Biology Reference
In-Depth Information
instrument response time from spectroscopic data (Jansson [1984]). In
spectroscopy applications, the data are usually very accurate, with a
much lower measurement uncertainty than the hormone concentration
time series. In addition, spectroscopic applications will typically have
many more data points and will not contain either outliers or missing
values. Thus, the assumptions that are inherent in these methods may
not be valid for hormone concentration time series data, where the
experimental uncertainties (i.e., measurement errors) are substantially
larger and variable and missing values and outliers are common.
A. Convolution Integral Model
This method is based on the assumption that the observed time
dependence of the hormone concentration, C(t), in the blood results from
the coupling of two opposing physiological mechanisms—the rate of
secretion, S(t), into the blood and elimination, E(t), from the blood, as
shown in Figure 9-18. In Chapter 1, we explored a similar dependence in
the context of designing optimal drug intake regimens. We examined the
concentration of the drug in the bloodstream resulting from multiple
doses administered at equal time intervals and discussed how
physiological elimination affects the concentration.
Hormone concentrations in the blood are controlled by the same
competing mechanisms. When the hormone is secreted by the endocrine
glands, its concentration in the blood increases. Simultaneously, the
pharmacokinetic processes eliminating the hormone from the blood are
working to decrease its concentration. Thus, serum hormone
concentration data cannot be used directly for assessing the hormone
secretion. To obtain detailed information about the secretion events, the
processes of basal secretion and the pharmacokinetic elimination must
be decoupled. In other words, given the concentration function C(t) and
the elimination function E(t), can the rate of secretion S(t) be recreated?
Figure 9-19 provides a depiction of the coupling between secretion and
elimination similar to Figure 1-25 of Chapter 1. The difference here is
that we do not assume an instantaneous increase in concentration. The
top panel of Figure 9-19 shows a typical secretion event (i.e., the rate of
S
(
t
)
E
(
t
)
C
(
t
)
&
Time
Time
Time
FIGURE 9-18.
Concentration results from the coupling of the secretion and the elimination. (From Veldhuis, J.D.,
Carlson, M.L. & Johnson, M.L. [1987]. The pituitary gland secretes in bursts: Appraising the nature of
glandular secretory impulses by simultaneous multiple-parameter deconvolution of plasma hormone
concentrations. Proceedings of the National Academy of Sciences of the United States of America, 84,
7686-7690.)
