demonstrating different individuals of a population attaining different levels of the same parameter, on account of interindividual variations in the components of the feedback loop leading to different intersection points. The red line indicates the derivation of a line of best fit, a “population curve.”
Table 1.
Summary of empiric correlations derived from the literature and expected correlations in set‐point models of regulation. NS = not significant
Artikel:
Funding Information
No funding information provided.
Received: 30 October 2017; Accepted: 28
November 2017
doi: 10.14814/phy2.13551
Physiol Rep, 6 (1), 2018, e13551,
https://doi.org/10.14814/phy2.13551
Correspondence
Stephen P. Fitzgerald, The Department of
General Medicine and The Department of
Endocrinology, The Royal Adelaide Hospital,
Port Road, Adelaide 5000, South Australia,
Link gehele artikel:
https://physoc.onlinelibrary.wiley.com/ ... phy2.13551
.